WorldWideScience

Sample records for engineered drug therapies

  1. Engineered nanoparticles for drug delivery in cancer therapy.

    Science.gov (United States)

    Sun, Tianmeng; Zhang, Yu Shrike; Pang, Bo; Hyun, Dong Choon; Yang, Miaoxin; Xia, Younan

    2014-11-10

    In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Non-genetic engineering of cells for drug delivery and cell-based therapy.

    Science.gov (United States)

    Wang, Qun; Cheng, Hao; Peng, Haisheng; Zhou, Hao; Li, Peter Y; Langer, Robert

    2015-08-30

    Cell-based therapy is a promising modality to address many unmet medical needs. In addition to genetic engineering, material-based, biochemical, and physical science-based approaches have emerged as novel approaches to modify cells. Non-genetic engineering of cells has been applied in delivering therapeutics to tissues, homing of cells to the bone marrow or inflammatory tissues, cancer imaging, immunotherapy, and remotely controlling cellular functions. This new strategy has unique advantages in disease therapy and is complementary to existing gene-based cell engineering approaches. A better understanding of cellular systems and different engineering methods will allow us to better exploit engineered cells in biomedicine. Here, we review non-genetic cell engineering techniques and applications of engineered cells, discuss the pros and cons of different methods, and provide our perspectives on future research directions. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Genetically engineered bifidobacterium as a drug delivery system for systemic therapy of metastatic breast cancer patients.

    Science.gov (United States)

    Fujimori, Minoru

    2006-01-01

    A fundamental obstacle in systemic therapy for metastatic breast cancer patients is specific targeting of therapy directly to a solid tumor. Hypoxic or necrotic regions are characteristic of solid tumors in many murine and human tumors, including the majority of primary tumors of the breast. A strain of anaerobic bacteria such as Bifidobacterium or Clostridium selectively localizes to and proliferates in solid tumors after systemic application. Another approach uses attenuated Salmonella strains that need tumor-specific nutrients to selectively proliferate and is a potential gene delivery system. We constructed a plasmid, pBLES100-S-eCD, which included the cytosine deaminase gene. Transfected Bifidobacterium longum produced cytosine deaminase in the hypoxic tumor. Enzyme/pro-drug therapy was confirmed to be effective for systemic administration.

  4. Biotechnology and genetic engineering in the new drug development. Part II. Monoclonal antibodies, modern vaccines and gene therapy.

    Science.gov (United States)

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Monoclonal antibodies, modern vaccines and gene therapy have become a major field in modern biotechnology, especially in the area of human health and fascinating developments achieved in the past decades are impressive examples of an interdisciplinary interplay between medicine, biology and engineering. Among the classical products from cells one can find viral vaccines, monoclonal antibodies, and interferons, as well as recombinant therapeutic proteins. Gene therapy opens up challenging new areas. In this review, a definitions of these processes are given and fields of application and products, as well as the future prospects, are discussed.

  5. Fetal drug therapy.

    OpenAIRE

    Evans, M I; Pryde, P G; Reichler, A; Bardicef, M; Johnson, M P

    1993-01-01

    Fetal drug therapy encompasses several areas, including the prevention of external genital masculinization in 21-hydroxylase deficiency syndrome (congenital adrenal hyperplasia), biochemical amelioration of methylmalonic acidemia, and biotin-responsive multiple carboxylase deficiency. The correction of cardiac arrhythmias has become relatively commonplace, and a reduction in the risks of neural tube defects is now possible with the use of preconceptual and early conceptual folic acid. Similar...

  6. Beginnings of drug therapy: drug therapy in ancient India.

    Science.gov (United States)

    Borchardt, John K

    2003-01-01

    Four thousand years ago, the medical knowledge of the Indian subcontinent was codified into a system called the Ayurveda. Ayurveda remains a vital system of medicine and drug therapy in India and elsewhere. Plant alkaloids are the primary active ingredients of Ayurvedic drugs. Today the pharmacologically active ingredients of many Ayurvedic medicines are being identified and their usefulness in drug therapy being determined. (c) 2003 Prous Science. All rights reserved.

  7. Algorithms for optimizing drug therapy

    Directory of Open Access Journals (Sweden)

    Martin Lene

    2004-07-01

    Full Text Available Abstract Background Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. Methods One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface and JavaScript (program logic. Results Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs

  8. Evaluation of drug therapy problems among renal patients receiving ...

    African Journals Online (AJOL)

    Conclusion: Drug therapy problems among renal patients were high. Inappropriate drug selection and drug interactions were the commonest drug therapy problems. The acceptance of pharmacists' interventions by prescribers was appreciable. Keywords: Drug therapy problems, Renal patients, Therapy, Intervention, ...

  9. Alternative Drugs in Pain Therapy

    Directory of Open Access Journals (Sweden)

    İlker Kelle

    2006-01-01

    Full Text Available Various treatment modalities of acute and chronic pain have been an area of interest of medicine and investigators for centuries. There are two major classes of drugs that are used to control pain: opioid and non-opioid analgesics. They could be used in the case of monotherapy or combination therapy in pain management. However, these agents are not accepted as ideal drugs in clinical approaches against pain because of their serious side effects such as development of tolerance and addiction, renal failure and gastrointestinal bleeding. As a consequent, developing new forms of pain relievers that are more safe and effective without any other side effects has became the main goal of researchers. In recent studies, it has been shown that conotoxin therapies are not addictive, and have tolerable indexes unlike opioids. In addition, conotoxins side effects are much milder and easier to manage than those of opioids. In this regard, it has been emphasized that biotoxins such as conotoxins obtained from marine creatures can be better choices in pain management for future prospects.

  10. Drug Transport and Pharmacokinetics for Chemical Engineers

    Science.gov (United States)

    Simon, Laurent; Kanneganti, Kumud; Kim, Kwang Seok

    2010-01-01

    Experiments in continuous-stirred vessels were proposed to introduce methods in pharmacokinetics and drug transport to chemical engineering students. The activities can be incorporated into the curriculum to illustrate fundamentals learned in the classroom. An appreciation for the role of pharmacokinetics in drug discovery will also be gained…

  11. Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2017-03-01

    Full Text Available Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.

  12. DRUG INTERACTIONS WITH TUBERCULOSIS THERAPY

    African Journals Online (AJOL)

    Kurt

    most relevant to tuberculosis drug interactions is drug metabolism, which is explained in more detail below. Drug metabolism interactions. Drugs are metabolised by two types of reactions: phase I reactions that involve oxi- dation, reduction or hydrolysis in which drugs are turned into more polar com- pounds, and phase II ...

  13. [Non-drug therapies for CRPS].

    Science.gov (United States)

    Krämer, H H; Tanislav, C; Birklein, F

    2012-06-01

    State of the art CRPS therapy comprises medication, interventional therapies and non-pharmaceutical treatments like physiotherapy (PT), occupational therapy, PT with cognitive behavioural elements (mirror therapy, 'motor imagery', and 'graded exposure'), psychotherapeutic methods, local therapies and neurostimulation. These treatments are mostly as successful as medical or interventional treatment. These effects have been demonstrated in small but randomised controlled studies. Adjuvant therapies were shown to reduce pain and the severity of dysfunction in CRPS. Therefore, these non-drug therapies should be an essential part of any multimodal CRPS treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  14. System engineering approach to planning anticancer therapies

    CERN Document Server

    Świerniak, Andrzej; Smieja, Jaroslaw; Puszynski, Krzysztof; Psiuk-Maksymowicz, Krzysztof

    2016-01-01

    This book focuses on the analysis of cancer dynamics and the mathematically based synthesis of anticancer therapy. It summarizes the current state-of-the-art in this field and clarifies common misconceptions about mathematical modeling in cancer. Additionally, it encourages closer cooperation between engineers, physicians and mathematicians by showing the clear benefits of this without stating unrealistic goals. Development of therapy protocols is realized from an engineering point of view, such as the search for a solution to a specific control-optimization problem. Since in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and antiangiogenic therapy to immunotherapy and gene therapy, but the class of models introduced is broad enough to incorporate other forms of therapy as well. The book be...

  15. [Drug interactions in pain therapy].

    Science.gov (United States)

    Syhr, K M J; Oertel, B G; Geisslinger, G

    2015-12-01

    Pain is one of the most common reasons for consulting a physician. Chronic pain patients often suffer from a variety of comorbidities, such as depression and anxiety and they are therefore often simultaneously treated with more than one drug. The probability of drug interactions increases with every additional drug. A systematic internet and literature search up to February 2015 was carried out. Systematic lists were included. In addition, the drug prescription information sheets were used and an internet search via Pubmed and google.com was carried out for drugs alone and in combination in order to find substance-specific interactions. A differentiation is made between pharmaceutical, pharmacodynamic and pharmacokinetic drug interactions. Pharmaceutical interactions are caused by chemical, physical or physicochemical incompatibility of drugs or adjuvants used. These can even occur outside the body and during concomitant administration via the same route. A pharmacodynamic interaction in pain management is for example the additive sedative effect of opioids and benzodiazepines when taken together. Pharmacokinetic interactions occur during the absorption, distribution, metabolism and in the elimination phases. Many drug interactions can be avoided by careful and continuous evaluation of pharmacotherapy and if necessary its adaptation; however, a sound knowledge of the underlying pharmacological mechanisms and the properties of currently used analgesics is necessary.

  16. Inhalable drugs for systemic therapy.

    Science.gov (United States)

    Corkery, K

    2000-07-01

    Although oral and injectable drug formulations still dominate the market, interest in pulmonary delivery has been rising steadily. Given patients' desire for an alternative to injections, and recent advances in aerosol science and pulmonary medicine, the potential for improved disease management outcomes by using aerosols for systemic drug delivery should lead the way for a shift to inhalables.

  17. Laboratory markers in personalized drug therapy

    NARCIS (Netherlands)

    Geerts, A.F.J.

    2012-01-01

    During the last decade two major trends have influenced the thinking about the benefit-risk balance in drug therapy.The first trend showed that this balance is not only determined by the interaction of the pharmacological properties of the drug with the patient’s (patho)physiological profile, but is

  18. Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

    Science.gov (United States)

    Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

    2017-01-20

    Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  19. Behaviour therapy for obesity treatment considering approved drug therapy.

    Science.gov (United States)

    Kossmann, Beate; Ulle, Tanja; Kahl, Kai G; Wasem, Jürgen; Aidelsburger, Pamela

    2008-05-29

    Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two), six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the interventions of media alone as well as through the intervention of

  20. Behaviour therapy for obesity treatment considering approved drug therapy

    Directory of Open Access Journals (Sweden)

    Wasem, Jürgen

    2008-05-01

    Full Text Available Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two, six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the

  1. [Pharmacogenetics and tailored drug therapy

    DEFF Research Database (Denmark)

    Nielsen, F.C.; Borregaard, N.

    2009-01-01

    Pharmacogenetics traditionally designates the study of genetically determined variation in metabolism of drugs and toxins from the environment. The concept of phamacogenetics has been widened to encompass how essential genetic alterations central to the development of diseases may by used to target...

  2. Artificial intelligence in drug combination therapy.

    Science.gov (United States)

    Tsigelny, Igor F

    2018-02-09

    Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Drug dosing during continuous renal replacement therapies.

    Science.gov (United States)

    Thompson, A Jill

    2008-04-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal function; all of these may change from patient to patient or even in the same patient depending on the clinical status. However, CRRT modalities are generally more efficient than intermittent hemodialysis at drug removal, in some cases approximating or even exceeding normal renal function, resulting in a significant risk of subtherapeutic dosing if conventional hemodialysis dosing recommendations are followed. This annotated bibliography provides a summary of publications analyzing drug removal during CRRT, including CRRT settings and drug clearance values found in each study. Caution is warranted as findings from one study may not be generalizable to all patients due to the many factors that influence drug removal. Serum drug concentrations should be monitored when available, and patient clinical status is exceedingly important for following expected and unexpected responses to drug therapies. Reviews on general drug dosing calculations in CRRT are available elsewhere.

  4. Drug Therapy in Obese Adolescents

    Directory of Open Access Journals (Sweden)

    Zinat Salem

    2013-03-01

    Full Text Available Background: The behavior and dietary treatments are not so successful for extremely obese adolescents. Therefore, using drugs to treat extremely obese children and adolescents are among the modern approaches. This research aims to study the pharmaceutical interventions performed for treatment of obese children. Materials and Methods: The strategy of research was using of key words ‘obesity’, ‘adolescence’, ‘treatment’ and ‘anti-obesity drugs’ were searched in websites of PubMed, Iranian Medical Digital Library, SID, Iran Medex, Magiran. This study reviewed all the available published papers in English and Farsi languages during 2000-2010. The Criteria for exclusion was The papers that had been published on interventions and treatment of eating disorders, type II diabetes or the obesity caused by the secondary syndromes. Results: Twelve papers were found as short-term clinical trials and/or long-term follow-ups. In these studies, the positive effects of ‘sibutramine’ in some studies are shown; although some other side effects are reported as well. A significant weight-loss had been reported on ‘orlistat’ medicine, but digestive complications had been observed as well. None of the studies had followed up patients for more than one year. Apparently, ‘Metformin’ requires further studies.Conclusion: The FDA has only approved ‘sibutramine’ and ‘orlistat’ drugs. But side effects of long-term these drugs have already been unknown. However, it seems that ‘orlistat’ is applied for ≥12-year-old children and ‘sibutramine’ for ≥ 16-year-old children.

  5. Drug therapy in the neonatal foal.

    Science.gov (United States)

    Baggot, J D

    1994-04-01

    The neonatal period in foals refers to the first 7 days of postnatal life. The effects of drugs (pharmacologic agents) may be different in neonatal foals, particularly during the first 3 days of postnatal life, from those in older foals and adult horses. The changed drug effects decrease as the physiologic processes that affect absorption, distribution, and elimination (metabolism and excretion) of drugs mature. Dosage regimens should take into account the altered pharmacokinetic profiles of drugs, and because of wide individual variation, the response to therapy should be closely monitored for signs of toxicity. In conjunction with the prudent use of drugs, good nursing care and the provision of supportive therapy are critical in the management of neonatal foal diseases. Over-crowding imposes stress upon young foals and predisposes them to an increased incidence of bacterial and parasitic infections. The collection of specimens for precise microbiologic diagnosis and correction of deficits in serum immunoglobulins should precede antimicrobial therapy. Although E. coli is by far the most common cause of bacterial infections in neonatal foals, other bacterial pathogens of unpredictable susceptibility often cause infection. The selection of an antimicrobial drug for specific therapy should be based on both the microbiologic (quantitative susceptibility) and pharmacologic (pharmacokinetic) properties of the drug. The use of an antimicrobial drug or combination of drugs that will produce a bactericidal effect is highly desirable. Whenever possible, a parenteral preparation that can be administered intravenously should be chosen. The bioavailability and selectivity of action of pharmacologic agents are influenced by the dosage form and route of administration. Diazepam is the sedative drug of choice for neonatal foals. Cimetidine, an H2-receptor antagonist, may be indicated in foals diagnosed to have gastric ulcers; hepatic microsomal oxidative metabolism of drugs

  6. Drug therapy for hereditary cancers

    Directory of Open Access Journals (Sweden)

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  7. Anticoagulation Drug Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Harter, Katherine

    2015-01-01

    Full Text Available Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter. [West J Emerg Med. 2015;16(1:11–17.

  8. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer Recruiting No Results Available NO Drug: Lapatinib|Drug: Herceptin ...Trastuzumab ( Herceptin ) -Refractory, Metastatic Breast Cancer Active, not recruiting No Results Available NO Drug: Capecitabine|Drug: Lapatinib Lapatinib...Lapatinib Plus Herceptin With or Without Endocrine Therapy Recruiting No Results Available NO Drug: Herceptin |Drug: Lapatinib|Drug: Letrozole

  9. PRINCIPLES OF DRUG THERAPY IN NEWBORNS

    Directory of Open Access Journals (Sweden)

    G.V. Yatsyk

    2011-01-01

    Full Text Available The article is devoted to the neonats adequate pharmacotherapy, including use of medications off-label. The authors emphasize the characteristics of a newborn child organism (as a full-term and preterm that define the distinct processes of pharmacokinetics and pharmacodynamics in the older children. This paper discusses the problem of the optimal route of administration choice, provides basic information about medications used in the most common pathological conditions in newborns. Key words: drug therapy, drugs, newborns, premature infants. (Pediatric pharmacology. — 2011; 8 (6: 50–56.

  10. Drug therapy for peripheral vestibular vertigo

    Directory of Open Access Journals (Sweden)

    L. M. Antonenko

    2017-01-01

    Full Text Available The choice of effective treatments for vestibular vertigo is one of the important problems, by taking into account the high prevalence of peripheral vestibular diseases. Different drugs, such as vestibular suppressants for the relief of acute vertigo attacks and vestibular compensation stimulants for rehabilitation treatment, are used to treat vestibular vertigo. Drug therapy in combination with vestibular exercises is effective in patients with vestibular neuronitis, Meniere's disease, so is that with therapeutic maneuvers in patients with benign paroxysmal positional vertigo. The high therapeutic efficacy and safety of betahistines permit their extensive use for the treatment of various vestibular disorders.

  11. Validation of GPU based TomoTherapy dose calculation engine.

    Science.gov (United States)

    Chen, Quan; Lu, Weiguo; Chen, Yu; Chen, Mingli; Henderson, Douglas; Sterpin, Edmond

    2012-04-01

    The graphic processing unit (GPU) based TomoTherapy convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic performance improvement over the traditional CPU-cluster based TomoTherapy dose engine (CPU dose engine). Besides the architecture difference between the GPU and CPU, there are several algorithm changes from the CPU dose engine to the GPU dose engine. These changes made the GPU dose slightly different from the CPU-cluster dose. In order for the commercial release of the GPU dose engine, its accuracy has to be validated. Thirty eight TomoTherapy phantom plans and 19 patient plans were calculated with both dose engines to evaluate the equivalency between the two dose engines. Gamma indices (Γ) were used for the equivalency evaluation. The GPU dose was further verified with the absolute point dose measurement with ion chamber and film measurements for phantom plans. Monte Carlo calculation was used as a reference for both dose engines in the accuracy evaluation in heterogeneous phantom and actual patients. The GPU dose engine showed excellent agreement with the current CPU dose engine. The majority of cases had over 99.99% of voxels with Γ(1%, 1 mm) GPU dose engine also showed similar degree of accuracy in heterogeneous media as the current TomoTherapy dose engine. It is verified and validated that the ultrafast TomoTherapy GPU dose engine can safely replace the existing TomoTherapy cluster based dose engine without degradation in dose accuracy.

  12. Drug Dosing During Continuous Renal Replacement Therapies

    OpenAIRE

    Thompson, A. Jill

    2008-01-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal func...

  13. Engineering AAV receptor footprints for gene therapy.

    Science.gov (United States)

    Madigan, Victoria J; Asokan, Aravind

    2016-06-01

    Adeno-associated viruses (AAV) are currently at the forefront of human gene therapy clinical trials as recombinant vectors. Significant progress has been made in elucidating the structure, biology and tropisms of different naturally occurring AAV isolates in the past decade. In particular, a spectrum of AAV capsid interactions with host receptors have been identified and characterized. These studies have enabled a better understanding of key determinants of AAV cell recognition and entry in different hosts. This knowledge is now being applied toward engineering new, lab-derived AAV capsids with favorable transduction profiles. The current review conveys a structural perspective of capsid-glycan interactions and provides a roadmap for generating synthetic strains by engineering AAV receptor footprints. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Gene therapy for cartilage and bone tissue engineering

    CERN Document Server

    Hu, Yu-Chen

    2014-01-01

    "Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

  15. Leishmaniasis in humans: drug or vaccine therapy?

    Science.gov (United States)

    Ghorbani, Masoud; Farhoudi, Ramin

    2018-01-01

    Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results. PMID:29317800

  16. [Drug therapy for benign prostatic syndrome (BPS)].

    Science.gov (United States)

    Berges, R

    2006-09-01

    Alpha1-receptor blockers (alfuzosin, doxazosin, tamsulosin and terazosin), 5alpha-reductase inhibitors (dutasteride and finasteride) and combinations thereof are used in the drug treatment of benign prostatic syndrome. As before, there is still no evidence supporting the use of plant extracts, the use of anticholinergic substances alone or in combination with other BPS drugs is currently under investigation and should not be attempted outside of clinical trials. For all drugs the placebo effect is considerable. Accordingly, deviations from the recommended doses are rapidly associated with an activity loss over that of placebo. alpha1-Receptor blockers show a rapid onset of action and are slightly superior to 5alpha-reductase inhibitors with regard to the relief of symptoms. All alpha1-receptor blockers are similarly effective at adequate doses, however, quantitative differences are seen in the side effect profiles. 5alpha-reductase inhibitors also provide relief from BPS-associated symptoms with the relief being volume-dependent. Prostate volume-dependent complications of BPS (operation risk and risk of acute urine retention) can be reduced by 5alpha-reductase inhibitors. Long-term drug studies have demonstrated the superiority of combination therapies over monotherapies with alpha1-receptor blockers and 5alpha-reductase inhibitors in patients with a high risk for progression. This superiority is accompanied by a combination of the respective side-effect profiles and their absolute increase. Besides poorer tolerability, combination therapies also result in higher costs. Thus, it is important to decide at an early stage which patients are to be treated with drugs and which by surgery.

  17. Assessing multiparametric drug response in tissue engineered tumor microenvironment models.

    Science.gov (United States)

    Harris, Alexandra R; Yuan, Jessica X; Munson, Jennifer M

    2017-12-16

    The tumor microenvironment is important in promoting treatment resistance of tumor cells via multiple mechanisms. However, studying this interaction often proves difficult. In vivo animal models are costly, time-consuming, and often fail to adequately predict human response to treatment. Conversely, testing drug response on human tumor cells in vitro in 2D cell culture excludes the important contribution of stromal cells and biophysical forces seen in the in vivo tumor microenvironment. Here, we present tissue-engineered models of both human brain and breast tumor microenvironments incorporating key stromal cell populations for assessing multiple mechanisms of therapeutic response using flow cytometry. We show our physiologically-relevant systems used to interrogate a variety of parameters associated with chemotherapeutic efficacy, including cell death, proliferation, drug uptake, and invasion of cancer and stromal cell populations. The use of flow cytometry allows for single cell, quantitative, and fast assessments of multiple outcomes affecting anti-tumor therapy failure. Our system can be modified to add and remove cellular components with ease, thereby enabling the study of individual cellular contributions in the tumor microenvironment. Together, our models and analysis methods illustrate the importance of developing fast, cost-effective, and reproducible methods to model complex human systems in a physiologically-relevant manner that may prove useful for drug screening efforts in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Drug Therapy for Heart Valve Diseases

    Science.gov (United States)

    Borer, Jeffrey S.; Sharma, Abhishek

    2015-01-01

    Valvular heart diseases (VHDs) are progressive. When not caused by acute comorbidities they are generally characterized by long asymptomatic phases during which hemodynamic severity may progress leading to morbidity and mortality. Treatment depends on VHD type and severity but when severe and symptomatic, usually involves mechanical intervention. Asymptomatic patients, and those who lack objective descriptors associated with high risk, are closely observed clinically with optimization of associated cardiovascular risk factors until surgical indications develop. Though often prescribed based on theory, no rigorous evidence supports pharmacological therapy in most chronic situations though drugs may be appropriate in acute valvular diseases, or as a bridge to surgery in severely decompensated patients. Herein, we examine evidence supporting drug use for chronic VHDs. PMID:26371236

  19. Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy

    Science.gov (United States)

    Dasgupta, Anindya; Shields, Jordan E.

    2012-01-01

    Abstract Multimodal therapy approaches, such as combining chemotherapy agents with cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector cells. Overcoming such toxic effects of anticancer cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of immunocompetent cells, thereby allowing for the coadministration of cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into immunocompetent cells. In the present study, we evaluated a DRI-based strategy that incorporates the immunocompetent cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector cells efficiently lysed neuroblastoma cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant cellular therapy when combined with cytotoxic chemotherapy approaches. PMID:22397715

  20. Leishmaniasis in humans: drug or vaccine therapy?

    Directory of Open Access Journals (Sweden)

    Ghorbani M

    2017-12-01

    Full Text Available Masoud Ghorbani, Ramin Farhoudi Department of Viral Vaccine Production, Pasteur Institute of Iran, Research and Production Complex, Karaj, Iran Abstract: Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome, are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results. Keywords: leishmania, leishmania treatment, vaccine, recombinant antigens

  1. Engineering HSV-1 vectors for gene therapy.

    Science.gov (United States)

    Goins, William F; Huang, Shaohua; Cohen, Justus B; Glorioso, Joseph C

    2014-01-01

    Virus vectors have been employed as gene transfer vehicles for various preclinical and clinical gene therapy applications, and with the approval of Glybera (alipogene tiparvovec) as the first gene therapy product as a standard medical treatment (Yla-Herttuala, Mol Ther 20: 1831-1832, 2013), gene therapy has reached the status of being a part of standard patient care. Replication-competent herpes simplex virus (HSV) vectors that replicate specifically in actively dividing tumor cells have been used in Phase I-III human trials in patients with glioblastoma multiforme, a fatal form of brain cancer, and in malignant melanoma. In fact, T-VEC (talimogene laherparepvec, formerly known as OncoVex GM-CSF) displayed efficacy in a recent Phase III trial when compared to standard GM-CSF treatment alone (Andtbacka et al. J Clin Oncol 31: sLBA9008, 2013) and may soon become the second FDA-approved gene therapy product used in standard patient care. In addition to the replication-competent oncolytic HSV vectors like T-VEC, replication-defective HSV vectors have been employed in Phase I-II human trials and have been explored as delivery vehicles for disorders such as pain, neuropathy, and other neurodegenerative conditions. Research during the last decade on the development of HSV vectors has resulted in the engineering of recombinant vectors that are totally replication defective, nontoxic, and capable of long-term transgene expression in neurons. This chapter describes methods for the construction of recombinant genomic HSV vectors based on the HSV-1 replication-defective vector backbones, steps in their purification, and their small-scale production for use in cell culture experiments as well as preclinical animal studies.

  2. Drug dosing during continuous renal replacement therapy.

    Science.gov (United States)

    Churchwell, Mariann D; Mueller, Bruce A

    2009-01-01

    Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT.

  3. Genetically engineering adenoviral vectors for gene therapy.

    Science.gov (United States)

    Coughlan, Lynda

    2014-01-01

    Adenoviral (Ad) vectors are commonly used for various gene therapy applications. Significant advances in the genetic engineering of Ad vectors in recent years has highlighted their potential for the treatment of metastatic disease. There are several methods to genetically modify the Ad genome to incorporate retargeting peptides which will redirect the natural tropism of the viruses, including homologous recombination in bacteria or yeast. However, homologous recombination in yeast is highly efficient and can be achieved without the need for extensive cloning strategies. In addition, the method does not rely on the presence of unique restriction sites within the Ad genome and the reagents required for this method are widely available and inexpensive. Large plasmids containing the entire adenoviral genome (~36 kbp) can be modified within Saccharomyces cerevisiae yeast and genomes easily rescued in Escherichia coli hosts for analysis or amplification. A method for two-step homologous recombination in yeast is described in this chapter.

  4. Nanostructured materials for applications in drug delivery and tissue engineering.

    Science.gov (United States)

    Goldberg, Michael; Langer, Robert; Jia, Xinqiao

    2007-01-01

    Research in the areas of drug delivery and tissue engineering has witnessed tremendous progress in recent years due to their unlimited potential to improve human health. Meanwhile, the development of nanotechnology provides opportunities to characterize, manipulate and organize matter systematically at the nanometer scale. Biomaterials with nano-scale organizations have been used as controlled release reservoirs for drug delivery and artificial matrices for tissue engineering. Drug-delivery systems can be synthesized with controlled composition, shape, size and morphology. Their surface properties can be manipulated to increase solubility, immunocompatibility and cellular uptake. The limitations of current drug delivery systems include suboptimal bioavailability, limited effective targeting and potential cytotoxicity. Promising and versatile nano-scale drug-delivery systems include nanoparticles, nanocapsules, nanotubes, nanogels and dendrimers. They can be used to deliver both small-molecule drugs and various classes of biomacromolecules, such as peptides, proteins, plasmid DNA and synthetic oligodeoxynucleotides. Whereas traditional tissue-engineering scaffolds were based on hydrolytically degradable macroporous materials, current approaches emphasize the control over cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix (ECM). The understanding that the natural ECM is a multifunctional nanocomposite motivated researchers to develop nanofibrous scaffolds through electrospinning or self-assembly. Nanocomposites containing nanocrystals have been shown to elicit active bone growth. Drug delivery and tissue engineering are closely related fields. In fact, tissue engineering can be viewed as a special case of drug delivery where the goal is to accomplish controlled delivery of mammalian cells. Controlled release of therapeutic factors in turn will enhance the efficacy of tissue engineering. From a materials

  5. Can psychedelic compounds play a part in drug dependence therapy?

    Science.gov (United States)

    Sessa, Ben; Johnson, Matthew W

    2015-01-01

    After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area. Royal College of Psychiatrists.

  6. Metabolomics has the potential to improve drug therapy

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

    2014-01-01

    Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more...

  7. [Medical quality circles for drug replacement therapy].

    Science.gov (United States)

    Tönies, Hans; Maier, Manfred; Bäwert, Andjela

    2006-08-01

    Drug replacement therapy using synthetic opioids is in Vienna mostly carried out by primary care physicians. Group teaching in quality assurance groups has been installed in order to give these doctors the necessary personal and informational assistance. Evaluation has shown that: 1. 90% of the doctors were highly or well satisfied with the teaching. Only 10% were slightly critical. 2. They could better communicate with, and were able to show more tolerance towards, the "difficult" patients. 3. Specialized knowledge increased (risk of infection, "management of hepatitis", contact with authorities, co-medication). 4. Some critical remarks pointed towards ways in which this particular further education could in future be better organized and dealt with more intensively.

  8. Management of noninfectious posterior uveitis with intravitreal drug therapy

    Directory of Open Access Journals (Sweden)

    Tan HY

    2016-10-01

    Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

  9. Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

    Science.gov (United States)

    Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

    2015-03-01

    Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

  10. New developments in atrial antiarrhythmic drug therapy

    Science.gov (United States)

    Burashnikov, Alexander; Antzelevitch, Charles

    2010-01-01

    Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Currently available antiarrhythmic drugs (AADs), although highly effective in acute cardioversion of paroxysmal AF, are generally only moderately successful in long-term maintenance of sinus rhythm. The use of AADs is often associated with an increased risk of ventricular proarrhythmia, extracardiac toxicity, and exacerbation of concomitant diseases such as heart failure. AF is commonly associated with intracardiac and extracardiac disease, which can modulate the efficacy and safety of AAD therapy. In light of the multifactorial intracardiac and extracardiac causes of AF generation, current development of anti-AF agents is focused on modulation of ion channel activity as well as on upstream therapies that reduce structural substrates. The available data indicate that multiple ion channel blockers exhibiting potent inhibition of peak INa with relatively rapid unbinding kinetics, as well as inhibition of late INa and IKr, may be preferable for the management of AF when considering both safety and efficacy. PMID:20179721

  11. Engineering Therapies that Evolve to Autonomously Control Epidemics

    Science.gov (United States)

    2017-06-01

    FINAL TECHNICAL REPORT Grant No. D15AP00024 “ Engineering Therapies that Evolve to Autonomously Control Epidemics” PI: Leor Weinberger...viruses could be engineered into therapeutics, known as Therapeutic Interfering Particles (’TIPs’), using the virus HIV as a model system. By engineering ... engineered TIPs could have indefinite, population-scale impact. To achieve this aim, we developed novel multi-scale models that connected the measured

  12. Targeted cancer therapy; nanotechnology approaches for overcoming drug resistance.

    Science.gov (United States)

    Gao, Yan; Shen, Jacson K; Milane, Lara; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-01-01

    Recent advances in cancer molecular biology have resulted in parallel and unprecedented progress in the development of targeted cancer therapy. Targeted therapy can provide higher efficacy and lower toxicity than conventional chemotherapy for cancer. However, like traditional chemotherapy, molecularly targeted cancer therapy also faces the challenge of drug resistance. Multiple mechanisms are responsible for chemotherapy resistance in tumors, including over-expression of efflux transporters, somatic alterations of drug targets, deregulation of apoptosis, and numerous pharmacokinetic issues. Nanotechnology based approaches are proving to be efficacious in overcoming drug resistance in cancer. Combination of targeted therapies with nanotechnology approaches is a promising strategy to overcome targeted therapy drug resistance in cancer treatment. This review discusses the mechanisms of targeted drug resistance in cancer and discusses nanotechnology approaches to circumvent this resistance.

  13. Re: Engineered Nanoparticles Induce Cell Apoptosis: Potential for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-09-01

    Full Text Available Engineered nanoparticles (ENPs have been widely applied in industry, biology and medicine recently (i.e. clothes, sunscreens, cosmetics, foods, diagnostic medicine, imaging and drug delivery. There are many kinds of manufactured nanomaterial products including TiO2, ZnO, CeO2, Fe2O3, and CuO (as metal oxide nanoparticles as well as gold, silver, platinum and palladium (as metal nanoparticles, and other carbon-based ENP’s such as carbon nanotububes and quantum dots. ENPs with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs and cause toxic effects. In many researches, ENP effects on the cancer cells of different organs with related cell apoptosis were noted (AgNP, nano-Cr2O3, Au-Fe2O3 NPs, nano-TiO2, nano-HAP, nano-Se, MoO3 nanoplate, Realgar nanoparticles. ENPs, with their unique properties, such as surface charge, particle size, composition and surface modification with tissue recognition ligands or antibodies, has been increasingly explored as a tool to carry small molecular weight drugs as well as macromolecules for cancer therapy, thus generating the new concept “nanocarrier”. Direct induction of cell apoptosis by ENPs provides an opportunity for cancer treatment. In the century of nanomedicine that depends on development of the nanotechnology, ENPs have a great potential for application in cancer treatment with minimal side effects.

  14. Approaches and Challenges of Engineering Implantable Microelectromechanical Systems (MEMS Drug Delivery Systems for in Vitro and in Vivo Applications

    Directory of Open Access Journals (Sweden)

    Ken-Tye Yong

    2012-11-01

    Full Text Available Despite the advancements made in drug delivery systems over the years, many challenges remain in drug delivery systems for treating chronic diseases at the personalized medicine level. The current urgent need is to develop novel strategies for targeted therapy of chronic diseases. Due to their unique properties, microelectromechanical systems (MEMS technology has been recently engineered as implantable drug delivery systems for disease therapy. This review examines the challenges faced in implementing implantable MEMS drug delivery systems in vivo and the solutions available to overcome these challenges.

  15. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Tissue Engineering in Regenerative Dental Therapy

    Directory of Open Access Journals (Sweden)

    Hiral Jhaveri-Desai

    2011-01-01

    Full Text Available Tissue engineering is amongst the latest exciting technologies having impacted the field of dentistry. Initially considered as a futuristic approach, tissue engineering is now being successfully applied in regenerative surgery. This article reviews the important determinants of tissue engineering and how they contribute to the improvement of wound healing and surgical outcomes in the oral region. Furthermore, we shall address the clinical applications of engineering involving oral and maxillofacial surgical and periodontal procedures along with other concepts that are still in experimental phase of development. This knowledge will aid the surgical and engineering researchers to comprehend the collaboration between these fields leading to extounding dental applications and to ever-continuing man-made miracles in the field of human science.

  17. Engineering bioceramic microstructure for customized drug delivery

    Science.gov (United States)

    Pacheco Gomez, Hernando Jose

    One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (pSCPC (pSCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was found to correlate with the pore size distribution and surface area. Furthermore, the average rates of sustained release in the period 8-216h from Cris, Rhe and SCPC were: 9.8, 7.2 and 3.5 mug/h of Vanc and 4.5, 5.3 and 3.5 mug/h of Cis, respectively. Nearly inert Cris ceramic showed release kinetics controlled by its hierarchical nano porous structure. On the other hand, the phase composition

  18. Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

    Science.gov (United States)

    de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

    2015-01-01

    Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

  19. Engineered Liver Platforms for Different Phases of Drug Development.

    Science.gov (United States)

    Ware, Brenton R; Khetani, Salman R

    2017-02-01

    Drug-induced liver injury (DILI) remains a leading cause of drug withdrawal from human clinical trials or the marketplace. Owing to species-specific differences in liver pathways, predicting human-relevant DILI using in vitro human liver models is crucial. Microfabrication tools allow precise control over the cellular microenvironment towards stabilizing liver functions for weeks. These tools are used to engineer human liver models with different complexities and throughput using cell lines, primary cells, and stem cell-derived hepatocytes. Including multiple human liver cell types can mimic cell-cell interactions in specific types of DILI. Finally, organ-on-a-chip models demonstrate how drug metabolism in the liver affects multi-organ toxicities. In this review we survey engineered human liver platforms within the needs of different phases of drug development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Predicting Drug Recalls From Internet Search Engine Queries.

    Science.gov (United States)

    Yom-Tov, Elad

    2017-01-01

    Batches of pharmaceuticals are sometimes recalled from the market when a safety issue or a defect is detected in specific production runs of a drug. Such problems are usually detected when patients or healthcare providers report abnormalities to medical authorities. Here, we test the hypothesis that defective production lots can be detected earlier by monitoring queries to Internet search engines. We extracted queries from the USA to the Bing search engine, which mentioned one of the 5195 pharmaceutical drugs during 2015 and all recall notifications issued by the Food and Drug Administration (FDA) during that year. By using attributes that quantify the change in query volume at the state level, we attempted to predict if a recall of a specific drug will be ordered by FDA in a time horizon ranging from 1 to 40 days in future. Our results show that future drug recalls can indeed be identified with an AUC of 0.791 and a lift at 5% of approximately 6 when predicting a recall occurring one day ahead. This performance degrades as prediction is made for longer periods ahead. The most indicative attributes for prediction are sudden spikes in query volume about a specific medicine in each state. Recalls of prescription drugs and those estimated to be of medium-risk are more likely to be identified using search query data. These findings suggest that aggregated Internet search engine data can be used to facilitate in early warning of faulty batches of medicines.

  1. Nanomaterial-based drug delivery carriers for cancer therapy

    CERN Document Server

    Feng, Tao

    2017-01-01

    This brief summarizes different types of organic and inorganic nanomaterials for drug delivery in cancer therapy. It highlights that precisely designed nanomaterials will be the next-generation therapeutic agents for cancer treatment.

  2. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

    Science.gov (United States)

    Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

    2016-01-01

    Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

  3. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  4. Drug Therapy Problems in Patients on Antihypertensives and ...

    African Journals Online (AJOL)

    Drug therapy problems (DTPs), with the associated risks inherent in antihypertensive and antidiabetic therapy require utmost attention. This present study was aimed at assessing the DTPs observed in the management of hypertension and diabetes mellitus (DM) in two tertiary health facilities in Niger Delta region. In this ...

  5. Methadone maintenance therapy as evidence based drug abuse ...

    African Journals Online (AJOL)

    Methadone maintenance therapy as evidence based drug abuse planning in developed countries: Can developing countries afford and learn from this experience? ... However, various studies and preventive approaches have been tried in the US on drug abusers in order to prevent the associated adverse health outcomes.

  6. Gene engineering biological therapy for juvenile arthritis

    Directory of Open Access Journals (Sweden)

    Kh Mikhel's

    2011-01-01

    However, GEBA therapy cannot completely cure the disease as before despite the progress achieved. GEBAs have potentially a number of serious side effects, among which there are severe infections and there is a risk of developing malignancies and autoimmune processes. Their administration requires careful monitoring to reveal the early development of serious adverse reactions, thus preventing a poor outcome.

  7. Review paper: critical issues in tissue engineering: biomaterials, cell sources, angiogenesis, and drug delivery systems.

    Science.gov (United States)

    Naderi, Hojjat; Matin, Maryam M; Bahrami, Ahmad Reza

    2011-11-01

    Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

  8. Behaviour therapy for obesity treatment considering approved drug therapy

    OpenAIRE

    Wasem, Jürgen; Ulle, Tanja; Kahl, Kai G; Kossmann, Beate; Aidelsburger, Pamela

    2008-01-01

    Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Und...

  9. Drug dosing during continuous renal replacement therapies

    National Research Council Canada - National Science Library

    Thompson, A Jill

    2008-01-01

    ... in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal function...

  10. Nanofibers: New Insights for Drug Delivery and Tissue Engineering.

    Science.gov (United States)

    Haidar, Mohammad Karim; Eroglu, Hakan

    2017-01-01

    Nanofibers became one of the major research areas for drug delivery and tissue engineering applications in the last decade. Depending on the simplicity of the preparation method and high drug loading capacity, nanofibers provide many advantages for therapeutic perspectives. In addition, combined systems such as embedding nanoparticles into the nanofiber structures provide a second option for delivery of dual active ingredients in the same formulation. The release rate of the active ingredients can also be modified easily by the formulation parameters depending on the desired release time for treatment. Nanofibers systems are used for the delivery of antibiotics, anticancer drugs, analgesics, hemostatic agents and various proteins for tissue engineering purposes. In addition, various applications such as medical device coating also provide new insights for the clinical use of nanofibers. The most commonly used technique for preparation of nanofibers is the electrospinning, which provides feasibility background for scale up process from laboratory to the industrial applications. The main boundary for nanofibers is the limitations for systemic route. Nanofibers are mainly designed for the delivery of active ingredients for local purposes. Regardless of the therapeutic aim, nanofibers are also perfect 3 dimensional structures that are suitable for tissue regeneration. They provide matrix structure for cell regeneration especially in applications for wound healing. This review is mainly focused on the recent advances on the preparation of nanofibers, applications for drug delivery, tissue engineering and wound healing purposes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. [The microencapsulated genetic engineering cells: a new platform on treatment of cancer instead of genetic engineering drugs].

    Science.gov (United States)

    Pan, Yuelong; Zheng, Shu

    2003-06-01

    The microencapsulated genetic cells may be a new platform instead of genetic engineering drugs, as they can overcome the genetic engineering drugs' shortages such as short half-life in vivo, low activity, and incomplete elimination of organic solvent. This article reviews and summarizes the advantages, possible problems and solution and the feasibility of using microencapsulated genetic engineering cells in the treatment of cancer.

  12. Drug loaded magnetic nanoparticles for cancer therapy

    Science.gov (United States)

    Jurgons, R.; Seliger, C.; Hilpert, A.; Trahms, L.; Odenbach, S.; Alexiou, C.

    2006-09-01

    Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. In medicine they are used for several approaches such as magnetic cell separation or magnetic resonance imaging (MRI). The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is the focus of medical research, especially for the treatment of cancer and diseases of the vascular system. In an experimental cancer model, we performed targeted drug delivery and used magnetic iron oxide nanoparticles, bound to a chemotherapeutic agent, which were attracted to an experimental tumour in rabbits by an external magnetic field (magnetic drug targeting). Complete tumour remission could be achieved. An important advantage of these carriers is the possibility for detecting these nanoparticles after treatment with common imaging techniques (i.e. x-ray-tomography, magnetorelaxometry, magnetic resonance imaging), which can be correlated to histology.

  13. Micro- and Nanoscale Hydrogel Systems for Drug Delivery and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Ipsita A. Banerjee

    2009-05-01

    Full Text Available The pursuit for targeted drug delivery systems has led to the development of highly improved biomaterials with enhanced biocompatibility and biodegradability properties. Micro- and nanoscale components of hydrogels prepared from both natural and artificial components have been gaining significant importance due to their potential uses in cell based therapies, tissue engineering, liquid micro-lenses, cancer therapy, and drug delivery. In this review some of the recent methodologies used in the preparation of a number of synthetic hydrogels such as poly(N-isopropylacrylamide (pNIPAm, poly(ethylene glycol (PEG, poly(ethylene oxide (PEO, polyvinyl alcohol methylacrylate co-polymers (PVA-MA and polylactic acid (PLA, as well as some of the natural hydrogels and their applications have been discussed in detail.

  14. Drug therapy during pregnancy: implications for dental practice.

    Science.gov (United States)

    Ouanounou, A; Haas, D A

    2016-04-22

    Pregnancy is accompanied by various physiological and physical changes, including those found in the cardiovascular, respiratory, gastrointestinal, renal and haematological systems. These alterations in the pregnant patient may potentially affect drug pharmacokinetics. Also, pharmacotherapy presents a unique matter due to the potential teratogenic effects of certain drugs. Although medications prescribed by dentists are generally safe during pregnancy, some modifications may be needed. In this article we will discuss the changes in the physiology during pregnancy and its impact on drug therapy. Specific emphasis will be given to the drugs commonly given by dentists, namely, local anaesthetics, analgesics, antibiotics and sedatives.

  15. [Drug therapy and hypertension in the newspapers].

    Science.gov (United States)

    Collin, Johanne; Hughes, David

    2010-01-01

    The most recent country-wide Canadian data have revealed that only 33% of people with hypertension take medication and fewer than half of them have their blood pressure under control. One of the most important reasons for difficulty in controlling blood pressure is lack of drug treatment compliance. In addition, media coverage of health facts has an impact on beliefs, attitudes and behaviours related to health. Our goal was to analyze newspaper coverage of drugs related to hypertension. We conducted a thematic content analysis of newspapers covering medications related to hypertension. The study comprised 104 articles drawn from three of the most important francophone daily newspapers in Canada--a reference one, a general broadsheet and a tabloid. We identified three major themes: 1) drugs as an effective treatment, 2) specific problematic cases, and 3) problems with the pharmacological approach in general. We noted a gradual change from positive to negative as we moved from the most serious newspaper to the most popular. We discuss the Fiske hypothesis which suggests that tabloid-format newspapers are a repository of popular opposition to the discourse of groups who hold power in society. In the tabloid, the most widely-read newspaper in Quebec, medications are often presented in negative fashion in articles on hypertension. However, further studies are required to determine if there is a causal association between media discourse and the phenomenon of lack of drug treatment compliance.

  16. Monitoring drug therapy in hospitalized patients

    NARCIS (Netherlands)

    Uijtendaal, E.V.

    2014-01-01

    Prevention of adverse drug events that may result from medication errors is challenging. The safety of medication treatment is mostly determined on an average population and medication errors may be prevented when pharmacotherapy is better tailored to the individualized needs of the hospitalized

  17. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

  18. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study.

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients' engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants ( n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed.

  19. Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

    Directory of Open Access Journals (Sweden)

    Mario Degli Stefani

    2016-10-01

    Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

  20. [Non-drug therapies, working on emotions].

    Science.gov (United States)

    Detournay-Hentgen, Marie-Carmel

    2015-11-01

    Cognitive behavioural therapies are indicated for people in mental pain and also recommended in the treatment of a variety of psychological disorders. The aim is to replace the inappropriate behaviour by more adapted behaviour. Positive psychology is interested not so much in mental health disorders as in well-being and happiness. A variety of therapeutic trends which the caregiver can use to help and support patients in regaining their bearings. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Spiritual self-schema therapy, drug abuse, and HIV.

    Science.gov (United States)

    Marcotte, David; Avants, S Kelly; Margolin, Arthur

    2003-01-01

    This case report describes the use of Spiritual Self-Schema (3-S) therapy in the treatment of an HIV-positive inner-city drug user maintained on methadone and referred for additional treatment due to unremitting cocaine use. 3-S therapy is a manual-guided intervention based on cognitive self-schema theory. Its goal is to help the patient create, elaborate, and make accessible a cognitive schema--the "spiritual" self-schema-that is incompatible with drug use and other HIV risk behaviors. 3-S therapy facilitates a cognitive shift from the habitual activation of the "addict" self-schema, with its drug-related cognitions, scripts and action plans, to the "spiritual" self-schema, with its associated repertoire of harm reduction beliefs and behaviors.

  2. Nanotechnology approaches for pain therapy through transdermal drug delivery.

    Science.gov (United States)

    Peptu, Cristian; Rotaru, Razvan; Ignat, Leonard; Humelnicu, Andra Cristina; Harabagiu, Valeria; Peptu, Catalina Anisoara; Leon, Maria-Magdalena; Mitu, Florin; Cojocaru, Elena; Boca, Andreea; Tamba, Bogdan Ionel

    2015-01-01

    The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.

  3. REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

    OpenAIRE

    BROSCATEAN, Emanuela-Flavia; DOGARU Gabriela

    2013-01-01

    Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone....

  4. Nanotechnology inspired advanced engineering fundamentals for optimizing drug delivery.

    Science.gov (United States)

    Kassem, Ahmed Alaa

    2018-02-06

    Drug toxicity and inefficacy are commonly experienced problems with drug therapy failure. To face these problems, extensive research work took place aiming to design new dosage forms for drug delivery especially nanoparticulate systems. These systems are designed to increase the quantity of the therapeutic molecule delivered to the desired site concurrently with reduced side effects. In order to achieve this objective, nanocarriers must principally display suitable drug vehiculization abilities and a controlled biological destiny of drug molecules. Only the intelligent design of the nanomedicine will accomplish these fundamentals. The present review article is dedicated to the discussion of the important fundamentals to be considered in the fabrication of nanomedicines. These include the therapeutic agent, the nanocarrier and the functionalization moieties. Special consideration is devoted to the explanation and compilation of highly potential fabrication approaches assisting how to control the in vivo destiny of the nanomedicine. Finally, some nanotechnology-based drug delivery systems, for the development of nanomedicine, are also discussed. The nanotechnology-based drug delivery systems showed remarkable outcomes based on passive and active targeting as well as improvement of the drug pharmacodynamic and pharmacokinetic profiles. Multifunctional nanocarrier concept affords a revolutionary drug delivery approach for maximizing the efficacy, safety and monitoring the biological fate of the therapeutic molecule. Nanomedicines may enhance the efficacy of therapeutic molecules and reduce their toxic effects. Meanwhile, further research works are required to rightly optimize (and define) the effectiveness, nanotoxicity, in vivo destiny and feasibility of these nanomedicines which, from a preclinical standpoint, are actually promising. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Engineering liposomal nanoparticles for targeted gene therapy.

    Science.gov (United States)

    Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

    2017-08-01

    Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

  6. Drug Therapy in Adult Congenital Heart Disease.

    Science.gov (United States)

    Contractor, Tahmeed; Levin, Vadim; Mandapati, Ravi

    2017-06-01

    Adults with congenital heart disease are at risk for atrial and ventricular arrhythmias that can lead to an increased morbidity as well as mortality. When catheter ablation is not an option or unsuccessful, antiarrhythmic drugs are the mainstay of treatment. There is limited data on the use of antiarrhythmics in this population. The purpose of this article is to discuss the practical aspects of the use of antiarrhythmics in adults with congenital heart disease. Several tables have been provided to provide clinicians a reference for daily use. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Drug Carrier for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Tilahun Ayane Debele

    2015-09-01

    Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

  8. [Drug therapy for older people : Choosing wisely].

    Science.gov (United States)

    Wehling, Martin

    2017-09-22

    Elderly people are the most rapidly growing sector of our society. Due to their multimorbidity they are exposed to a multitude of medications, which are accompanied by chances and risks. The problem of inappropriate medication in the elderly is exacerbated by the fact that only a holistic view can help these patients and that this is predominantly the responsibility of the general practitioner. The closely measured paid contact time is often insufficient to optimize complex medications. Clinically successfully tested aids in the form of lists give reason for hope: in particular, the positive/negative assessment of limitations of the elderly with respect to drugs by the STOPP/START criteria and the FORTA classification are clinically successful aids. Purely negative lists, such as the Beers or PRISCUS lists, have been disappointing in clinical application because they do not consider the needs, prognostic and particularly symptomatic importance and weighting of the diagnosis of patients. Further implementation of these aids to decision making should help to improve the problem of care of elderly patients in the field of drug treatment, even in IT systems.

  9. The Functions and Applications of RGD in Tumor Therapy and Tissue Engineering

    Science.gov (United States)

    Wang, Fen; Li, Yuanyuan; Shen, Yingqiang; Wang, Anming; Wang, Shuling; Xie, Tian

    2013-01-01

    Arginine-Glycine-Aspartic (RGD), is the specific recognition site of integrins with theirs ligands, and regulates cell-cell and cell-extracellular matrix interactions. The RGD motif can be combined with integrins overexpressed on the tumor neovasculature and tumor cells with a certain affinity, becoming the new target for imaging agents, and drugs, and gene delivery for tumor treatment. Further, RGD as a biomimetic peptide can also promote cell adherence to the matrix, prevent cell apoptosis and accelerate new tissue regeneration. Functionalizing material surfaces with RGD can improve cell/biomaterial interactions, which facilitates the generation of tissue-engineered constructs. This paper reviews the main functions and advantages of RGD, describes the applications of RGD in imaging agents, drugs, gene delivery for tumor therapy, and highlights the role of RGD in promoting the development of tissue engineering (bone regeneration, cornea repair, artificial neovascularization) in recent years. PMID:23807504

  10. [Dyslipidemia: news in diagnosis and drug therapy].

    Science.gov (United States)

    Cattin, Luigi; Spangano, Franco; Fonda, Maurizio

    2012-01-01

    Plasma lipid levels are to a large extent determined by genetic factors. In its more extreme forms this is manifested as familial hyperlipidemias, which are an important cause of premature coronary heart disease. It has been demonstrated that rigorous treatment of familial forms reduces the burden of ischemic heart disease. Statins are among the most studied drugs in cardiovascular prevention; a number of large-scale clinical trials have demonstrated that statins substantially reduce cardiovascular morbidity and mortality in both primary and secondary prevention. The currently available evidence suggests that the clinical benefit is largely independent of the type of statin, but depends on the extent of LDL-C lowering. When the most potent statins are insufficient, LDL-C apheresis should be used.

  11. Genetically engineered multivalent single chain antibody constructs for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Surinder Batra, Ph D

    2006-02-27

    Current therapeutic approaches against the advanced stages of human solid tumors are palliative rather than curative. Many modalities, including, surgery, radiation, and chemotherapy, either alone or in combination have met with only modest success for advanced metastatic cancers. Radioimmunotherapy (RIT) combines the specificity of monoclonal antibodies with cytotxic effects of radioisotopes. It is the smart way of delivering radiation to the known and occult metastatic cancer cells and is independent of drug toxicity and/or hormone resistance. The tumor associated glycoprotein-72 (TAG-72) containing the unique disaccharide sialyl-Tn, is highly expressed in majority of adenocarcinomas, including carcinomas of the prostate, breast, ovaries, pancreas and colon (80-90%) compared to undetectable expression in normal tissues. Monoclonal antibody CC49, reactive with TAG-72, after conjugation to potent gamma- and beta-emitting radionuclides, has been useful in selective systemic radiolocalization of disease and therapy of primary and metastatic tumor sites. However, limited therapeutic responses were observed in patients. Limited success of antibody based delivery of radioisotopes can be attributed to several factors including undesirable pharmacokinetics, poor tumor uptake and high immunogenicity of intact antibodies (IgGs). The primary factors contributing towards the failure of RIT include: 1) longer serum half-lives of the intact IgG molecules resulting in the radiotoxicity, 2) generation of human antibodies against murine antibodies (HAMA) that limits the frequency of dose administration, 3) poor diffusion rates of intact IgG due to the large size and 4) high interstitial fluid pressures (IFP) encountered in solid tumors. The major goal of our multidisciplinary project was to develop specific novel radiopharmaceuticals, with desired pharmacokinetics, for the diagnosis and therapy of solid tumors. To overcome the low uptake of radioactivity by tumors and to increase

  12. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  13. Chimeric antigen receptor engineered stem cells: a novel HIV therapy.

    Science.gov (United States)

    Zhen, Anjie; Carrillo, Mayra A; Kitchen, Scott G

    2017-03-01

    Despite the success of combination antiretroviral therapy (cART) for suppressing HIV and improving patients' quality of life, HIV persists in cART-treated patients and remains an incurable disease. Financial burdens and health consequences of lifelong cART treatment call for novel HIV therapies that result in a permanent cure. Cellular immunity is central in controlling HIV replication. However, HIV adopts numerous strategies to evade immune surveillance. Engineered immunity via genetic manipulation could offer a functional cure by generating cells that have enhanced antiviral activity and are resistant to HIV infection. Recently, encouraging reports from several human clinical trials using an anti-CD19 chimeric antigen receptor (CAR) modified T-cell therapy for treating B-cell malignancies have provided valuable insights and generated remarkable enthusiasm in engineered T-cell therapy. In this review, we discuss the development of HIV-specific chimeric antigen receptors and the use of stem cell based therapies to generate lifelong anti-HIV immunity.

  14. Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse:

    DEFF Research Database (Denmark)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2015-01-01

    trials. Meta-analytic methods were used to quantitatively synthesize study results.  Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long...... run and demonstrated positive effects on treatment retention compared to control conditions.  Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however......Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use.  Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized...

  15. Evaluation of drug therapy problems among renal patients receiving ...

    African Journals Online (AJOL)

    Purpose: To determine the prevalence of drug therapy problems (DTPs), identify the types of DTPs and assess outcomes of DTP interventions among renal patients receiving care in three Nigerian tertiary hospitals. Methods: This prospective descriptive study was conducted in nephrology units of three tertiary hospitals in ...

  16. Assessment of patients' knowledge of their drug therapy in a ...

    African Journals Online (AJOL)

    Patients' knowledge of their medications is an important factor in ensuring adherence. Medication adherence is essential for rational drug use and derivation of optimal therapy. This study was conducted to assess knowledge of outpatients regarding their medications. A well structured questionnaire was administered to 200 ...

  17. Multimodal ultrasound mediated drug release model in local cancer therapy.

    Science.gov (United States)

    Myhr, Gunnar

    2007-01-01

    Increased cancer survival rates over the last decades are probably less due to advances of a single treatment modality than to optimization of adjuvant treatment procedures. The efficiency of drug delivery in solid tumours is crucial for achieving local tumour control as cytotoxic agents do not target cancer cells selectively. To enhance tumour uptake and selectivity of drugs, liposomally encapsulated microbubbles with drugs or temperature sensitive liposomes with therapeutics have been suggested as new drug delivery vehicles, in combination with ultrasound or hyperthermia, respectively. The presented release model goes beyond simple drug delivery or traditional adjuvant therapies. It represents targeting, real time monitoring and imaging, and exerts concurrent application of therapeutic modalities, within a multimodal treatment regime, thus enhancing synergism. An appropriate diagnostic tool is applied to determine the region of interest with respect to reference coordinates. The delineated region of interest can be modelled by topographic modelling techniques. A subsequent adequate digital tumour model can facilitate an optimal treatment procedure. The system integrates a diagnostic unit with a therapeutic ultrasonic transmitting component, together with a central processing unit, encompassing algorithms for data processing and visualization. Actual drug uptake is based on passive accumulation of drug carriers. Selective drug release of e.g. cytostatic drugs is achieved by ultrasound induced cavitation well defined to the tumour region. Monitoring of drug release can be achieved by imaging techniques. Measurement and monitoring of cavitational activities within the volume of release, and established functional relationships between cavitation level and drug release, will be bridged to various control functions by the processing unit. Further concurrent thermal treatment approaches and ionizing radiation modi are proposed within the comprehensive treatment model

  18. Drug therapy in patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Müller Thomas

    2012-05-01

    Full Text Available Abstract Parkinson`s disease (PD is a progressive, disabling neurodegenerative disorder with onset of motor and non-motor features. Both reduce quality of life of PD patients and cause caregiver burden. This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other. MAO-B-Inhibitors, NMDA antagonists, dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD. This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms. These PD features predominantly result from non dopaminergic neurodegeneration. Autonomic features, such as seborrhea, hyperhidrosis, orthostatic syndrome, salivation, bladder dysfunction, gastrointestinal disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis, cognitive dysfunction with impaired execution and impulse control may appear. Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions, - side effects, and altered pharmacokinetic behaviour of applied compounds. Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms. This complicates the differentiation from the disease process itself and influences therapeutic options, which are often limited because of additional morbidity with necessary concomitant drug therapy.

  19. Multifunctional magnetic nanostructured hardystonite scaffold for hyperthermia, drug delivery and tissue engineering applications.

    Science.gov (United States)

    Farzin, Ali; Fathi, Mohammadhossein; Emadi, Rahmatollah

    2017-01-01

    Hyperthermia and local drug delivery have been proposed as potential therapeutic approaches for killing cancer cells. The development of bioactive materials such as Hardystonite (HT) with magnetic and drug delivery properties can potentially meet this target. This new class of magnetic bioceramic can replace the widely used magnetic iron oxide nanoparticles, whose long-term biocompatibility is not clear. Magnetic HT can be potentially employed to develop new ceramic scaffolds for bone surgery and anticancer therapies. With this in mind, a synthesis procedure was developed to prepare multifunctional bioactive scaffold for tissue engineering, hyperthermia and drug delivery applications. To this end, iron (Fe(3+))-containing HT scaffolds were prepared. The effect of Fe on biological, magnetic and drug delivery properties of HT scaffolds were investigated. The results showed that obtained Fe-HT is bioactive and magnetic with no magnetite or maghemite as secondary phases. The Fe-HT scaffolds obtained also possessed high specific surface areas and demonstrated sustained drug delivery. These results potentially open new aspects for biomaterials aimed at regeneration of large-bone defects caused by malignant bone tumors through a combination of hyperthermia, local drug delivery and osteoconductivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Wunderlich syndrome during antiplatelet drug therapy.

    Science.gov (United States)

    Capitanini, A; Tavolaro, A; Rosellini, M; Rossi, A

    2009-03-01

    Spontaneous hemorrhage in the kidney, also known as Wunderlich Syndrome, is a rare clinical problem. The most common cause of spontaneous renal hemorrhage is tumor. Other causes are rupture of a renal cyst, vasculitis, hydronephrosis, preeclampsia, and kidney infections. A 67-year-old man was admitted complaining left flank colic pain. A contrast CT scan showed the presence of a subcapsular hematoma of the left kidney extending from the upper to the lower pole. He had no history of trauma and immunological screening tests for vasculitis were normal. His current therapy included acetylsalicylic acid (100 mg/daily) and lisinopril (20 mg/ daily). The patient was hospitalized for 4 days and his circulatory state remained stable. Nine months later an ultrasound examination showed complete resolution of the hematoma. One year later the patient was admitted again because of a spontaneous right calf hematoma and a thoroughly investigation of his coagulation pattern was carried out. Laboratory finding revealed a platelet defect, as the number of adenine nucleotides and other marker related to platelet activation were increased: ADP 1 mcM lack 2 masculine wave, ADP 2 mcM lack 2 masculine wave, Adrenalina 5 mcM lack 2 masculine wave, Adrenalina 10 mcM lack 2 masculine wave. Platelet activation markers: Gp53 in lysosomal membrane 0.48 Dpar (0 - 0.26). Our case describes the recurrence of spontaneous hemorrhages (perirenal and intramuscular hematoma) as a result of an underlying platelet aggregation defect worsened by administration of acetylsalicylic acid. In patients on antiplatelet treatment with a history of excessive bleeding a thorough investigation of coagulation status appears beneficial.

  1. Cardiac tissue engineering and regeneration using cell-based therapy

    Directory of Open Access Journals (Sweden)

    Alrefai MT

    2015-05-01

    Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

  2. Antimalarial drug therapy: the role of parasite biology and drug resistance.

    Science.gov (United States)

    Daily, Johanna P

    2006-12-01

    Malaria continues to affect public health and economic growth in many regions of the world. The number of infections continues to rise and is associated with increased mortality, despite basic science and public health efforts. Drug therapy remains the mainstay of treatment and prevention of this disease. Plasmodium has a complex life cycle involving an arthropod vector and distinct stages within the human host. Each parasite stage plays a unique role in transmission, disease, and latency. These different stages may vary in their response to the various antimalarial compounds. This article will review antimalarial therapies and drug resistance in the context of the parasites' biology.

  3. DNA Nanotechnology for Precise Control over Drug Delivery and Gene Therapy.

    Science.gov (United States)

    Angell, Chava; Xie, Sibai; Zhang, Liangfang; Chen, Yi

    2016-03-02

    Nanomedicine has been growing exponentially due to its enhanced drug targeting and reduced drug toxicity. It uses the interactions where nanotechnological components and biological systems communicate with each other to facilitate the delivery performance. At this scale, the physiochemical properties of delivery systems strongly affect their capacities. Among current delivery systems, DNA nanotechnology shows many advantages because of its unprecedented engineering abilities. Through molecular recognition, DNA nanotechnology can be used to construct a variety of nanostructures with precisely controllable size, shape, and surface chemistry, which can be appreciated in the delivery process. In this review, different approaches that are currently used for the construction of DNA nanostructures are reported. Further, the utilization of these DNA nanostructures with the well-defined parameters for the precise control in drug delivery and gene therapy is discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. ADHD and drug therapy: is it still a valid treatment?

    Science.gov (United States)

    Doggett, A Mark

    2004-03-01

    The purpose of this article is to discuss alternative treatments other than drug therapy for Attention-Deficit/Hyperactive Disorder (ADHD) in educational settings. There is an increasing body of knowledge that supports interventions for improving cognitive outcomes without the use of medication. The article explores the risks to ADHD children, shows the potential linkage between gifted children and ADHD, explores recent brain research, and examines various alternative treatment options. Information is presented on alternative treatments such as cognitive behavioral therapies, educational interventions, electroencephalograph (EEG) neuro-feedback, and diet.

  5. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

    Science.gov (United States)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  6. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

    Directory of Open Access Journals (Sweden)

    Jan eStenvang

    2013-12-01

    Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

  7. Repurposing FDA-approved drugs for anti-aging therapies.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Srinivasan, Bharath; Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey

    2016-11-01

    There is great interest in drugs that are capable of modulating multiple aging pathways, thereby delaying the onset and progression of aging. Effective strategies for drug development include the repurposing of existing drugs already approved by the FDA for human therapy. FDA approved drugs have known mechanisms of action and have been thoroughly screened for safety. Although there has been extensive scientific activity in repurposing drugs for disease therapy, there has been little testing of these drugs for their effects on aging. The pool of FDA approved drugs therefore represents a large reservoir of drug candidates with substantial potential for anti-aging therapy. In this paper we employ FINDSITE(comb), a powerful ligand homology modeling program, to identify binding partners for proteins produced by temperature sensing genes that have been implicated in aging. This list of drugs with potential to modulate aging rates was then tested experimentally for lifespan and healthspan extension using a small invertebrate model. Three protein targets of the rotifer Brachionus manjavacas corresponding to products of the transient receptor potential gene 7, ribosomal protein S6 polypeptide 2 gene, or forkhead box C gene, were screened against a compound library consisting of DrugBank drugs including 1347 FDA approved, non-nutraceutical molecules. Twenty nine drugs ranked in the top 1 % for binding to each target were subsequently included in our experimental analysis. Continuous exposure of rotifers to 1 µM naproxen significantly extended rotifer mean lifespan by 14 %. We used three endpoints to estimate rotifer health: swimming speed (mobility proxy), reproduction (overall vitality), and mitochondria activity (cellular senescence proxy). The natural decline in swimming speed with aging was more gradual when rotifers were exposed to three drugs, so that on day 6, mean swimming speed of females was 1.19 mm/s for naproxen (P = 0.038), 1.20 for fludarabine (P = 0

  8. Engineered CRISPR Systems for Next Generation Gene Therapies.

    Science.gov (United States)

    Pineda, Michael; Moghadam, Farzaneh; Ebrahimkhani, Mo R; Kiani, Samira

    2017-09-15

    An ideal in vivo gene therapy platform provides safe, reprogrammable, and precise strategies which modulate cell and tissue gene regulatory networks with a high temporal and spatial resolution. Clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial adoptive immune system, and its CRISPR-associated protein 9 (Cas9), have gained attention for the ability to target and modify DNA sequences on demand with unprecedented flexibility and precision. The precision and programmability of Cas9 is derived from its complexation with a guide-RNA (gRNA) that is complementary to a desired genomic sequence. CRISPR systems open-up widespread applications including genetic disease modeling, functional screens, and synthetic gene regulation. The plausibility of in vivo genetic engineering using CRISPR has garnered significant traction as a next generation in vivo therapeutic. However, there are hurdles that need to be addressed before CRISPR-based strategies are fully implemented. Some key issues center on the controllability of the CRISPR platform, including minimizing genomic-off target effects and maximizing in vivo gene editing efficiency, in vivo cellular delivery, and spatial-temporal regulation. The modifiable components of CRISPR systems: Cas9 protein, gRNA, delivery platform, and the form of CRISPR system delivered (DNA, RNA, or ribonucleoprotein) have recently been engineered independently to design a better genome engineering toolbox. This review focuses on evaluating CRISPR potential as a next generation in vivo gene therapy platform and discusses bioengineering advancements that can address challenges associated with clinical translation of this emerging technology.

  9. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  10. Stem cells engineering for cell-based therapy.

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  11. Drug therapy for the prevention and treatment of bronchopulmonary dysplasia

    Science.gov (United States)

    Iyengar, Anjali; Davis, Jonathan M.

    2015-01-01

    Introduction: As more infants are surviving at younger gestational ages, bronchopulmonary dysplasia (BPD) remains as a frequent neonatal complication occurring after preterm birth. The multifactorial nature of the disease process makes BPD a challenging condition to treat. While multiple pharmacologic therapies have been investigated over the past two decades, there have been limited advances in the field. Often multiple therapies are used concurrently without clear evidence of efficacy, with potential for significant side effects from drug-drug interactions. Methods: Systematic literature review. Conclusion: Although there is physiologic rationale for the use of many of these therapies, none of them has single-handedly altered the incidence, severity, or progression of BPD. Future research should focus on developing clinically significant end-points (short and long term respiratory assessments), investigating biomarkers that accurately predict risk and progression of disease, and creating appropriate stratification models of BPD severity. Applying a multi-modal approach to the study of new and existing drugs should be the most effective way of establishing the optimal prevention and treatment regimens for BPD. PMID:25762933

  12. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Science.gov (United States)

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

  13. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Warangkana Lohcharoenkal

    2014-01-01

    Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  14. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    Directory of Open Access Journals (Sweden)

    Toril Andersen

    2015-01-01

    Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

  15. Engineering adeno-associated viruses for clinical gene therapy.

    Science.gov (United States)

    Kotterman, Melissa A; Schaffer, David V

    2014-07-01

    Clinical gene therapy has been increasingly successful owing both to an enhanced molecular understanding of human disease and to progressively improving gene delivery technologies. Among these technologies, delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective and, in one recent case, have led to regulatory approval. Although shortcomings in viral vector properties will render extension of such successes to many other human diseases challenging, new approaches to engineer and improve AAV vectors and their genetic cargo are increasingly helping to overcome these barriers.

  16. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    Directory of Open Access Journals (Sweden)

    Michael Guarnieri

    2014-01-01

    Full Text Available Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs.

  17. Potential drug interactions in patients given antiretroviral therapy.

    Science.gov (United States)

    Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

    2016-11-21

    to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral. Houve uma associação entre o uso de cinco ou mais medicamentos e possíveis interações droga-droga (p = 0.000), e entre o período de tempo de terapia antirretroviral acima de seis anos e possíveis interações droga-droga (p terapia antirretroviral. un estudio transversal se llevó a cabo en 161 adultos con infección por VIH. Se recogieron datos clínicos, socio demográficos, y de tratamiento antirretroviral. Para analizar las posibles

  18. Progress in Psoriasis Therapy via Novel Drug Delivery Systems.

    Science.gov (United States)

    Vincent, Nitha; Ramya, Devi D; Vedha, Hari Bn

    2014-02-17

    Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient's quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.

  19. Computer-Aided Optimization of Combined Anti-Retroviral Therapy for HIV: New Drugs, New Drug Targets and Drug Resistance.

    Science.gov (United States)

    Zazzi, Maurizio; Cozzi-Lepri, Alessandro; Prosperi, Mattia C F

    2016-01-01

    Resistance to antiretroviral drugs is a complex and evolving area with relevant implications in the treatment of human immunodeficiency virus (HIV) infection. Several rules, algorithms and full-fledged computer programs have been developed to assist the HIV specialist in the choice of the best patient-tailored therapy. Experts' rules and statistical/machine learning algorithms for interpreting HIV drug resistance, along with their program implementations, were retrieved from PubMed and other on-line resources to be critically reviewed in terms of technical approach, performance, usability, update, and evolution (i.e. inclusion of novel drugs or expansion to other viral agents). Several drug resistance prediction algorithms for the nucleotide/nucleoside/non-nucleoside reverse transcriptase, protease and integrase inhibitors as well as coreceptor antagonists are currently available, routinely used, and have been validated thoroughly in independent studies. Computer tools that combine single-drug genotypic/phenotypic resistance interpretation and optimize combination antiretroviral therapy have been also developed and implemented as web applications. Most of the systems have been updated timely to incorporate new drugs and few have recently been expanded to meet a similar need in the Hepatitis C area. Prototype systems aiming at predicting virological response from both virus and patient indicators have been recently developed but they are not yet being routinely used. Computing HIV genotype to predict drug susceptibility in vitro or response to combination antiretroviral therapy in vivo is a continuous and productive research field, translating into successful treatment decision support tools, an essential component of the management of HIV patients.

  20. Autonomous targeting of infectious superspreaders using engineered transmissible therapies.

    Directory of Open Access Journals (Sweden)

    Vincent T Metzger

    2011-03-01

    Full Text Available Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk 'superspreader' populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition, and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals--analogous to 'transmissible immunization' that occurs with live-attenuated vaccines (but without the potential for reversion to virulence. Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.

  1. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@yahoo.com [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Chen Yiru [National Yang-Ming University, Department of Biomedical Engineering (China); He Wenjie; Hong Poda [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem (Israel)

    2013-01-15

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe{sup 2+} solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  2. RNA Editing and Drug Discovery for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wei-Hsuan Huang

    2013-01-01

    Full Text Available RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized.

  3. Drug Discovery of Therapies for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Blat, Yuval; Blat, Shachar

    2015-12-01

    Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by the loss of the muscle protein, dystrophin, leading to progressive loss of muscle fibers and muscle weakness. Drug discovery efforts targeting DMD have used two main approaches: (1) the restoration of dystrophin expression or the expression of a compensatory protein, and (2) the mitigation of downstream pathological mechanisms, including dysregulated calcium homeostasis, oxidative stress, inflammation, fibrosis, and muscle ischemia. The aim of this review is to introduce the disease, its pathophysiology, and the available research tools to a drug discovery audience. This review will also detail the most promising therapies that are currently being tested in clinical trials or in advanced preclinical models. © 2015 Society for Laboratory Automation and Screening.

  4. Pattern of drug therapy problems and interventions in ambulatory patients receiving antiretroviral therapy in Nigeria

    Directory of Open Access Journals (Sweden)

    Ojeh VB

    2015-06-01

    Full Text Available Objectives: We describe the frequency and types of drug therapy problems (DTPs, and interventions carried out to resolve them, among a cohort of HIV- infected patients on ART in Jos, Nigeria. Methods: A prospective pharmacists’ intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH. Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. Results: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions were made to resolve DTPs in 401 (4.3% patients with a mean age of 41 (SD=10 years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%, unnecessary drug (n=55, 13.1% and wrong drug indication (n=55, 13.1%. Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%, rectification of incomplete prescriptions (n=85, 20.2%, change of drug or dosage (n=67, 16.0%, and discontinuation of the offending drug (n=59, 14.0%. A total of 389 (93% out of 420 of the recommendations were accepted. In all, 50.4% (212 of the problematic prescriptions were changed and dispensed, 22.2% (89 were clarified and dispensed, while wrong identities were corrected in 11.7% (49. However, 7.5% (30 prescriptions were dispensed as prescribed, 5.2% (21 were not dispensed, and 3% (12 were unresolved. Conclusion: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors.

  5. [Experimental therapy of cardiac remodeling with quercetin-containing drugs].

    Science.gov (United States)

    Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

    2013-01-01

    It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

  6. Longterm maintenance therapy with disease modifying antirheumatic drugs.

    Science.gov (United States)

    Capell, Hilary

    2002-11-01

    Longterm safety and efficacy of disease modifying antirheumatic drugs (DMARD) have been challenging to assess. There are few studies that have evaluated patient outcome beyond 5 years. As patients may receive several DMARD over the course of their disease a long with nonsteroidal antiinflammatory drugs, corticosteroids, and other drugs for comorbidities, it is difficult to design and implement a trial to define a specific drug's longterm effect. Based on the findings of several key studies, however, it does appear that DMARD are safe when taken longterm, and that they are more likely to be discontinued because of inefficacy than toxicity. Although DMARD are often discontinued because of lack of efficacy, 12 year data suggest that DMARD can provide benefit over this period. The toxicity profiles vary significantly between DMARD. In addition, the time during therapy when the majority of these adverse effects most frequently appear is DMARD-specific. Prospective studies are needed to further clarify longterm safety and efficacy of the newer DMARD.

  7. Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy.

    Science.gov (United States)

    Fasinu, Pius S; Gurley, Bill J; Walker, Larry A

    2015-01-01

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy).

  8. Treating adolescent drug abuse: a randomized trial comparing multidimensional family therapy and cognitive behavior therapy.

    Science.gov (United States)

    Liddle, Howard A; Dakof, Gayle A; Turner, Ralph M; Henderson, Craig E; Greenbaum, Paul E

    2008-10-01

    To examine the efficacy of two adolescent drug abuse treatments: individual cognitive behavioral therapy (CBT) and multidimensional family therapy (MDFT). A 2 (treatment condition) x 4 (time) repeated-measures intent-to-treat randomized design. Data were gathered at baseline, termination, 6 and 12 months post-termination. Analyses used latent growth curve modeling. Community-based drug abuse clinic in the northeastern United States. A total of 224 youth, primarily male (81%), African American (72%), from low-income single-parent homes (58%) with an average age of 15 years were recruited into the study. All youth were drug users, with 75% meeting DSM-IV criteria for cannabis dependence and 13% meeting criteria for abuse. Five outcomes were measured: (i) substance use problem severity; (ii) 30-day frequency of cannabis use; (iii) 30-day frequency of alcohol use; (iv) 30-day frequency of other drug use; and (v) 30-day abstinence. Both treatments produced significant decreases in cannabis consumption and slightly significant reductions in alcohol use, but there were no treatment differences in reducing frequency of cannabis and alcohol use. Significant treatment effects were found favoring MDFT on substance use problem severity, other drug use and minimal use (zero or one occasion of use) of all substances, and these effects continued to 12 months following treatment termination. Both interventions are promising treatments. Consistent with previous controlled trials, MDFT is distinguished by the sustainability of treatment effects.

  9. Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Elena Nikolayevna Aleksandrova

    2014-01-01

    Full Text Available Significant progress in treating immunoinflammatory rheumatic diseases (RD is related to the design of a novel family of drugs, genetically engineered (GE drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept, anti-B-cell drugs (rituximab, belimumab, interleukin-6 receptor antagonist (tocilizumab, and T-cell costimulation blocker (abatacept have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.

  10. Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Elena Nikolayevna Aleksandrova

    2014-03-01

    Full Text Available Significant progress in treating immunoinflammatory rheumatic diseases (RD is related to the design of a novel family of drugs, genetically engineered (GE drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept, anti-B-cell drugs (rituximab, belimumab, interleukin-6 receptor antagonist (tocilizumab, and T-cell costimulation blocker (abatacept have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.

  11. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

    Directory of Open Access Journals (Sweden)

    Michaela Thomas

    2017-11-01

    Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

  12. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening.

    Science.gov (United States)

    Thomas, Michaela; Willerth, Stephanie M

    2017-01-01

    Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone), and poly(ethylene glycol). This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

  13. Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection.

    Science.gov (United States)

    Soudy, R; Byeon, N; Raghuwanshi, Y; Ahmed, S; Lavasanifar, A; Kaur, K

    2017-01-01

    Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide- receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Engineered sodium hyaluronate respirable dry powders for pulmonary drug delivery.

    Science.gov (United States)

    Martinelli, Francesco; Balducci, Anna Giulia; Kumar, Abhinav; Sonvico, Fabio; Forbes, Ben; Bettini, Ruggero; Buttini, Francesca

    2017-01-30

    Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0-66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine>stearyl alcohol>cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol>cetostearyl alcohol>stearylamine with LC50 of 24.7, 13.2 and 1.8μg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  15. Generalized lichenoid drug eruption associated with imatinib mesylate therapy

    Directory of Open Access Journals (Sweden)

    Sudip Kumar Ghosh

    2013-01-01

    Full Text Available Imatinib mesylate (IM, an anticancer drug, has been widely used to treat chronic myeloid leukemia (CML, gastrointestinal stromal tumors (GIST, and dermato-fibrosarcoma protuberans. Cutaneous reactions to IM have been reported to occur in varying number of patients in different case series. Non-lichenoid cutaneous reactions secondary to IM have been well-documented in the literature and are the commonest non-hematologic adverse reactions associated with its use. Lichenoid drug eruption (LDE associated with IM therapy has rarely been reported in the literature. A case of a generalized LDE associated with IM therapy has been described here for its rarity and interesting clinical presentation. As the clinical usage of IM is increasing, one might expect an increasing number of similar patients in the future. It is thus important to realize the potential of IM to produce LDE and to differentiate this entity from idiopathic lichen planus. In the present article, the reports of IM-associated LDE, described in the PubMed and Medline database (in English language literature, have also been reviewed.

  16. Genetic engineering of stem cells for enhanced therapy.

    Science.gov (United States)

    Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

    2013-01-01

    Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

  17. A study of the frequency and pattern of non-drug therapies among ...

    African Journals Online (AJOL)

    Background: Since complications and therapeutic failures are common with cardiovascular diseases, it became necessary to assess the pattern of Non-drug therapies as a tool in enhancing the outcome of therapy. Aim: To assess the frequency of Non-drug therapies among patients with some cardiovascular diseases in the ...

  18. Progress in psoriasis therapy via novel drug delivery systems

    Directory of Open Access Journals (Sweden)

    Nitha Vincent

    2014-09-01

    Full Text Available Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.

  19. Identification of Drug Therapy Problems among Elderly in-patients of ...

    African Journals Online (AJOL)

    The aim of this study was to investigate the occurrence of drug related problems among elderly in-patients and to identify those at risk of DTPs. ... major Polypharmacy 60 (66.7%), unnecessary drug therapy 29 (32.2%), adverse drug reactions 28 (31.1%), need for additional therapy 27 (30%) and non compliance 13 (14.4%).

  20. Clinically important ocular reactions to systemic drug therapy.

    Science.gov (United States)

    Rennie, I G

    1993-09-01

    Many systemically administered drugs produce ocular adverse effects. Fortunately, relatively few are capable of causing significant, irreversible visual impairment. It is the responsibility of every clinician when prescribing systemic therapeutic agents to be aware of potential adverse ocular reactions, to appreciate their significance, and to inform the patient of the potential risks of treatment. In instances where serious adverse reactions relate to the cumulative effects of prolonged treatment, it is the responsibility of the prescribing physician to institute appropriate methods of visual screening. In this respect, it is most important to obtain the necessary individual baseline measurements before treatment is commenced. Chloroquine retinopathy is probably the most feared of all adverse ocular reactions to systemic drug therapy. However, it occurs only rarely if the daily dosage of chloroquine does not exceed 250mg. Regular screening using automated perimetry is mandatory if prolonged therapy is contemplated. Amiodarone almost inevitably produces corneal deposits. These rarely produce symptoms, and resolve upon withdrawal of the drug. Optic neuropathy has recently been described with amiodarone. Systemic anticoagulant therapy may be associated with intraocular hemorrhage in patients with pre-existing disciform macular degeneration, and such agents should be used with caution in affected individuals. Systemic corticosteroids produce posterior subcapsular cataracts in susceptible individuals which may profoundly affect visual acuity. Although elevated intraocular pressure may also result from systemic therapy, the relationship between the pressure rise and development of glaucomatous changes remains unclear. Ethambutol may produce optic neuropathy if the daily dosage exceeds 15 mg/kg. The changes are usually reversible within a few weeks of stopping treatment. High doses of tamoxifen may produce a maculopathy with loss of visual acuity, if given for prolonged

  1. Genetic engineering and therapy for inherited and acquired cardiomyopathies.

    Science.gov (United States)

    Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

    2006-10-01

    The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

  2. Challenges and future in vaccines, drug development, and immunomodulatory therapy.

    Science.gov (United States)

    Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

    2014-08-01

    Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

  3. 77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

    Science.gov (United States)

    2012-05-07

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship Educational Workshop: Redefining the `C' in CGMP: Creating, Implementing, and Sustaining a Culture of Compliance AGENCY: Food and Drug Administration, HHS. ] ACTION: Notice of...

  4. 78 FR 26375 - Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship...

    Science.gov (United States)

    2013-05-06

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship Educational Workshop: Redefining the `C' in CGMP (Current Good... Administration, HHS. ACTION: Notice of public conference. The Food and Drug Administration (FDA), in co...

  5. Genetically engineered biological agents in therapy for systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Elena Aleksandrovna Aseeva

    2013-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.

  6. Repurposing of gallium-based drugs for antibacterial therapy.

    Science.gov (United States)

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

    2014-01-01

    While the occurrence and spread of antibiotic resistance in bacterial pathogens is vanishing current anti-infective therapies, the antibiotic discovery pipeline is drying up. In the last years, the repurposing of existing drugs for new clinical applications has become a major research area in drug discovery, also in the field of anti-infectives. This review discusses the potential of repurposing previously approved gallium formulations in antibacterial chemotherapy. Gallium has no proven function in biological systems, but it can act as an iron-mimetic in both prokaryotic and eukaryotic cells. The activity of gallium mostly relies on its ability to replace iron in redox enzymes, thus impairing their function and ultimately hampering cell growth. Cancer cells and bacteria are preferential gallium targets due to their active metabolism and fast growth. The wealth of knowledge on the pharmacological properties of gallium has opened the door to the repurposing of gallium-based drugs for the treatment of infections sustained by antibiotic-resistant bacterial pathogens, such as Acinetobacter baumannii or Pseudomonas aeruginosa, and for suppression of Mycobacterium tuberculosis growth. The promising antibacterial activity of gallium both in vitro and in different animal models of infection raises the hope that gallium will confirm its efficacy in clinical trials, and will become a valuable therapeutic option to cure otherwise untreatable bacterial infections. © 2014 International Union of Biochemistry and Molecular Biology.

  7. Development of drug delivery systems for radionuclide therapy using a combination therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, On Hee; Choi, Sun Ju [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2005-07-01

    For the development of new controlled drug delivery systems, the application of combination therapy using angiogenesis inhibitor and tumor static agents has drawn great attention. This approach would be very beneficial for cancer treatment especially when a new drug deliver system utilizing biodegradable polymers is developed. Therefore, the present study for the combination therapy of angiogenesis inhibitor and chemotherapeutic agents was to carry out prior to the development of the novel drug delivery. In present study, the ability of inhibition on cell growth was investigated with treatment of anti-angiogenetic agent and anticancer agent. Thalidomide was used as an antivasculatory agents and Doxorubicine was treated as a chemotherapeutic agent. To demonstrate apoptotic process in in-vitro study, TUNEL assay was carried out. Also, the alteration of p53 level was examined by using western blotting. For the cell lines, NIH:OVCAR3, MKN45, SNU719, C6, L929, T98G, Hep3B and Calu6 were applied. Results showed that Thalidomide inhibited cell growth in tumor cell lines in a dose-dependent manner and Doxorubicin as well. A significant synergistic effect on the apoptotic was noticed in the combination treatment of Thalidomide and Doxorubicin compared to a single treatment of either drug. Therefore, it can be concluded that the mechanism of cytotoxicity was due to the enhancement of apoptosis in early cell death with combination treatment in tumor cell lines.

  8. Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs

    Directory of Open Access Journals (Sweden)

    Jonathan M. Brunger

    2017-05-01

    Full Text Available Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1 and tumor necrosis factor α (TNF-α. Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. The customization of intrinsic cellular signaling pathways in stem cells, as demonstrated here, opens innovative possibilities for safer and more effective therapeutic approaches for a wide variety of diseases.

  9. VisANT 4.0: Integrative network platform to connect genes, drugs, diseases and therapies.

    Science.gov (United States)

    Hu, Zhenjun; Chang, Yi-Chien; Wang, Yan; Huang, Chia-Ling; Liu, Yang; Tian, Feng; Granger, Brian; Delisi, Charles

    2013-07-01

    With the rapid accumulation of our knowledge on diseases, disease-related genes and drug targets, network-based analysis plays an increasingly important role in systems biology, systems pharmacology and translational science. The new release of VisANT aims to provide new functions to facilitate the convenient network analysis of diseases, therapies, genes and drugs. With improved understanding of the mechanisms of complex diseases and drug actions through network analysis, novel drug methods (e.g., drug repositioning, multi-target drug and combination therapy) can be designed. More specifically, the new update includes (i) integrated search and navigation of disease and drug hierarchies; (ii) integrated disease-gene, therapy-drug and drug-target association to aid the network construction and filtering; (iii) annotation of genes/drugs using disease/therapy information; (iv) prediction of associated diseases/therapies for a given set of genes/drugs using enrichment analysis; (v) network transformation to support construction of versatile network of drugs, genes, diseases and therapies; (vi) enhanced user interface using docking windows to allow easy customization of node and edge properties with build-in legend node to distinguish different node type. VisANT is freely available at: http://visant.bu.edu.

  10. Mitochondrial ROS and cancer drug resistance: Implications for therapy.

    Science.gov (United States)

    Okon, Imoh S; Zou, Ming-Hui

    2015-10-01

    Under physiological conditions, a well-coordinated and balanced redox system exists to ensure that reactive oxygen species (ROS) are appropriately utilized to accomplish specific functions, such as signaling and protein regulation. The influence of ROS within malignant cells, whether for good or bad may depend on several factors, such as tumor and tissue type, disease stage, treatment strategy, as well as duration, specificity and levels of ROS. What then are the known roles of ROS in cancer? Firstly, ROS significantly impacts cancer phenotypes. Secondly, the oxidative ROS property responsible for killing cancer cells, also impact secondary signaling networks. Thirdly, a strong correlation exist between ROS and genetic instability which may promote mutations. Finally, emerging observations suggest a role for mitochondrial ROS in cancer drug resistance, with implications for therapy. The mitochondria is a key regulator of metabolic-redox (meta-redox) alterations within cancer cells. Like a double-edged sword, mitochondrial ROS perturbations in cancer therapy may be beneficial or detrimental. However, harnessing ROS-specific cancer-targeting benefits remain a major challenge. Published by Elsevier Ltd.

  11. Gastrointestinal traits: individualizing therapy for obesity with drugs and devices.

    Science.gov (United States)

    Camilleri, Michael; Acosta, Andres

    2016-01-01

    The aims of this article were to review the discrepancy between numbers of people requiring weight loss treatment and results and to assess the potential effects of pharmacologic treatments (recently approved for obesity) and endoscopically deployed devices on quantitative GI traits in development for obesity treatment. We conducted a review of relevant literature to achieve our objectives. The 2013 guidelines increased the number of adults recommended for weight loss treatment by 20.9% (116.0 million to 140.2 million). There is an imbalance between efficacy and costs of commercial weight loss programs and drug therapy (average weight loss about 5 kg). The number of bariatric procedures performed in the United States has doubled in the past decade. The efficacy of bariatric surgery is attributed to reduction in the volume of the stomach, nutrient malabsorption with some types of surgery, increased postprandial incretin responses, and activation of farnesoid X receptor mechanisms. These GI and behavioral traits identify sub-phenotypes of obesity, based on recent research. The mechanisms or traits targeted by drug and device treatments include centrally mediated alterations of appetite or satiation, diversion of nutrients, and alteration of stomach capacity, gastric emptying, or incretin hormones. Future treatment may be individualized based on quantitative GI and behavioral traits measured in obese patients. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  12. Giant cell arteritis. Part III. New trends in its treatment (role of genetically engineered drugs

    Directory of Open Access Journals (Sweden)

    Azamat Makhmudovich Satybaldyev

    2013-01-01

    Full Text Available Giant cell arteritis (GCA is a well-known vasculitis sensitive to glucocorticoid (GC immuno-suppression. However, during long-term treatment there may be many adverse reactions that remain a serious problem so far. Since GCA encompasses a broad spectrum of clinical subtypes, ranging from severe visual loss and neurological deficits to isolated systemic signs, its treatment must be adjusted specially to each case. The literature contains contradicting recommendations for the therapy for GCA. The paper considers different treatment options for GCA, including that with neuro-ophthalmic and neurological complications, as well as the evidence for their possible adjuvant therapies. Although there is no randomized controlled clinical trial in GCA with ocular and neurological complications, the data available in the literature suggest that these patients are recommended to be admitted for high-dose intravenous methylprednisolone, monitoring, and prevention of GC-induced complications. It is expedient to use aspirin in these cases. The evidence supporting the use of methotrexate, as well as genetically engineered agents (GEAs, infliximab, etanercept as steroid-sparing agents is discussed. Cases of using individual GEAs (adalimumab, tocilizumab and rituximab as an alternative to GC monotherapy are described. It is concluded that there is a need for extended clinical trials evaluating the most effective and safe GC-sparing drugs.

  13. Drug dosing during intermittent hemodialysis and continuous renal replacement therapy : special considerations in pediatric patients.

    Science.gov (United States)

    Veltri, Michael A; Neu, Alicia M; Fivush, Barbara A; Parekh, Rulan S; Furth, Susan L

    2004-01-01

    Chronic renal failure is, fortunately, an unusual occurrence in children; however, many children with various underlying illnesses develop acute renal failure, and transiently require renal replacement therapy - peritoneal dialysis, intermittent hemodialysis (IHD), or continuous renal replacement therapy (CRRT). As children with acute and chronic renal failure often have multiple comorbid conditions requiring drug therapy, generalists, intensivists, nephrologists, and pharmacists need to be aware of the issues surrounding the management of drug therapy in pediatric patients undergoing renal replacement therapy. This article summarizes the pharmacokinetics and dosing of many drugs commonly prescribed for pediatric patients, and focuses on the management of drug therapy in pediatric patients undergoing IHD and CRRT in the intensive care unit setting. Peritoneal dialysis is not considered in this review. Finally, a summary table with recommended initial dosages for drugs commonly encountered in pediatric patients requiring IHD or CRRT is presented.

  14. Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

    Science.gov (United States)

    Hasan, Anwarul; Waters, Renae; Roula, Boustany; Dana, Rahbani; Yara, Seif; Alexandre, Toubia; Paul, Arghya

    2016-07-01

    Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Effects of aerobic exercise and drug therapy on blood pressure and ...

    African Journals Online (AJOL)

    They were randomly assigned to drug therapy (Normoretic: Hydrochlorothiazide + amiloride hydrochloride, and Amlodipine) (control: n=33) and aerobic dance combined with drug therapy (exercise: n=30) groups. Intervention in each group lasted 12 weeks. BP was measured at baseline and during and pos-intervention.

  16. Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin.

    Science.gov (United States)

    Prausnitz, Mark R

    2017-06-07

    Microneedle patches (MNPs) contain arrays of solid needles measuring hundreds of microns in length that deliver drugs and vaccines into skin in a painless, easy-to-use manner. Optimal MNP design balances multiple interdependent parameters that determine mechanical strength, skin-insertion reliability, drug delivery efficiency, painlessness, manufacturability, and other features of MNPs that affect their performance. MNPs can be made by adapting various microfabrication technologies for delivery of small-molecule drugs, biologics, and vaccines targeted to the skin, which can have pharmacokinetic and immunologic advantages. A small number of human clinical trials, as well as a large and growing market for MNP products for cosmetics, indicate that MNPs can be used safely, efficaciously, and with strong patient acceptance. More advanced clinical trials and commercial-scale manufacturing will facilitate development of MNPs to realize their potential to dramatically increase patient access to otherwise-injectable drugs and to improve drug performance via skin delivery.

  17. Layer-by-layer assembled multilayers and polymeric nanoparticles for drug delivery in tissue engineering applications

    Science.gov (United States)

    Mehrotra, Sumit

    Tissues and organs in vivo are structured in three dimensional (3-D) ordered assemblies to maintain their metabolic functions. In the case of an injury, certain tissues lack the regenerative abilities without an external supportive environment. In order to regenerate the natural in vivo environment post-injury, there is a need to design three-dimensional (3-D) tissue engineered constructs of appropriate dimensions along with strategies that can deliver growth factors or drugs at a controlled rate from such constructs. This thesis focuses on the applications of hydrogen bonded (H-bonded) nanoscale layer-by-layer (LbL) assembled multilayers for time controlled drug delivery, fabrication of polymeric nanoparticles as drug delivery carriers, and engineering 3-D cellular constructs. Axonal regeneration in the central nervous system after spinal cord injury is often disorganized and random. To support linear axonal growth into spinal cord lesion sites, certain growth factors, such as brain-derived neurotrophic factor (BDNF), needs to be delivered at a controlled rate from an array of uniaxial channels patterned in a scaffold. In this study, we demonstrate for the first time that H-bonded LbL assembled degradable thin films prepared over agarose hydrogel, whereby the protein was loaded separately from the agarose fabrication, provided sustained release of protein under physiological conditions for more than four weeks. Further, patterned agarose scaffolds implanted at the site of a spinal cord injury forms a reactive cell layer of leptomeningeal fibroblasts in and around the scaffold. This limits the ability of axons to reinnervate the spinal cord. To address this challenge, we demonstrate the time controlled release of an anti-mitotic agent from agarose hydrdgel to control the growth of the reactive cell layer of fibroblasts. Challenges in tissue engineering can also be addressed using gene therapy approaches. Certain growth factors in the body are known to inhibit

  18. [Infants of drug-addicted mothers: pitfalls of replacement therapy].

    Science.gov (United States)

    Vert, Paul; Hamon, Isabelle; Hubert, Claire; Legagneur, Michel; Hascoet, Jean-Michel

    2008-05-01

    Maternal drug addiction can cause problems for the fetus and the newborn, and hamper long-term development. The prevalence of drug addiction during pregnancy varies from 1 % to more than 10 % depending on the country and the maternity unit. Management of these mothers can be further complicated by medical, social and psychological problems. Compared to methadone, heroin replacement therapy with buprenorphine provides better stabilization of the mother and causes fewer withdrawal symptoms in the newborn. Despite numerous publications on the effects of this partly preventive medication, data on buprenorphine pharmacology at birth are scarce. In this study, 20 newborns of mothers using oral buprenorphine were observed until the end of the withdrawal syndrome, when present. Buprenorphine plasma levels were determined with HPLC and mass spectrometry in the mother at delivery and in the newborn at birth (cord blood), 24 and 48 hours. Fifteen newborns were born at term (mean +/- SD birth weight 3029 +/- 273 g), and the other five between 32 and 36 weeks. All Apgar scores were > or =7. Withdrawal symptoms were observed in 8 of the 15 infants born to mothers taking buprenorphine alone, and lasted between 5 and 35 days. The newborns were classified in three groups. Groups I (N8) and II (N7) comprised newborns with and without withdrawal symptoms, respectively. In group III (N5), the mothers were polyintoxicated (as shown by urinary drug or neurotropic substance screening) and the newborns were symptomatic for 1 to 69 days. Buprenorphine plasma levels in the mothers ranged from 0 to 2.9 microg/L, suggesting large differences in adherence. At birth there was no significant difference in the mean plasma buprenorphine level between newborns with and without withdrawal symptoms; the respective values were 0.7 (0.4-1.3) and 0.5 (0-0.6) microg/L. In asymptomatic newborns (group II), buprenorphine was no longer detectable at 48 h, whereas in symptomatic newborns (group I), the mean

  19. A Smart, Photocontrollable Drug Release Nanosystem for Multifunctional Synergistic Cancer Therapy.

    Science.gov (United States)

    Yi, Yi; Wang, Huijing; Wang, Xuewei; Liu, Qiaoling; Ye, Mao; Tan, Weihong

    2017-02-22

    Multifunctional synergistic therapy holds promise in biomedical studies and clinical practice. However, strategies aimed at easily integrating the components of such multimodal therapies are needed. Therefore, we herein report a smart drug release nanosystem able to perform photodynamic therapy, photothermal therapy and chemotherapy in a photocontrollable manner. Doxorubicin (DOX), a chemotherapy drug, and 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4), a photosensitizer, were physically intercalated into a DNA assembly immobilized on gold nanorods. The drugs were efficiently delivered to target cells and released under light irradiation, resulting in a synergism that combined phototherapy and chemotherapy for cancer treatment. This smart, photocontrollable drug release nanosystem promises precisely controlled drug release for multifunctional synergistic cancer therapy.

  20. [Morbidity spectrum and drug therapy of homeless persons in Munich].

    Science.gov (United States)

    Egen, V

    1998-01-01

    In Germany there are currently approx. 200,000 homeless single people, and the trend is rising. As a result of the situation in which they find themselves, many of these persons are ill and in need of medical treatment. A study was performed in Munich/Germany, focussing on a medical practice providing care for the homeless, to investigate their illnesses and pharmacological therapy. The medical practice was located in a municipal shelter. Each year about 350 different destitute homeless men--about 15 per cent of all single homeless people in Munich--were cared for. The men, whose ages ranged from about 17 to 74 years were single and the majority lived in shelters, bed and breakfast accommodations, or shared apartments. About ten per cent lived on the street. For the study, 171 randomly selected medical records were analysed for the period of July 1994 to June 1995. The homeless men suffered principally from the following illnesses: psychiatric illnesses (36%), infectious and parasitic diseases (31%), skin diseases (30%), injuries (29%), diseases of the skeleton, of the muscles and of the connective tissues (28%), diseases of the respiratory organs (27%), cardiovascular diseases (24%), and diseases of the digestive organs (17%). Seventy-five per cent of the patients received drug treatment. In the case of 37% of the patients, wounds were treated and dressed in the medical practice itself. The most frequently prescribed drugs were: analgesics (12%), antibiotics (10%), antihypertensives (10%), gastrointestinal treatments (9%), treatments for colds (9%), and dermatopharmacological preparations (6%). It was surprising that only 16% of the psychic ill patients were treated with drugs, while over 60% of the other illnesses were mostly treated pharmacologically. The interaction with alcohol was the reason for that. The study showed that the practice did not sufficiently reach women and homeless people living on the street. The homeless situation, the personal and social

  1. [Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

    Science.gov (United States)

    Gou, Q Y; Yu, R B; Shi, R H

    2017-05-10

    Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter (H.) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

  2. Immediate and Delayed Drug Therapy Effects on Low Dose Sarin Exposed Mice Myocardial Performance

    Science.gov (United States)

    2011-03-01

    antiarrhythmic drug which acts as a β-adrenergic receptor blockade (Ramos, et al. 2003). Major benefits of propranolol are reduced heart rate, decrease...IMMEDIATE AND DELAYED DRUG THERAPY EFFECTS ON LOW DOSE SARIN EXPOSED MICE MYOCARDIAL PERFORMANCE THESIS Joshua T. Miller, Major, USA...IMMEDIATE AND DELAYED DRUG THERAPY EFFECTS ON LOW DOSE SARIN EXPOSED MICE MYOCARDIAL PERFORMANCE THESIS Presented to the Faculty Department of

  3. Identifying enriched drug fragments as possible candidates for metabolic engineering

    OpenAIRE

    Sharma, Sunandini; Karri, Kritika; Thapa, Ishwor; Bastola, Dhundy; Ghersi, Dario

    2016-01-01

    Background Fragment-based approaches have now become an important component of the drug discovery process. At the same time, pharmaceutical chemists are more often turning to the natural world and its extremely large and diverse collection of natural compounds to discover new leads that can potentially be turned into drugs. In this study we introduce and discuss a computational pipeline to automatically extract statistically overrepresented chemical fragments in therapeutic classes, and searc...

  4. Implanted cardioverter-defibrillators are preferable to drugs as primary therapy in sustained ventricular tachyarrhythmias.

    Science.gov (United States)

    Saksena, S; Madan, N; Lewis, C

    1996-01-01

    The choice of initial therapy for patients with malignant ventricular tachyarrhythmias is examined based on clinical efficacy, patient safety, and cost. Antiarrhythmic drug therapy can be administered using a guided or empiric approach. Guided type-1 antiarrhythmic drug therapy has been associated with high arrhythmia recurrence rates (> 40% at 1 year) and moderate sudden death rates (10% at 1 year). Sotalol is associated with lower arrhythmia recurrence rates (20% at 1 year) that increase to 50% at 4 years. Beta-blocking agents have a limited role as stand-alone therapy in this condition. Empiric amiodarone therapy has sudden death-free survival rates of 82% at 2 years but has significantly poorer results in patients with ejection fractions death recurrence rates of 1% to 2% per year, with a cumulative index of 10% at 5 years. Total survival rate of ICD recipients ranges from 85% to 92% at 2 years. In patients with good left ventricular function, it approaches 90% at 5 years, whereas it is between 50% to 60% in patients with severe left ventricular dysfunction. Data from device memory indicate an absolute reduction in mortality rates with ICD intervention. Comparison of drug and device therapy has been performed in retrospective and prospective studies. Improved survival with device therapy is noted, particularly in patients with ejection fractions rate of ICD therapy of 0.8% contrasts favorably with a 13% mortality rate in the ESVEM trial with antiarrhythmic drugs and a 3.5% mortality rate in the CASCADE study. Economic analyses show that drug therapy and device therapy are both within the range of other current cardiovascular therapies. An improving economic profile for device therapy has been observed with nonthoracotomy and pectoral implantation and direct use of ICD therapy because primary therapy shortens hospital stay and reduces costs. Based on available data, ICD therapy is preferable as initial therapy in patients with malignant ventricular

  5. Protein Kinases as Drug Development Targets for Heart Disease Therapy

    Directory of Open Access Journals (Sweden)

    Alison L. Müller

    2010-07-01

    Full Text Available Protein kinases are intimately integrated in different signal transduction pathways for the regulation of cardiac function in both health and disease. Protein kinase A (PKA, Ca2+-calmodulin-dependent protein kinase (CaMK, protein kinase C (PKC, phosphoinositide 3-kinase (PI3K and mitogen-activated protein kinase (MAPK are not only involved in the control of subcellular activities for maintaining cardiac function, but also participate in the development of cardiac dysfunction in cardiac hypertrophy, diabetic cardiomyopathy, myocardial infarction, and heart failure. Although all these kinases serve as signal transducing proteins by phosphorylating different sites in cardiomyocytes, some of their effects are cardioprotective whereas others are detrimental. Such opposing effects of each signal transduction pathway seem to depend upon the duration and intensity of stimulus as well as the type of kinase isoform for each kinase. In view of the fact that most of these kinases are activated in heart disease and their inhibition has been shown to improve cardiac function, it is suggested that these kinases form excellent targets for drug development for therapy of heart disease.

  6. Diabetes Insipidus: A Challenging Diagnosis with New Drug Therapies

    Science.gov (United States)

    Saifan, Chadi; Nasr, Rabih; Mehta, Suchita; Sharma Acharya, Pranab; Perrera, Isera; Faddoul, Giovanni; Nalluri, Nikhil; Kesavan, Mayurakhan; Azzi, Yorg; El-Sayegh, Suzanne

    2013-01-01

    Diabetes Insipidus (DI) is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic). Drug induced DI is a well-known entity with an extensive list of medications. Polyuria is generally defined as urine output exceeding 3 liters per day in adults. It is crucial to identify the cause of diabetes insipidus and to implement therapy as early as possible to prevent the electrolyte disturbances and the associated mortality and morbidity. It is very rare to have an idiosyncratic effect after a short use of a medication, and physicians should be aware of such a complication to avoid volume depletion. The diagnosis of diabetes insipidus is very challenging because it relies on laboratory values, urine output, and the physical examination of the patient. A high clinical suspicion of diabetes insipidus should be enough to initiate treatment. The complications related to DI are mostly related to the electrolyte imbalance that can affect the normal physiology of different organ systems. PMID:24977135

  7. Collaborative drug therapy management and comprehensive medication management-2015.

    Science.gov (United States)

    McBane, Sarah E; Dopp, Anna L; Abe, Andrew; Benavides, Sandra; Chester, Elizabeth A; Dixon, Dave L; Dunn, Michaelia; Johnson, Melissa D; Nigro, Sarah J; Rothrock-Christian, Tracie; Schwartz, Amy H; Thrasher, Kim; Walker, Scot

    2015-04-01

    The American College of Clinical Pharmacy (ACCP) previously published position statements on collaborative drug therapy management (CDTM) in 1997 and 2003. Since 2003, significant federal and state legislation addressing CDTM has evolved and expanded throughout the United States. CDTM is well suited to facilitate the delivery of comprehensive medication management (CMM) by clinical pharmacists. CMM, defined by ACCP as a core component of the standards of practice for clinical pharmacists, is designed to optimize medication-related outcomes in collaborative practice environments. New models of care delivery emphasize patient-centered, team-based care and increasingly link payment to the achievement of positive economic, clinical, and humanistic outcomes. Hence clinical pharmacists practicing under CDTM agreements or through other privileging processes are well positioned to provide CMM. The economic value of clinical pharmacists in team-based settings is well documented. However, patient access to CMM remains limited due to lack of payer recognition of the value of clinical pharmacists in collaborative care settings and current health care payment policy. Therefore, the clinical pharmacy discipline must continue to establish and expand its use of CDTM agreements and other collaborative privileging mechanisms to provide CMM. Continued growth in the provision of CMM by appropriately qualified clinical pharmacists in collaborative practice settings will enhance recognition of their positive impact on medication-related outcomes. © 2015 Pharmacotherapy Publications, Inc.

  8. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy

    DEFF Research Database (Denmark)

    Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris

    2013-01-01

    . This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible...

  9. Engineering

    National Research Council Canada - National Science Library

    Includes papers in the following fields: Aerospace Engineering, Agricultural Engineering, Chemical Engineering, Civil Engineering, Electrical Engineering, Environmental Engineering, Industrial Engineering, Materials Engineering, Mechanical...

  10. REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

    Directory of Open Access Journals (Sweden)

    BROSCATEAN, Emanuela-Flavia

    2013-12-01

    Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As

  11. Special issue: engineering toxins for 21st-century therapies: introduction.

    Science.gov (United States)

    Acharya, K Ravi

    2011-12-01

    This special issue on 'Engineering toxins for 21st century therapies' provides a critical review of the current state of multifaceted aspects of toxin research by some of the leading researchers in the field. It also highlights the clinical potential and challenges for development of novel biologics based on engineered toxin derived products. © 2011 The Author Journal compilation © 2011 FEBS.

  12. Role of gene therapy in tissue engineering procedures in rheumatology: the use of animal models.

    NARCIS (Netherlands)

    Kraan, P.M. van der; Loo, F.A.J. van de; Berg, W.B. van den

    2004-01-01

    Tissue engineering is not only the application of cells and scaffolds to generate a new tissue but should also bring into play biological principles to guide cellular behavior. A way to modify cellular behavior is genetic modification of the cells used for tissue engineering (gene therapy). In the

  13. Engineering Nanomedicines to Overcome Multidrug Resistance in Cancer Therapy.

    Science.gov (United States)

    Beretta, Giovanni L; Cavalieri, Francesca

    2016-01-01

    Drug resistance to conventional antitumor drugs represents one of the major causes of treatment failure in patients affected by tumors. Two main types of drug resistance to anticancer drugs are found in tumors, namely intrinsic resistance, in which tumor cells are inherently resistant to chemotherapy, and acquired resistance, which results from previous drug exposure. Tumor cells resistant to a chemotherapeutic agent become cross-resistant to both similar and structurally unrelated classes of antitumor drugs, a biological mechanism known as multi drug resistance (MDR). Among the strategies considered to overcome MDR, nanovector-mediated drug administration represents an innovative and promising alternative. In this review, we report a number of nanovectors including polymer-drug conjugates, polymeric micelles, nanotubes, LbL nanocapsules, and silica and gold nanoparticles. These systems are designed for the efficient delivery of anthracyclines, vinca alkaloids, taxanes, and others drugs. The development of these nanovectos to specifically overcome MDR and their mechanisms of action are covered and discussed. Finally, we discuss challenges and opportunities for further development of nanodevices-based chemotherapies to circumvent MDR through the design of nanovectors for the delivery of multiple cargoes.

  14. Locoregional cancer therapy using polymer-based drug depots

    NARCIS (Netherlands)

    Ramazani, F.; van Nostrum, C.F.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria; Hennink, W.E.; Kok, R.J.

    2016-01-01

    Locoregional delivery of anticancer drugs is an attractive approach to minimize adverse effects associated with intravenous chemotherapy. Polymer-based drug depots injected or implanted intratumorally or adjacent to the tumor can provide long-term local drug exposure. This review highlights studies

  15. drug use evaluation on cotrimoxazole preventive therapy for people

    African Journals Online (AJOL)

    user

    BACKGROUND: Drug use evaluation is a performance improvement method that focuses on evaluation and improvement of drug use ... KEY WORDS: drug use evaluation, cotrimoxazole, HIV/AIDS, Jimma, Ethiopia. INTRODUCTION .... female was pregnant but the pregnancy history of 11. (35.5%) females was not ...

  16. [Comparing the effects of drug therapy, physical therapy, and exercise on pain, disability, and depression in patients with chronic low back pain].

    Science.gov (United States)

    Ko, Ja Kyung

    2007-08-01

    This research was conducted to compare the effects of drug therapy, physical therapy, and exercise on pain, disability, and depression in patients with chronic low back pain. The research design of this study was a nonequivalent control group pretest-posttest design. The subjects of this study were 28 patients for the drug therapy & physical therapy, 24 patients for the drug therapy & exercise, and 22 patients for the physical therapy & exercise. Data was collected by MVAS, Oswestry disability questionnaires, and questionnaires of depression. It was analyzed by paired t-test for effectiveness, ANOVA, and Scheffe for comparison of the effects of the 3 experimental treatments, using SPSS/WIN 12.0. There were no effects of drug therapy & physical therapy on pain, disability, and depression. However, there were effects of drug therapy & exercise and the physical therapy & exercise on pain, disability, and depression. The effects of physical therapy & exercise on pain, disability, and depression were the greatest, but there was no statistically significant differences between the drug therapy & exercise and the physical therapy & exercise. Exercise is regarded as a more effective and easily accessible nursing intervention to apply alone than drug therapy or physical therapy simultaneously in reducing pain, disability and depression.

  17. Light therapy: Methodological issues from an engineering perspective

    NARCIS (Netherlands)

    Westerlaken, A.C.; Hoof, J. van; Aarts, M.P.J.; Wouters, E.J.M.; Schoutens, A.M.C.; Sinoo, M.M.; Aries, M.B.C.

    2012-01-01

    Light therapy is increasingly administered and studied as a non-pharmacologic treatment for a variety of healthrelated problems, including treatment of people with dementia. Light therapy comes in a variety of ways, ranging from being exposed to daylight, to being exposed to light emitted by light

  18. Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-10-01

    Full Text Available Chitosan, a natural cationic polysaccharide, is prepared industrially by the hydrolysis of the aminoacetyl groups of chitin, a naturally available marine polymer. Chitosan is a non-toxic, biocompatible and biodegradable polymer and has attracted considerable interest in a wide range of biomedical and pharmaceutical applications including drug delivery, cosmetics, and tissue engineering. The primary hydroxyl and amine groups located on the backbone of chitosan are responsible for the reactivity of the polymer and also act as sites for chemical modification. However, chitosan has certain limitations for use in controlled drug delivery and tissue engineering. These limitations can be overcome by chemical modification. Thus, modified chitosan hydrogels have gained importance in current research on drug delivery and tissue engineering systems. This paper reviews the general properties of chitosan, various methods of modification, and applications of modified chitosan hydrogels.

  19. Engineering applications of nanotechnology from energy to drug delivery

    CERN Document Server

    Hamid, Nor

    2017-01-01

    This book focuses on the use of nanotechnology in several fields of engineering. Among others, the reader will find valuable information as to how nanotechnology can aid in extending the life of component materials exposed to corrosive atmospheres, in thermal fluid energy conversion processes, anti-reflection coatings on photovoltaic cells to yield enhanced output from solar cells, in connection with friction and wear reduction in automobiles, and buoyancy suppression in free convective heat transfer. Moreover, this unique resource presents the latest research on nanoscale transport phenomena and concludes with a look at likely future trends.

  20. What’s in a Name? Student Pharmacists’ Novel Extracurricular Process of Drug Therapy Reinforcement

    Directory of Open Access Journals (Sweden)

    Kenric B. Ware

    2017-05-01

    Full Text Available Fostering excitement in pharmacy student learning can be achieved through reinforcing drug therapies in curricular and extracurricular endeavors. This paper described an extracurricular initiative that elevated awareness of drug therapy in its current, future, and past members. This process occurred on an annual basis. Upon invitation, participants were expected to attend meetings with current and graduate organizational members. These settings provided opportunities for recognition and remembrance of organizational history and drug therapies. Checkpoints were inserted to verify progression towards full membership. The primary role of graduate members in this process was the yielding of their professional insights. A student – led, peer – facilitated model of drug therapy exposure along these lines resonates with calls for increased innovative learning strategies.

  1. Effects of aerobic exercise and drug therapy on blood pressure and ...

    African Journals Online (AJOL)

    EB

    Key words: Aerobic exercise, drug therapy, blood pressure, randomised controlled trial. African Health ... of home settings, and that could allow for supports in terms of family ... not and whether each number in a set should remain unique ...

  2. Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies.

    Science.gov (United States)

    Zumla, Alimuddin; Chakaya, Jeremiah; Centis, Rosella; D'Ambrosio, Lia; Mwaba, Peter; Bates, Matthew; Kapata, Nathan; Nyirenda, Thomas; Chanda, Duncan; Mfinanga, Sayoki; Hoelscher, Michael; Maeurer, Markus; Migliori, Giovanni Battista

    2015-03-01

    WHO estimates that 9 million people developed active tuberculosis in 2013 and 1·5 million people died from it. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis continue to spread worldwide with an estimated 480,000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis are still low and development of new, more effective tuberculosis drugs and adjunct therapies to improve treatment outcomes are urgently needed. Although standard therapy for drug-sensitive tuberculosis is highly effective, shorter, more effective treatment regimens are needed to reduce the burden of infectious cases. We review the latest WHO guidelines and global recommendations for treatment and management of drug-sensitive and drug-resistant tuberculosis, and provide an update on new drug development, results of several phase 2 and phase 3 tuberculosis treatment trials, and other emerging adjunct therapeutic options for MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and gatifloxacin) regimens have failed to shorten duration of therapy, and the new tuberculosis drug pipeline is sparse. Scale-up of existing interventions with increased investments into tuberculosis health services, development of new antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary political leadership, are still our best chance to change the unacceptable status quo of the tuberculosis situation worldwide and the growing problem of drug-resistant tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Polypathology, polypharmacy, medication regimen complexity and drug therapy appropriateness.

    Science.gov (United States)

    Gómez Aguirre, N; Caudevilla Martínez, A; Bellostas Muñoz, L; Crespo Avellana, M; Velilla Marco, J; Díez-Manglano, J

    Polypathological patients are usually elderly and take numerous drugs. Polypharmacy affects 85% of these individuals and is not associated with greater survival. On the contrary, polypharmacy exposes these individuals to more adverse effects, such as weight loss, falls, functional and cognitive impairment and hospitalisations. The complexity of a drug regimen covers more aspects than the simple number of drugs consumed. The galenic form, the dosage and the method for preparing the drug can impede the understanding of and compliance with prescriptions. Both polypharmacy and therapeutic complexity are associated with poorer adherence by patients. To prevent polypharmacy, reduce complexity and improve adherence, the appropriate use of drugs is needed. Proper prescribing consists of selecting drugs that have clear evidence for their use in the indication, which are appropriate for the patient's circumstances, are well tolerated and cost-effective and whose benefits outweigh the risks. To improve the drug prescription, periodic reviews of the drugs need to be conducted, especially when the patient changes doctor and during healthcare transitions. The Beers and STOPP/START (Screening Tool of Older Person's potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria are effective tools for this improvement. Deprescription for polymedicated polypathological patients that considers their clinical circumstances, prognosis and preferences can contribute to a more appropriate use of drugs. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  4. Feature Engineering for Recognizing Adverse Drug Reactions from Twitter Posts

    Directory of Open Access Journals (Sweden)

    Hong-Jie Dai

    2016-05-01

    Full Text Available Social media platforms are emerging digital communication channels that provide an easy way for common people to share their health and medication experiences online. With more people discussing their health information online publicly, social media platforms present a rich source of information for exploring adverse drug reactions (ADRs. ADRs are major public health problems that result in deaths and hospitalizations of millions of people. Unfortunately, not all ADRs are identified before a drug is made available in the market. In this study, an ADR event monitoring system is developed which can recognize ADR mentions from a tweet and classify its assertion. We explored several entity recognition features, feature conjunctions, and feature selection and analyzed their characteristics and impacts on the recognition of ADRs, which have never been studied previously. The results demonstrate that the entity recognition performance for ADR can achieve an F-score of 0.562 on the PSB Social Media Mining shared task dataset, which outperforms the partial-matching-based method by 0.122. After feature selection, the F-score can be further improved by 0.026. This novel technique of text mining utilizing shared online social media data will open an array of opportunities for researchers to explore various health related issues.

  5. Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

    Science.gov (United States)

    Labib, Gihan

    2018-01-01

    Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

  6. 3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

    Science.gov (United States)

    Goyanes, Alvaro; Wang, Jie; Buanz, Asma; Martínez-Pacheco, Ramón; Telford, Richard; Gaisford, Simon; Basit, Abdul W

    2015-11-02

    Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design

  7. Site-Specific Antibody–Drug Conjugates: The Nexus of Bioorthogonal Chemistry, Protein Engineering, and Drug Development

    Science.gov (United States)

    2015-01-01

    Antibody–drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering. PMID:25494884

  8. Mortality and Macrovascular Risk in Elderly with Hypertension and Diabetes: Effect of Intensive Drug Therapy.

    Science.gov (United States)

    Yashkin, Arseniy P; Kravchenko, Julia; Yashin, Anatoliy I; Sloan, Frank

    2017-08-14

    This study identifies the effect of intensive drug therapy in individuals age 65+ with diabetes (T2D) and hypertension on all-cause death, congestive heart failure (CHF) and hospitalization for myocardial infarction (MI) and stroke/transient ischemic attack (stroke/TIA). Individuals from the Medicare 5% dataset with hypertension and T2D undergoing intensive drug therapy for these conditions were propensity score matched to a non-intensive-drug-therapy group. Hazard ratios (HR) were obtained using the Cox proportional hazard model. Intensive drug therapy was associated with increased risk of CHF [HR: 2.32; 95% Confidence Interval (CI): 2.32-2.38], MI [HR: 4.27; CI: 4.05-4.52], and stroke/TIA [HR: 1.80; CI: 1.70-1.89] but decreased risk of death [HR: 0.95; CI: 0.93-0.97]. Risk for CHF [HR: 0.73; CI: 0.71-0.73], MI [HR: 0.64; CI: 0.62-0.67], stroke/TIA [HR: 0.82; CI: 0.78-0.86] and death [HR: 0.29; CI: 0.28-0.29] was decreased by adherence to diabetes management guidelines. Use of intensive drug therapy in a high-risk population delays death but not severe macrovascular outcomes. Protective effects of intensive drug therapy in high risk patients likely outweigh polypharmacy-related health concerns.

  9. Genome engineering: a new approach to gene therapy for neuromuscular disorders.

    Science.gov (United States)

    Nelson, Christopher E; Robinson-Hamm, Jacqueline N; Gersbach, Charles A

    2017-11-01

    For many neuromuscular disorders, including Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy, the genetic causes are well known. Gene therapy holds promise for the treatment of these monogenic neuromuscular diseases, and many such therapies have made substantial strides toward clinical translation. Recently, genome engineering tools, including targeted gene editing and gene regulation, have become available to correct the underlying genetic mutations that cause these diseases. In particular, meganucleases, zinc finger nucleases, TALENs, and the CRISPR-Cas9 system have been harnessed to make targeted and specific modifications to the genome. However, for most gene therapy applications, including genome engineering, gene delivery remains the primary hurdle to clinical translation. In preclinical models, genome engineering tools have been delivered via gene-modified cells or by non-viral or viral vectors to correct a diverse array of genetic diseases. In light of the positive results of these studies, genome engineering therapies are being enthusiastically explored for several genetic neuromuscular disorders. This Review summarizes the genome engineering strategies that are currently under preclinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on the molecular tools that show the greatest potential for clinical translation of these therapies.

  10. Improving the therapy of Cat II and drug resistant tuberculosis

    Indian Academy of Sciences (India)

    ... drug resistant tuberculosis. Improving methods for DST ( IRL and NRLs). Initiating DOTS plus treatment in selected centres. New drug regimens comprising of quinolones, ansamycins, clofazimine, PAS etc. Standard DOTS plus immunotherapy ( M.vaccae, Mw etc) : Eight centre multicentric trial of DOTS + Mw progressing.

  11. Development of Combination Therapy with Anti-Cancer Drugs

    NARCIS (Netherlands)

    Leijen, S.

    2013-01-01

    This thesis describes early clinical trials with anti-cancer drugs in combination with commonly applied and registered chemotherapy and single agent studies with compounds that are intended for use in combination with registered or other targeted anti-cancer drugs. Gemcitabine is a prodrug that

  12. Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

    Science.gov (United States)

    Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

    2017-09-01

    In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

  13. Family Therapy for Drug Abuse: Review and Updates 2003-2010

    Science.gov (United States)

    Rowe, Cynthia L.

    2012-01-01

    Just 15 years ago, Liddle and Dakof ("Journal of Marital and Family Therapy," 1995; 21, 511) concluded, based on the available evidence, that family therapy represented a "promising, but not definitive" approach for the treatment of drug problems among adolescents and adults. Seven years later, Rowe and Liddle (2003) review described considerable…

  14. Reasons for Change of Anti-Retroviral Therapy (ART) Drugs: Local ...

    African Journals Online (AJOL)

    Background: Highly active anti-retroviral therapy (HAART) reduces morbidity and mortality in HIV/AIDS infected patients. HAART is used indefinitely and the regimens are changed over the course of treatment due to resistance, adverse drug reactions or access to drugs. Few studies have been done in resource constrained ...

  15. Brief Strategic Family Therapy for Young People in Treatment for Drug Use

    Science.gov (United States)

    Lindstrøm, Maia; Filges, Trine; Jørgensen, Anne-Marie Klint

    2015-01-01

    Purpose: This review evaluates the evidence on the effects of brief strategic family therapy (BSFT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to prepare this review and ultimately located three studies for final analysis and interpretation. Results: The results…

  16. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Prescription drugs used in immunosuppressive... HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment...

  17. Functional Family Therapy for Young People in Treatment for Nonopioid Drug Use: A Systematic Review

    Science.gov (United States)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2018-01-01

    Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Results: The search yielded two…

  18. Cognitive-Behavioral Therapies for Young People in Outpatient Treatment for Nonopioid Drug Use

    Science.gov (United States)

    Filges, Trine; Jorgensen, Anne-Marie Klint

    2018-01-01

    Objectives: This review evaluates the evidence on the effects of cognitive-behavioral therapy (CBT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…

  19. Behavioral couples therapy (BCT) for alcohol and drug use disorders: A meta-analysis

    NARCIS (Netherlands)

    Powers, M.B.; Vedel, E.; Emmelkamp, P.M.G.

    2008-01-01

    Narrative reviews conclude that behavioral couples therapy (BCT) produces better outcomes than individual-based treatment for alcoholism and drug abuse problems (e.g., [Epstein, E. E., & McCrady, B. S. (1998). Behavioral couples treatment of alcohol and drug use disorders: Current status and

  20. Comparing immune-tumor growth models with drug therapy using optimal control

    Science.gov (United States)

    Martins, Marisa C.; Rocha, Ana Maria A. C.; Costa, M. Fernanda P.; Fernandes, Edite M. G. P.

    2016-06-01

    In this paper we compare the dynamics of three tumor growth models that include an immune system and a drug administration therapy using optimal control. The objective is to minimize a combined function of the total of tumor cells over time and a chemotherapeutic drug administration.

  1. Gene therapy in dentistry: tool of genetic engineering. Revisited.

    Science.gov (United States)

    Gupta, Khushboo; Singh, Saurabh; Garg, Kavita Nitish

    2015-03-01

    Advances in biotechnology have brought gene therapy to the forefront of medical research. The concept of transferring genes to tissues for clinical applications has been discussed nearly half a century, but the ability to manipulate genetic material via recombinant DNA technology has brought this goal to reality. The feasibility of gene transfer was first demonstrated using tumour viruses. This led to development of viral and nonviral methods for the genetic modification of somatic cells. Applications of gene therapy to dental and oral problems illustrate the potential impact of this technology on dentistry. Preclinical trial results regarding the same have been very promising. In this review we will discuss methods, vectors involved, clinical implication in dentistry and scientific issues associated with gene therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Drug delivery using composite scaffolds in the context of bone tissue engineering

    Science.gov (United States)

    Romagnoli, Cecilia; D’Asta, Federica; Brandi, Maria Luisa

    2013-01-01

    Summary Introduction Due to the disadvantages of the current bone autograft and allograft in many clinical condition in which bone regeneration is required in large quantity, engineered biomaterials combined with growth factors, such as bone morphogenetic protein-2 (BMP-2), have been demonstrated to be an effective approach in bone tissue engineering, since they can act both as a scaffold and as a drug delivery system to promote bone repair and regeneration. Area covered Recent advantages in the field of engineered scaffolds have been obtained from the investigation of composite scaffolds designed by the combination of bioceramics, especially hydroxyapatite (HA), and biodegradable polymers, such as poly (D,L-lactide-co-glycolide) (PLGA) and chitosan, in order to realize osteoconductive structures that can mimic the natural properties of bone tissue. Herein it is demonstrated that the incorporation of BMP-2 into different composite scaffolds, by encapsulation, absorption or entrapment, could be advantageous in terms of osteoinduction for new bone tissue engineered scaffolds as drug delivery systems and some of them should be further analyzed to optimized the drug release for future therapeutic applications. Expert opinion New design concepts and fabrication techniques represent novel challenges for further investigations about the development of scaffolds as a drug delivery system for bone tissue regeneration. PMID:24554923

  3. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering

    NARCIS (Netherlands)

    Stamatialis, Dimitrios; Papenburg, B.J.; Girones nogue, Miriam; Saiful, S.; Bettahalli Narasimha, M.S.; Schmitmeier, Stephanie; Wessling, Matthias

    2008-01-01

    This paper covers the main medical applications of artificial membranes. Specific attention is given to drug delivery systems, artificial organs and tissue engineering which seem to dominate the interest of the membrane community this period. In all cases, the materials, methods and the current

  4. Nanotechnology in drug delivery and tissue engineering: from discovery to applications.

    Science.gov (United States)

    Shi, Jinjun; Votruba, Alexander R; Farokhzad, Omid C; Langer, Robert

    2010-09-08

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine, drug delivery and tissue engineering, highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.

  5. Boosting immunity by antiviral drug therapy: A simple relationship among timing, efficacy, and success

    Science.gov (United States)

    Komarova, Natalia L.; Barnes, Eleanor; Klenerman, Paul; Wodarz, Dominik

    2003-02-01

    Drug therapies against persistent human infections such as hepatitis C virus, hepatitis B virus, and HIV fail to consistently eradicate the infection from the host. Hence, recent emphasis has shifted to the study of antiviral therapy aimed at boosting specific immune responses. It was argued that structured therapy interruptions were required to achieve this, because such regimes have shown promising results in early HIV infection. Using mathematical models, we show that, contrary to this notion, a single phase of drug therapy can result in the establishment of sustained immunity. We present a simple relationship between timing of therapy and efficacy of the drugs required for success. In the presence of strong viral suppression, we show that therapy should be stopped relatively early, and that a longer duration of treatment leads to failure. On the other hand, in the presence of weaker viral suppression, stopping treatment too early is detrimental, and therapy has to be continued beyond a time threshold. We discuss our modeling results primarily in the context of HCV therapy during chronic infection. Although the therapy regimes explored here also have implications for HIV, virus-mediated destruction of specific immune cells renders success unlikely during the chronic phase of the infection.

  6. Assessment of drug therapy in Parkinson’s disease

    OpenAIRE

    Arbouw, M.E.L.

    2010-01-01

    The pharmacological management of motor and non-motor symptoms of Parkinson’s disease (PD) is the central theme of this thesis. In a literature study, we revealed that relatively few efforts have been made to investigate the role of pharmacogenetics in the response to anti-PD drugs and that only few replication studies have been performed. Some interesting associations between genetic variants and anti-PD drug response have been found, but these were conflicting. We concluded that pharmacogen...

  7. An outline of main factors of drug resistance influencing cancer therapy.

    Science.gov (United States)

    Frączek, Natalia; Bronisz, Iwona; Pietryka, Magdalena; Kępińska, Dorota; Strzała, Patrycja; Mielnicka, Kamila; Korga, Agnieszka; Dudka, Jaroslaw

    2016-12-01

    Drug resistance in cancer therapy is a multifactorial phenomenon that determines remission or progression. It is known that resistance to used anticancer drugs may be the consequence of drug transport to the cell or intracellular distribution. It may also be the result of its molecular target structural change, apoptosis inhibition or increase in some enzymes activity, e.g. pentose phosphate pathway enzymes. Intrinsic (pre-existed) drug resistance is related to the phenotype of cancer as well as normal cells. Acquired, after partial administration of chemotherapy, type of drug resistance in addition to the starting phenotype is closely linked to the development of new more aggressive clones and adaptive processes. In both, the intrinsic and acquired resistance, role play also mutations. These may be partially spontaneous, but in terms of acquired resistance, they are mostly induced by the exposure to the drugs. The article mentions some traditional mechanisms related to the acquisition of resistance by cancer cells during therapy, through the protein transporters, apoptosis deregulation, angiogenesis and the impact of the tumour microenvironment. We focused however on some more alternative ways of therapy resistance, such as, hypoxia and tumour acidification, cancer stem cells (CSCs), exosomes and radiotherapy resistance. A concise summary of the drug resistance presented in the paper may be an important aspect in studies to increase the effectiveness of cancer therapies.

  8. Genetic correction using engineered nucleases for gene therapy applications.

    Science.gov (United States)

    Li, Hongmei Lisa; Nakano, Takao; Hotta, Akitsu

    2014-01-01

    Genetic mutations in humans are associated with congenital disorders and phenotypic traits. Gene therapy holds the promise to cure such genetic disorders, although it has suffered from several technical limitations for decades. Recent progress in gene editing technology using tailor-made nucleases, such as meganucleases (MNs), zinc finger nucleases (ZFNs), TAL effector nucleases (TALENs) and, more recently, CRISPR/Cas9, has significantly broadened our ability to precisely modify target sites in the human genome. In this review, we summarize recent progress in gene correction approaches of the human genome, with a particular emphasis on the clinical applications of gene therapy. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  9. Stem cell therapy and tissue engineering for correction of congenital heart disease

    OpenAIRE

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is...

  10. Genetically Engineered Autologous Cells for Antiangiogenic Therapy of Breast Cancer

    Science.gov (United States)

    2004-07-01

    Thus, diseases such as cancer, hemophilia , growth or other hormone deficiency. and all diseases 7 amenable to therapeutic plasma protein delivery...were washed and acquired using a FACS Calibur flow cytometer (BD Immunocytometry systems) and analyzed with Cellquest software. Marrow Stroma...Pharm. 221: 1-22. 17. Lu, D.R., et al. (1993). Stage I clinical trial of gene therapy for hemophilia B. Science in China - Series B, Chemistry, Life

  11. Various pharmacogenetic aspects of antiepileptic drug therapy: a review.

    Science.gov (United States)

    Mann, Michael W; Pons, Gerard

    2007-01-01

    Pharmacogenetics concerns the influence of an individual's genetic background on the pharmacokinetics and pharmacodynamics of xenobiotics. Much of the pharmacogenetic data in the field of epilepsy deals with the pharmacokinetics of antiepileptic drugs (AEDs). In particular, two polymorphisms of cytochrome P450 2C9 are known to slow down the metabolism of phenytoin to a degree that increases the risk of the neurotoxic adverse effects of this drug among carriers of these polymorphisms. A significant number of patients with epilepsy do not respond to AEDs and such pharmacoresistance is a major, largely unsolved, problem that is likely to be multifactorial in nature. In this regard, genetic factors may influence transmembrane drug transporter proteins, thereby modifying the intracerebral penetration of AEDs. Monogenic idiopathic epilepsies are rare and frequently associated with ion channel mutations; however, to date, a consistent relationship between changes in channel properties and clinical phenotype has not been established nor has any association between genotype and response to specific treatment options. Polymorphisms of drug targets may represent another genetic facet in epilepsy: a recent study demonstrated for the first time a polymorphism of a drug target (the alpha-subunit of a voltage-gated sodium channel) associated in clinical practice with differing response to two classic AEDs. Adverse drug reactions and teratogenicity of AEDs remain a major concern. Whole-genome single nucleotide polymorphism profiling might in the future help to determine genetic predisposing factors for adverse drug reactions. Recently, in Han Chinese treated with carbamazepine and presenting with Stevens-Johnson syndrome, a strong association was found with HLA B*1502. If genetically targeted drug development becomes more affordable/cost efficient in the near future, the development of new drugs for relatively rare diseases could become economically viable for the pharmaceutical

  12. Intravenous lipids: antidotal therapy for drug overdose and toxic effects of local anesthetics.

    Science.gov (United States)

    Bartlett, Dana

    2014-10-01

    Intravenous lipid emulsion is an accepted therapy for the treatment of severe cardiac toxic effects caused by local anesthetics. Lipid emulsion therapy has also been used successfully to treat cardiac arrest and intractable arrhythmias caused by overdoses of antiepileptic drugs, cardiovascular drugs, and psychotropic medications, but experience with intravenous lipids as antidotal therapy in these clinical situations is limited. However, intravenous lipids are relatively safe, widely available, and easy to administer, and many published case reports document their dramatic effectiveness. Patients who have not responded to standard therapies have been quickly revived by administration of intravenous lipids. Use of lipids most likely will increase, and critical care nurses should be familiar with lipid therapy. ©2014 American Association of Critical-Care Nurses.

  13. Clinical and economic outcomes of pharmacist-managed antiepileptic drug therapy.

    Science.gov (United States)

    Bond, C A; Raehl, Cynthia L

    2006-10-01

    This study explores the associations between pharmacist-managed antiepileptic drug therapy in hospitalized Medicare patients and diagnoses indicating the need for these drugs. It also explores the following major heath care outcomes: death rate, hospital length of stay (LOS), Medicare charges, drug charges, laboratory charges, complications, and adverse drug reactions. Data were drawn from the 1998 MedPAR and 1998 National Clinical Pharmacy Services databases. Pharmacist-managed antiepileptic drug therapy was evaluated in a study population of 9380 Medicare patients with diagnosed epilepsy or seizure disorders treated in 794 United States hospitals. This population was derived from the 38,311 hospitalized Medicare patients with epilepsy or seizure disorders (MedPAR). In hospitals without pharmacist-managed antiepileptic drug therapy, death rates were 120.61% higher, with 374 excess deaths (chi(2)=5.983, df=1, p=0.014, odds ratio [OR]=1.553, 95% confidence interval [CI] 1.102-2.189). Hospital LOS was 14.68% higher, with 8069 patient-days (Mann-Whitney U test [U]=3833132, p=0.0009); total Medicare charges were 11.19% higher, with 14,372,550 dollars in excess total charges (U=3644199, p=0.0003); per-patient drug charges were $115 +/- $92 higher (p=NS); laboratory charges were 32.24% higher, with 5,664,970 dollars in excess charges; and aspiration pneumonia rate was 54.61% higher (chi(2)=5.848, df=1, p=0.015, OR=1.233, 95% CI 1.081-1.901). Although the frequencies of other complications and adverse effects were higher, these differences were not statistically significant compared with hospitals with pharmacist-managed antiepileptic drug therapy. Clinical and economic outcomes were improved among hospitalized Medicare patients whose antiepileptic drug therapy was managed by pharmacists.

  14. Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy.

    Science.gov (United States)

    Hsu, Kuan-Hui; Carbia, Blanca E; Plummer, Caryn; Chauhan, Anuj

    2015-08-01

    Glaucoma patients frequently instill eye drops multiple times each day, which is a cause for reduced compliance. Additionally, eye drops suffer from other limitations including low bioavailability, which can lead to side effects. We propose to develop drug-eluting contact lenses for managing glaucoma with increased bioavailability and improved compliance. Contact lenses are developed for extended simultaneous release of timolol and dorzolamide, both of which are commonly prescribed hydrophilic drugs. The extended release is achieved by loading lenses with vitamin E barriers. In vitro release studies are performed with control and vitamin E loaded lenses for both drugs loaded separately and then together in the same lens. The safety and efficacy of combination therapy by contacts are demonstrated in a Beagle model of glaucoma. Simultaneous loading of timolol and dorzolamide increases the release duration of both drugs. Also vitamin E incorporation is highly effective in increasing the release durations of both drugs to about 2-days. The lenses loaded with both drugs exhibited superior IOP reduction compared to eye drops with about 6-fold lower drug loading. More importantly, combination therapy by continuous wear of vitamin E loaded contact for 2-days, followed by a new set of contacts for another two days, reduced IOP during the 4days of wear time and for another 8days after removal of the contacts. Vitamin E loading is very effective for providing combination therapy by contact lenses due to the increase in release durations of several drugs. The contact lens based therapy reduces IOP with lower drug dose compared to eye drops and may significantly improve the compliance as the effect of the therapy lasts significantly longer than the wear-duration. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Access to antiepileptic drug therapy in children in Camagüey Province, Cuba

    Science.gov (United States)

    Arencibia, Zeina Bárzaga; Leyva, Alberto López; Peña, Yordanka Mejías; Reyes, Alba Rosa González; Nápolez, Maurilys Acosta; Carbonell Perdomo, Demetrio; Manzano, Edita Fernández; Choonara, Imti

    2012-01-01

    Objective To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba. Methods All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs. Results There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower-middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine. Conclusions The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower-middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower-middle income countries. PMID:23134098

  16. Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities

    Directory of Open Access Journals (Sweden)

    Carlos Brites

    2016-07-01

    Conclusions: The resistance mutational profile of Brazilian patients failing antiretroviral therapy is quite variable, depending on the city where patients were tested. This variation likely reflects distinctive choice of antiretrovirals drugs to initiate therapy, adherence to specific drugs, or circulating HIV-1 strains. Overall, etravirine and DRV/r remain as the most active drugs.

  17. Colon cancer therapy: recent developments in nanomedicine to improve the efficacy of conventional chemotherapeutic drugs.

    Science.gov (United States)

    Prados, J; Melguizo, C; Ortiz, R; Perazzoli, G; Cabeza, L; Alvarez, P J; Rodriguez-Serrano, F; Aranega, A

    2013-10-01

    The number of patients with colorectal cancer, the third most frequently diagnosed malignancy in the world, has increased markedly over the past 20 years and will continue to increase in the future. Despite recent advances in chemotherapy, currently used anticancer molecules are unable to improve the prognosis of advanced or recurrent colorectal cancer, which remains incurable. The transport of classical drugs by nanoparticles has shown great promise in terms of improving drug distribution and bioavailability, increasing tissue half-life and concentrating anticancer molecules in the tumor mass, providing optimal drug delivery to tumor tissue, and minimizing drug toxicity, including those effects associated with pharmaceutical excipients. In addition, colon cancer targeting may be improved by incorporating ligands for tumor-specific surface receptors. Similarly, nanoparticles may interact with key drug-resistance molecules to prevent a reduction in intracellular drug levels drug. Recently published data have provided convincing pre-clinical evidence regarding the potential of active-targeted nanotherapeutics in colon cancer therapy, although, unfortunately, only a few of these therapies have been translated into early-phase clinical trials. As nanotechnology promises to be a new strategy for improving the prognosis of colon cancer patients, it would be very useful to analyze recent progress in this field of research. This review discusses the current status of nanoparticle-mediated cancer-drug delivery, the challenges restricting its application, and the potential implications of its use in colon cancer therapy.

  18. Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.

    Science.gov (United States)

    Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar

    2012-09-01

    Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Engineered reversal of drug resistance in cancer cells--metastases suppressor factors as change agents.

    Science.gov (United States)

    Yadav, Vinod Kumar; Kumar, Akinchan; Mann, Anita; Aggarwal, Suruchi; Kumar, Maneesh; Roy, Sumitabho Deb; Pore, Subrata Kumar; Banerjee, Rajkumar; Mahesh Kumar, Jerald; Thakur, Ram Krishna; Chowdhury, Shantanu

    2014-01-01

    Building molecular correlates of drug resistance in cancer and exploiting them for therapeutic intervention remains a pressing clinical need. To identify factors that impact drug resistance herein we built a model that couples inherent cell-based response toward drugs with transcriptomes of resistant/sensitive cells. To test this model, we focused on a group of genes called metastasis suppressor genes (MSGs) that influence aggressiveness and metastatic potential of cancers. Interestingly, modeling of 84 000 drug response transcriptome combinations predicted multiple MSGs to be associated with resistance of different cell types and drugs. As a case study, on inducing MSG levels in a drug resistant breast cancer line resistance to anticancer drugs caerulomycin, camptothecin and topotecan decreased by more than 50-60%, in both culture conditions and also in tumors generated in mice, in contrast to control un-induced cells. To our knowledge, this is the first demonstration of engineered reversal of drug resistance in cancer cells based on a model that exploits inherent cellular response profiles.

  20. Production of orally applicable new drug or drug combinations from natural origin capsaicinoids for human medical therapy.

    Science.gov (United States)

    Mózsik, Gyula; Past, Tibor; Dömötör, András; Kuzma, Mónika; Perjési, Pál

    2010-01-01

    It is well known that the capsaicin stimulates (in small doses) or impairs (in high doses) the capsaicin-sensitive afferent nerves and the final effects of capsaicin depend on its applied doses. The effects of capsaicin were analyzed on the gastrointestinal mucosal protection and injury in animal experiments and in human beings (from 1980 up to now). From 2005 to 2008 an interdisciplinary group (21 researchers) participated in the production of orally applicable drug or drug combinations from capsaicin for human medical therapy of patients suffering from cardiovascular, degenerative joint and locomotor diseases, who received in their treatments non-steroidal anti-inflammatory compounds (NSAIDs). Our studies were based on the results of the NSAIDs-induced gastrointestinal side effects could be detected by application of small doses of capsaicin. Because natural (plant origin) capsaicin is chemically does not represent a uniform entity and used in the international research, consequently the authors met a lot of unpredictable scientific problems during the time of production of new capsaicin containing (alone or in combinations) drug before receiving official permissions from the different national and international authorities to start the classical human clinical pharmacological studies. This paper summarizes the different steps from the basic physiological and pharmacological notes (in animals), plant cultivation, chemistry of substance(s), animal (general and germinative) acute and chronic toxicology, human actions, basic clinical pharmacology of natural capsaicin (capsaicinoids) to introduce and to develop a new drug (or drug combinations) in the human medical therapy.

  1. A Drug Discovery Partnership for Personalized Breast Cancer Therapy

    Science.gov (United States)

    2014-09-01

    Bhattacharjee , Biology Department, “Peptidomimetic therapy of angiogenesis” 8- Monday December 2, 2013, Dr. Hector Biliran, Biology Department, “TLE1...Karen Zhang, Computer Science Department 22- Monday April 28, 2014, Dr. Partha Bhattacharjee , Biology Department In addition, the researchers on each

  2. Anaesthesia for electroconvulsive therapy - new tricks for old drugs

    DEFF Research Database (Denmark)

    Stripp, Tobias Kvist; Jorgensen, Martin Balslev; Olsen, Niels Vidiendal

    2018-01-01

    OBJECTIVE: The objective of this review is to investigate existing literature in order to delineate whether the use of anaesthesia and timing of seizure induction in a new and optimised way may improve the efficacy of electroconvulsive therapy (ECT). METHODS: PubMed/MEDLINE was searched for exist...

  3. Amiodarone therapy for drug-refractory fetal tachycardia

    NARCIS (Netherlands)

    Strasburger, JF; Cuneo, BF; Michon, MM; Gotteiner, NL; Deal, BJ; McGregor, SN; Oudijk, MA; Meijboom, EJ; Feinkind, L; Hussey, M; Parilla, BV

    2004-01-01

    Background - Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This

  4. Combination Drug Therapy for Benign Prostatic Hyperplasia (BPH ...

    African Journals Online (AJOL)

    BPH symptom reduction and shrinkage of prostate size by the use of a combination of alpha adrenergic uroselective blocker (Tamsulosin) and 5 alpha iso-enzyme inhibitor (Dutasteride) is a first option of therapy in the management of BPH especially in those cases that are surgical risks with the category of mild to moderate ...

  5. Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery.

    Science.gov (United States)

    Patil, Sharvil; Mahadik, Abhijeet; Nalawade, Pradeep; More, Priyesh

    2017-12-01

    Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr's index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose(®) (SV003, Goch, Germany)] used in DPI formulations. EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose(®) (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose(®) (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.

  6. Role of disease-modifying antirheumatic drugs versus cytotoxic agents in the therapy of rheumatoid arthritis.

    Science.gov (United States)

    Ward, J R

    1988-10-14

    Disease-modifying antirheumatic drugs are used to modify or alter the rheumatoid arthritis disease process. Disease-modifying antirheumatic drugs do not demonstrate the characteristic analgesic, antipyretic, and anti-inflammatory actions of the nonsteroidal anti-inflammatory drugs, since weeks or months of treatment are required before clinical benefit is observed. Although they have not been proved to delay, prevent, or reverse articular damage, therapy with disease-modifying antirheumatic drugs, when successful, is associated with decreased pain and joint swelling and improved function. Disease-modifying antirheumatic drugs and cytotoxic agents should not be considered as routine treatment for patients with rheumatoid arthritis. Before disease-modifying antirheumatic drug therapy is implemented, an optimal basic program of physical therapy, rest, and nonsteroidal anti-inflammatory drugs should be implemented, and it must be documented that the patient still has sufficient disease to justify the costs, risks, and benefits of these treatments. Drugs that are approved by the Food and Drug Administration (FDA) are preferred over nonapproved drugs. Hydroxychloroquine, parenteral gold salts, oral gold, D-penicillamine, and the cytotoxic drug azathioprine are the FDA-approved disease-modifying antirheumatic drugs for use in rheumatoid arthritis. Many, not all, rheumatologists would employ hydroxychloroquine as the first-choice disease-modifying antirheumatic drug in patients who have early, mild, and nonerosive disease; treatment should be continued for six months before being abandoned for lack of efficacy, and appropriate ophthalmologic examination every four to six months is indicated. An alternative would be auranofin, whose efficacy approaches that of parenteral gold, yet may be safer. For patients who have severe active rheumatoid arthritis, especially with erosive changes, parenteral gold salts are usually a first choice. D-penicillamine is also effective in

  7. Adverse drug reactions associated with antiretroviral therapy in ...

    African Journals Online (AJOL)

    ... prone to experience gynaecomastia and peripheral neuropathy. In addition, patients aged 30–44 years reported the most ADRs. Most reactions resulted from the use of stavudine, efavirenz, zidovudine, nevirapine and tenofovir in the population groups identified in this study. Keywords: pharmacovigilance, drug safety, ...

  8. Clinically relevant pharmacokinetic herb-drug interactions in antiretroviral therapy

    Science.gov (United States)

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In t...

  9. A Drug Discovery Partnership for Personalized Breast Cancer Therapy

    Science.gov (United States)

    2015-09-01

    for each compound. 2D NMR spectra clarify the stereochemistry of compounds. Through molecular simulation and conformational analysis , dual...1A2-targeting cancer preventive agents. Wiese/Burow Subproject (Identification of novel estrogens and antiestrogens in the USDA Phytochemical and...antagonists) and then virtually screen the USDA Phytochemical , Chinese Herbal Medicine, and the FDA Marketed Drug Databases for new estrogens. Task 1

  10. Assessment of drug therapy in Parkinson’s disease

    NARCIS (Netherlands)

    Arbouw, M.E.L.

    2010-01-01

    The pharmacological management of motor and non-motor symptoms of Parkinson’s disease (PD) is the central theme of this thesis. In a literature study, we revealed that relatively few efforts have been made to investigate the role of pharmacogenetics in the response to anti-PD drugs and that only few

  11. Drug treatment of obesity: established and emerging therapies.

    Science.gov (United States)

    Isidro, M Luisa; Cordido, Fernando

    2009-06-01

    Available anti-obesity pharmacotherapy options remain very limited. The development of more effective drugs has become a priority. The potential strategies to achieve weight loss are to reduce energy intake, by stimulating anorexigenic signals or by blocking orexigenic signals, and to increase energy expenditure. This review will focus on approved obesity medications, as well as potential new pharmacological treatment options.

  12. Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures

    OpenAIRE

    Haeseung Lee; Seungmin Kang; Wankyu Kim

    2016-01-01

    An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug's mode-of-action. First, the drug-induced expression profile...

  13. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-01-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

  14. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-06-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

  15. Drug-Induced Self-Assembly of Modified Albumins as Nano-theranostics for Tumor-Targeted Combination Therapy.

    Science.gov (United States)

    Chen, Qian; Wang, Xin; Wang, Chao; Feng, Liangzhu; Li, Yonggang; Liu, Zhuang

    2015-05-26

    Paclitaxel (PTX) can bind to human serum albumin (HSA) via hydrophobic interaction, forming Abraxane, which is a U.S. Food and Drug Administration (FDA) approved effective antitumor nanomedicine drug. Herein, the effective antitumor drug PTX is used to induce the self-assembly of HSA modified with either a photosensitizer chlorin e6 (Ce6), which at the same time serves as a chelating agent for Mn(2+) to enable magnetic resonance imaging, or acyclic Arg-Gly-Asp (cRGDyK) peptide that targets αvβ3-integrin overexpressed on tumor angiogenic endothelium. Two types of tumor-targeting theranostic nanoparticles are constructed, either by coassembly of both HSA-Ce6 and HSA-RGD simultaneously or by forming an HSA-Ce6@HSA-RGD core-shell structure, with the assistance of PTX-induced albumin aggregation. Such albumin-based nanoparticles on one hand could targetαvβ3-integrin, as evidenced by both in vitro and in vivo experiments, and on the other hand enable combined photodynamic/chemotherapy, which offers remarkably improved therapeutic efficacy to kill cancer in comparison to the respective monotherapies. Our work presents a new type of tumor-targeted multifunctional albumin-based nanoparticles by drug-induced self-assembly, which is a rather simple method without any sophisticated chemistry or materials engineering and is promising for multimodel imaging-guided combination therapy of cancer.

  16. Magnetic Nanomaterials for Hyperthermia-based Therapy and Controlled Drug Delivery

    Science.gov (United States)

    Kumar, Challa S. S. R.; Mohammad, Faruq

    2011-01-01

    Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “Hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled Drug delivery through Bond Breaking (DBB) and Hyperthermia-based controlled Drug delivery through Enhanced Permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities in the combination of hyperthermia-based therapy and controlled drug release paradigms for successful application in personalized medicine. PMID:21447363

  17. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery.

    Science.gov (United States)

    Kumar, Challa S S R; Mohammad, Faruq

    2011-08-14

    Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term "hyperthermia" in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term "hyperthermia" by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled drug delivery through bond breaking (DBB) and hyperthermia-based controlled drug delivery through enhanced permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities for the combination of hyperthermia-based therapy and controlled drug release paradigms--towards successful application in personalized medicine. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. How could preventive therapy affect the prevalence of drug resistance? Causes and consequences.

    Science.gov (United States)

    Kunkel, Amber; Colijn, Caroline; Lipsitch, Marc; Cohen, Ted

    2015-06-05

    Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects.

  19. Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

    Energy Technology Data Exchange (ETDEWEB)

    Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar, E-mail: swatantrakushwaha@yahoo.co.in [Pranveer Singh Institute of Technology, Kanpur (India); Singh, Satyawan [Saroj Institute of Technology and Management, Lucknow (India)

    2013-10-15

    Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

  20. Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

    Directory of Open Access Journals (Sweden)

    Swatantra Kumar Singh Kushwaha

    2013-12-01

    Full Text Available Carbon nanotubes (CNTs were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field.

  1. The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering.

    Science.gov (United States)

    Kim, Sally Yunsun; Wong, Alice Hai May; Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Chan, Hak-Kim

    2015-06-01

    Search for new, functional biomaterials that can be used to synergistically deliver a drug, enhance its adsorption and stimulate the post-injury recovery of tissue function, is one of the priorities in biomedicine. Currently used materials for drug delivery fail to satisfy one or more of these functionalities, thus they have limited potential and new classes of materials are urgently needed. Natural materials, due to their origin, physical and chemical structure can potentially fulfill these requirements and there is already strong evidence of their usefulness in drug delivery. They are increasingly utilized in various therapeutic applications due to the obvious advantages over synthetic materials. Particularly in pulmonary drug delivery, there have been limitations in the use of synthetic materials such as polymers and lipids, leading to an increase in the use of natural and protein-based materials such as silk, keratin, elastin and collagen. Literature search in each specialized field, namely, silk, keratin and collagen was conducted, and the benefits of each material for future application in pulmonary drug delivery are highlighted. The natural materials discussed in this review have been well established in their use for other applications, yet further studies are required in the application of pulmonary drug delivery. The properties exhibited by these natural materials seem positive for their application in lung tissue engineering, which may allow for more extensive testing for validation of pulmonary drug delivery systems.

  2. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    Science.gov (United States)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  3. An update on applications of nanostructured drug delivery systems in cancer therapy: a review.

    Science.gov (United States)

    Aberoumandi, Seyed Mohsen; Mohammadhosseini, Majid; Abasi, Elham; Saghati, Sepideh; Nikzamir, Nasrin; Akbarzadeh, Abolfazl; Panahi, Yunes; Davaran, Soodabeh

    2017-09-01

    Cancer is a main public health problem that is known as a malignant tumor and out-of-control cell growth, with the potential to assault or spread to other parts of the body. Recently, remarkable efforts have been devoted to develop nanotechnology to improve the delivery of anticancer drug to tumor tissue as minimizing its distribution and toxicity in healthy tissue. Nanotechnology has been extensively used in the advance of new strategies for drug delivery and cancer therapy. Compared to customary drug delivery systems, nano-based drug delivery method has greater potential in different areas, like multiple targeting functionalization, in vivo imaging, extended circulation time, systemic control release, and combined drug delivery. Nanofibers are used for different medical applications such as drug delivery systems.

  4. Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for Non-Opioid Drug Use:

    DEFF Research Database (Denmark)

    Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken

    2015-01-01

    BACKGROUND Youth drug use is a severe problem worldwide. This review focuses on Cognitive-Behavioural Therapy (CBT) as a treatment for young people who misuse non-opioid drugs, such as cannabis, amphetamines, ecstasy and cocaine, which are strongly associated with a range of health and social...... problems. CBT is an individualized and multicomponent intervention that combines behavioural and cognitive therapy. While behavioural therapy mainly focuses on external settings and observable behaviour, cognitive therapy is concerned with internal cognitive processes. The primary focus of CBT is to reduce...... literature databases, citations in other reviews and in the included primary studies, hand searches of relevant journals, and Internet searches using Google. We also corresponded with researchers in the CBT field. No language or date restrictions were applied to the searches. SELECTION CRITERIA Studies were...

  5. Versatile surface engineering of porous nanomaterials with bioinspired polyphenol coatings for targeted and controlled drug delivery

    Science.gov (United States)

    Li, Juan; Wu, Shuxian; Wu, Cuichen; Qiu, Liping; Zhu, Guizhi; Cui, Cheng; Liu, Yuan; Hou, Weijia; Wang, Yanyue; Zhang, Liqin; Teng, I.-Ting; Yang, Huang-Hao; Tan, Weihong

    2016-04-01

    The development of biocompatible drug delivery systems with targeted recognition and controlled release has experienced a number of design challenges, including, for example, complicated preparation steps and premature drug release. Herein, we address these problems through an in situ self-polymerization method that synthesizes biodegradable polyphenol-coated porous nanomaterials for targeted and controlled drug delivery. As a proof of concept, we synthesized polyphenol-coated mesoporous silica nanoparticles, termed MSN@polyphenol. The polyphenol coatings not only improved colloidal stability and prevented premature drug leakage, but also provided a scaffold for immobilization of targeting moieties, such as aptamers. Both immobilization of targeting aptamers and synthesis of polyphenol coating are easily accomplished without the aid of any other organic reagents. Importantly, the polyphenol coating (EGCg) used in this study could be biodegraded by acidic pH and intracellular glutathione, resulting in the release of trapped anticancer drugs. Based on confocal fluorescence microscopy and cytotoxicity experiments, drug-loaded and polyphenol-coated MSNs were shown to possess highly efficient internalization and an apparent cytotoxic effect on target cancer, but not control, cells. Our results suggest that these highly biocompatible and biodegradable polyphenol-coated MSNs are promising vectors for controlled-release biomedical applications and cancer therapy.The development of biocompatible drug delivery systems with targeted recognition and controlled release has experienced a number of design challenges, including, for example, complicated preparation steps and premature drug release. Herein, we address these problems through an in situ self-polymerization method that synthesizes biodegradable polyphenol-coated porous nanomaterials for targeted and controlled drug delivery. As a proof of concept, we synthesized polyphenol-coated mesoporous silica nanoparticles

  6. Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2015-11-01

    Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

  7. Drug-loaded biodegradable microspheres for image-guided combinatory epigenetic therapy in cells

    Science.gov (United States)

    Xu, Ronald X.; Xu, Jeff S.; Zuo, Tao; Shen, Rulong; Huang, Tim H.; Tweedle, Michael F.

    2011-02-01

    We synthesize drug-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for image-guided combinatory epigenetic therapy in MCF-10A human mammary epithelial cells. LY294002 and Nile Red are encapsulated in microspheres for sustained drug release and fluorescence microscopic imaging. Drug-loaded microspheres target MCF-10A cells through a three-step binding process involving biotinylated antibody, streptavidin, and biotinylated microspheres. LY294002 loaded microspheres and 5-Aza-2-deoxycytidine are applied to MCF-10A cells for combinatory PI3K/AKT inhibition and deoxyribonucleic acid (DNA) demethylation. Our study implies the technical potential of disease targeting and image-guided combinatory epigenetic therapy using drug-loaded multifunctional biodegradable PLGA microspheres.

  8. Family Behavior Therapy (FBT) for young people in treatment for non-opioid drug use:

    DEFF Research Database (Denmark)

    Lindstrøm, Maia; Saidj, Madina; Kowalski, Krystyna

    2015-01-01

    BACKGROUND Youth drug use is a severe problem worldwide, and the use of cannabis, amphetamine ecstasy and cocaine, referred to as non-opioid drugs, are strongly associated with a range of health and social problems. This review focuses on Family Behavior Therapy (FBT) as a treatment for young...... people who misuse non-opioid drugs. FBT is a manual-based family therapy approach. The program is behavior and skill-oriented. It is concerned with identifying psychological and situational stimuli and triggers presumed to be directly related to the youth’s drug use, and skills training to improve self...... language nor date restrictions were applied to the searches. SELECTION CRITERIA Studies eligible for inclusion in the review are required to meet several eligibility criteria. Studies must: • have involved a manual-based FBT treatment for young people aged 11-21 years enrolled in outpatient treatment...

  9. pH-sensitive nano-systems for drug delivery in cancer therapy.

    Science.gov (United States)

    Liu, Juan; Huang, Yuran; Kumar, Anil; Tan, Aaron; Jin, Shubin; Mozhi, Anbu; Liang, Xing-Jie

    2014-01-01

    Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nano-based drug delivery system have greater potential in a variety of areas, such as multiple targeting functionalization, in vivo imaging, combined drug delivery, extended circulation time, and systemic control release. Nano-systems incorporating stimulus-responsive materials have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. As a result of the active metabolism of tumor cells, the tumor microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive nano-systems have now been developed in which drug release is specifically triggered by the acidic tumor environment. Studies have demonstrated that novel pH-sensitive drug delivery systems are capable of improving the efficiency of cancer treatment. A number of these have been translated from bench to clinical application and have been approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. Herein, this review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field. With deeper understanding of the difference between normal and tumor tissues, it might be possible to design ever more promising pH-responsive nano-systems for drug delivery and cancer therapy in the near future. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  10. Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

    Directory of Open Access Journals (Sweden)

    Jiming Chen

    2008-03-01

    Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

  11. Is Resistance to Dolutegravir Possible When This Drug Is Used in First-Line Therapy?

    Directory of Open Access Journals (Sweden)

    Thibault Mesplède

    2014-08-01

    Full Text Available Dolutegravir (DTG is an HIV integrase inhibitor that was recently approved for therapy by the Food and Drug Administration in the United States. When used as part of first-line therapy, DTG is the only HIV drug that has not selected for resistance mutations in the clinic. We believe that this is due to the long binding time of DTG to the integrase enzyme as well as greatly diminished replication capacity on the part of viruses that might become resistant to DTG. We further speculate that DTG might be able to be used in strategies aimed at HIV eradication.

  12. Elsinochrome A photosensitizers: Alternative drugs for photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Tinghui Li

    2015-01-01

    Full Text Available Photodynamic therapy (PDT has already been a multifunctional modality for various tumors and nontumorous diseases. However, the development of photosensitizers is relatively delayed, compared with the tremendous progress in laser technology. Elsinochrome A (EA, a perylenequinonoid pigment from China, has all the typical advantages of perylenequinones. Moreover, singlet oxygen quantum yield of EA is superior to other kinds of photosensitizers and EA could be artificially biosynthesized at present, which make it an alternative candidate for PDT. In this review, the photophysics, photochemistry, photobiology and chemical or biological syntheses of EA photosensitizers are briefly presented. Besides, the future prospects of EA photosensitizers are also proposed.

  13. Current drug therapy and pharmaceutical challenges for Chagas disease.

    Science.gov (United States)

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection

  14. [Drug therapy in pregnancy--a practical guide].

    Science.gov (United States)

    Reister, F; Paulus, W; Kreienberg, R

    2004-03-11

    Pharmacotherapy in pregnancy is often problematic, since both the mother-to-be and her doctor are often concerned about possible risks for the unborn child. On the other hand, we now have sufficient knowledge of a whole range of medications, to enable the recommendation of safe drug treatment in almost any clinical situation. The family doctor, too, is often consulted by pregnant women requiring treatment for internistic problems. These include such pregnancy-unrelated problems as essential hypertension or bronchial asthma, as well as pregnancy-related disorders such as urinary tract infection or gastrointestinal problems.

  15. Will Drug Resistance against Dolutegravir in Initial Therapy Ever Occur?

    Directory of Open Access Journals (Sweden)

    Mark eWainberg

    2015-04-01

    Full Text Available Dolutegravir (DTG is a second-generation integrase strand transfer inhibitor (INSTI and INSTIs are the latest class of potent anti-HIV drugs. Compared to the first generation INSTIs, raltegravir (RAL and elvitegravir (EVG, DTG shows a limited cross-resistance profile. More interestingly, clinical resistance mutations to DTG in treatment-naive patents have not been observed to this date. This review summarizes recent studies on resistance mutations to DTG and on our understanding of the mechanisms of resistance to DTG as well as future directions for research.

  16. Polydioxanone-based bio-materials for tissue engineering and drug/gene delivery applications.

    Science.gov (United States)

    Goonoo, Nowsheen; Jeetah, Roubeena; Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2015-11-01

    Since the commercialization of polydioxanone (PDX) as a biodegradable monofilament suture by Ethicon in 1981, the polymer has received only limited interest until recently. The limitations of polylactide-co-glycolide (PLGA) coupled with the growing need for materials with enhanced features and the advent of new fabrication techniques such as electrospinning have revived interest for PDX in medical devices, tissue engineering and drug delivery applications. Electrospun PDX mats show comparable mechanical properties as the major structural components of native vascular extracellular matrix (ECM) i.e. collagen and elastin. In addition, PDX's unique shape memory property provides rebound and kink resistance when fabricated into vascular conduits. The synthesis of methyl dioxanone (MeDX) monomer and copolymers of dioxanone (DX) and MeDX have opened up new perspectives for poly(ester-ether)s, enabling the design of the next generation of tissue engineering scaffolds for application in regenerating such tissues as arteries, peripheral nerve and bone. Tailoring of polymer properties and their formulation as nanoparticles, nanomicelles or nanofibers have brought along important developments in the area of controlled drug or gene delivery. This paper reviews the synthesis of PDX and its copolymers and provides for the first time an exhaustive account of its applications in the (bio)medical field with focus on tissue engineering and drug/gene delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Crystal Engineering of HIV-1 Reverse Transcriptase for structure-Based Drug Design

    Energy Technology Data Exchange (ETDEWEB)

    Bauman,J.; Das, K.; Ho, W.; Baweja, M.; Himmel, D.; Clark, A.; Oren, D.; Shatkin, A.; Arnold, E.

    2008-01-01

    HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at {approx}2.5-3.0 Angstroms resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 Angstroms resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 Angstroms resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs.

  18. Effective Infusion Therapy of Drug-Induced Liver and Pancreas Injuries in Patients with Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    N.B. Gubergrits

    2013-08-01

    Full Text Available The authors examined 328 patients with pulmonary tuberculosis who had drug-induced hepatitis and drug-induced pancreatitis due to polychemotherapy. Patients had metabolic intoxication syndrome associated with increasing level of «average molecules» in the blood. Not only reliable decrease of this indicator but also its normalization was achieved under the influence of treatment with a usage of succinic acid preparation for infusion therapy.

  19. Bacterial Cellulose Membranes as a Potential Drug Delivery System for Photodynamic Therapy of Skin Cancer

    OpenAIRE

    Peres,Maristela F. S.; Nigoghossian,Karina; Primo,Fernando L.; Saska,Sybele; Capote,Ticiana S. O.; Caminaga,Raquel M. S.; Messaddeq,Younes; Ribeiro,Sidney J. L.; Tedesco,Antonio C.

    2016-01-01

    The development of drug delivery systems for photodynamic therapy (PDT) is increasingly demanded due to the hydrophobicity presented by most of photosensitizers molecules. Bacterial cellulose (BC), a highly pure cellulose produced by bacteria, possesses the essential features for applications in drug delivery systems, such as large surface area and excellent loading capacity. BC membranes prepared containing a photosensitizer, chloroaluminum phthalocyanine (ClAlPc), were tested aiming applica...

  20. Preeclampsia – will Orphan Drug Status facilitate innovative biological therapies?

    Directory of Open Access Journals (Sweden)

    Sinuhe eHahn

    2015-02-01

    Full Text Available It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia be accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture which relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in angiogenic growth factors, complement activation, reduced levels of placenta protein 13 or excessive neutrophil activation evident in preeclampsia.

  1. Preeclampsia - will orphan drug status facilitate innovative biological therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia.

  2. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy

    DEFF Research Database (Denmark)

    Denmeade, Samuel R; Mhaka, Annastasiah M; Rosen, D Marc

    2012-01-01

    Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium...

  3. Antithyroid Drug Therapy for Graves’ Disease and Implications for Recurrence

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2017-01-01

    Full Text Available Graves’ disease (GD is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD, radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors. Of these influencing factors, some are modifiable but some are nonmodifiable. The recurrence risk can be reduced by adjusting the modifiable factors as much as possible. The titration regimen for 12–18 months is the optimal strategy of ATD. Levothyroxine administration after successful ATD treatment was not recommended. The addition of immunosuppressive drugs might be helpful to decrease the recurrence rate of GD patients after ATD withdrawal, whereas further studies are needed to address the safety and efficacy. This paper reviewed the current knowledge of ATD treatment and mainly focused on influencing factors for recurrence in GD patients with ATD treatment.

  4. Association between duration of breastfeeding and drug therapy

    Directory of Open Access Journals (Sweden)

    Roberto Gomes Chaves

    2011-09-01

    Full Text Available Objective: To evaluate the existence of an association between the use of medication by nursing women and duration of breastfeeding in Itaúna, MG, Brazil. Methods: Longitudinal cohort study was carried out with 12-month follow-up, including 246 women admitted in the only Maternity Hospital of the city of Itaúna, MG, Brazil. The effect of medications on duration of breastfeeding was analyzed with the Cox regression model, with time-dependent covariables. Drugs were classified for safety during breastfeeding according to criteria established by the American Academy of Pediatrics (2001 and Hale (2004. Results: Ninety-eight percent of nursing women used medications after hospital discharge. The duration of breastfeeding was longer for mothers who did not use medications or who used drugs considering safety during lactation (P<0.05. Conclusions: Health professionals should prescribe medications with well established safety for both infants and for the lactation process, so that maternal medication is compatible with breastfeeding.

  5. Targeted drug delivery for cancer therapy: the other side of antibodies

    Science.gov (United States)

    2012-01-01

    Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients. PMID:23140144

  6. Targeted drug delivery for cancer therapy: the other side of antibodies

    Directory of Open Access Journals (Sweden)

    Firer Michael A

    2012-11-01

    Full Text Available Abstract Therapeutic monoclonal antibody (TMA based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs, particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients.

  7. Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design.

    Science.gov (United States)

    Ticehurst, Martyn David; Marziano, Ivan

    2015-06-01

    This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised. A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery. © 2015 Royal Pharmaceutical Society.

  8. Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery.

    Science.gov (United States)

    Agarwal, Pranay; Wang, Hai; Sun, Mingrui; Xu, Jiangsheng; Zhao, Shuting; Liu, Zhenguo; Gooch, Keith J; Zhao, Yi; Lu, Xiongbin; He, Xiaoming

    2017-07-25

    Development of high-fidelity three-dimensional (3D) models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumors, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis and for developing effective therapeutic strategy to fight against cancer.

  9. Manufacturing Techniques and Surface Engineering of Polymer Based Nanoparticles for Targeted Drug Delivery to Cancer

    Directory of Open Access Journals (Sweden)

    Yichao Wang

    2016-02-01

    Full Text Available The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide (PLGA and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA and European Medicine Agency (EMA, making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined.

  10. Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

    Science.gov (United States)

    Villa, Jordan C; Gianakos, Arianna; Lane, Joseph M

    2016-02-01

    Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer-review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options.

  11. Accelerating the semisynthesis of alkaloid-based drugs through metabolic engineering.

    Science.gov (United States)

    Ehrenworth, Amy M; Peralta-Yahya, Pamela

    2017-02-15

    Alkaloid-derived pharmaceuticals are commonly semisynthesized from plant-extracted starting materials, which often limits their availability and final price. Recent advances in synthetic biology have enabled the introduction of complete plant pathways into microbes for the production of plant alkaloids. Microbial production of modified alkaloids has the potential to accelerate the semisynthesis of alkaloid-derived drugs by providing advanced intermediates that are structurally closer to the final pharmaceuticals and could be used as advanced intermediates for the synthesis of novel drugs. Here, we analyze the scientific and engineering challenges that must be overcome to generate microbes to produce modified plant alkaloids that can provide more suitable intermediates to US Food and Drug Administration-approved pharmaceuticals. We highlight modified alkaloids that currently could be produced by leveraging existing alkaloid microbial platforms with minor variations to accelerate the semisynthesis of seven pharmaceuticals on the market.

  12. Bioproduction of Antibody-Drug Conjugate Payload Precursors by Engineered Cell Factories.

    Science.gov (United States)

    Wang, Jie; Xiao, Han; Qian, Zhi-Gang; Zhong, Jian-Jiang

    2017-05-01

    Antibody-drug conjugates (ADCs), which combine the exquisite specificity of antibodies with the cell-killing ability of cytotoxic drug payloads, have emerged as an attractive means for treating cancers. All (pre)clinical ADCs employ biosynthesized cytotoxins as their ADC payload precursors (APPs). The cost-effective bioproduction of APPs is receiving great interest from both academia and industry. Given the lack of systematic overviews of the topic, we provide the current status of APPs and focus on their state-of-the-art bioproduction strategies, illustrated with typical examples and critical analyses. Challenges in further enhancing the bioproduction efficiency of APPs and other cytotoxins are also discussed. This research has implications for bioprocess and metabolic engineering, systems and synthetic biology, and biopharmaceutical drug discovery, development, and industrialization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Indefinite antithyroid drug therapy in toxic Graves′ disease: What are the cons

    Directory of Open Access Journals (Sweden)

    Rajesh Rajput

    2013-01-01

    Full Text Available Existing treatment modalities for Graves′ disease includes antithyroid drugs (ATDs, radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves′ disease after discussing this with the patient.

  14. Complementary and alternative drug therapy versus science-oriented medicine

    Science.gov (United States)

    Anlauf, Manfred; Hein, Lutz; Hense, Hans-Werner; Köbberling, Johannes; Lasek, Rainer; Leidl, Reiner; Schöne-Seifert, Bettina

    2015-01-01

    This opinion deals critically with the so-called complementary and alternative medical (CAM) therapy on the basis of current data. From the authors’ perspective, CAM prescriptions and most notably the extensive current endeavours to the “integration” of CAM into conventional patient care is problematic in several respects. Thus, several CAM measures are used, although no specific effects of medicines can be proved in clinical studies. It is extensively explained that the methods used in this regard are those of evidence-based medicine, which is one of the indispensable pillars of science-oriented medicine. This standard of proof of efficacy is fundamentally independent of the requirement of being able to explain efficacy of a therapy in a manner compatible with the insights of the natural sciences, which is also essential for medical progress. Numerous CAM treatments can however never conceivably satisfy this requirement; rather they are justified with pre-scientific or unscientific paradigms. The high attractiveness of CAM measures evidenced in patients and many doctors is based on a combination of positive expectations and experiences, among other things, which are at times unjustified, at times thoroughly justified, from a science-oriented view, but which are non-specific (context effects). With a view to the latter phenomenon, the authors consider the conscious use of CAM as unrevealed therapeutic placebos to be problematic. In addition, they advocate that academic medicine should again systematically endeavour to pay more attention to medical empathy and use context effects in the service of patients to the utmost. The subsequent opinion discusses the following after an introduction to medical history: the definition of CAM; the efficacy of most common CAM procedures; CAM utilisation and costs in Germany; characteristics of science-oriented medicine; awareness of placebo research; pro and contra arguments about the use of CAM, not least of all in terms

  15. Complementary and alternative drug therapy versus science-oriented medicine

    Directory of Open Access Journals (Sweden)

    Anlauf, Manfred

    2015-06-01

    Full Text Available This opinion deals critically with the so-called complementary and alternative medical (CAM therapy on the basis of current data. From the authors’ perspective, CAM prescriptions and most notably the extensive current endeavours to the “integration” of CAM into conventional patient care is problematic in several respects.Thus, several CAM measures are used, although no specific effects of medicines can be proved in clinical studies. It is extensively explained that the methods used in this regard are those of evidence-based medicine, which is one of the indispensable pillars of science-oriented medicine. This standard of proof of efficacy is fundamentally independent of the requirement of being able to explain efficacy of a therapy in a manner compatible with the insights of the natural sciences, which is also essential for medical progress. Numerous CAM treatments can however never conceivably satisfy this requirement; rather they are justified with pre-scientific or unscientific paradigms. The high attractiveness of CAM measures evidenced in patients and many doctors is based on a combination of positive expectations and experiences, among other things, which are at times unjustified, at times thoroughly justified, from a science-oriented view, but which are non-specific (context effects. With a view to the latter phenomenon, the authors consider the conscious use of CAM as unrevealed therapeutic placebos to be problematic. In addition, they advocate that academic medicine should again systematically endeavour to pay more attention to medical empathy and use context effects in the service of patients to the utmost.The subsequent opinion discusses the following after an introduction to medical history: the definition of CAM; the efficacy of most common CAM procedures; CAM utilisation and costs in Germany; characteristics of science-oriented medicine; awareness of placebo research; pro and contra arguments about the use of CAM, not least

  16. Parallel demand-withdraw processes in family therapy for adolescent drug abuse.

    Science.gov (United States)

    Rynes, Kristina N; Rohrbaugh, Michael J; Lebensohn-Chialvo, Florencia; Shoham, Varda

    2014-06-01

    Isomorphism, or parallel process, occurs in family therapy when patterns of therapist-client interaction replicate problematic interaction patterns within the family. This study investigated parallel demand-withdraw processes in brief strategic family therapy (BSFT) for adolescent drug abuse, hypothesizing that therapist-demand/adolescent-withdraw interaction (TD/AW) cycles observed early in treatment would predict poor adolescent outcomes at follow-up for families who exhibited entrenched parent-demand/adolescent-withdraw interaction (PD/AW) before treatment began. Participants were 91 families who received at least four sessions of BSFT in a multisite clinical trial on adolescent drug abuse (Robbins et al., 2011). Prior to receiving therapy, families completed videotaped family interaction tasks from which trained observers coded PD/AW. Another team of raters coded TD/AW during two early BSFT sessions. The main dependent variable was the number of drug-use days that adolescents reported in timeline follow-back interviews 7 to 12 months after family therapy began. Zero-inflated Poisson regression analyses supported the main hypothesis, showing that PD/AW and TD/AW interacted to predict adolescent drug use at follow-up. For adolescents in high PD/AW families, higher levels of TD/AW predicted significant increases in drug use at follow-up, whereas for low PD/AW families, TD/AW and follow-up drug use were unrelated. Results suggest that attending to parallel demand-withdraw processes in parent-adolescent and therapist-adolescent dyads may be useful in family therapy for substance-using adolescents.

  17. Consideration of Drug Therapy in Benign Prostatic Hypertrophy

    Directory of Open Access Journals (Sweden)

    G. Diamantis

    2015-01-01

    Full Text Available Benign prostatic hypertrophy (BPH has become a major global health problem both in its frequency by which it determines the complications and the problems of diagnosis and treatment it requires. BPH is a heterogeneous disease. The symptoms attributed to BPH may have other coexisting causes and growth factors both androgen-dependent and independent, which promotes prostate enlargement. It is well known that prostate size correlates poorly with the symptoms so that reducing prostate using 5-alphareductase or alphablocants inhibitors may not always be sufficient. A better understanding of the pathophysiology of BPH and its interactions with other drugs will help the development of new substances with a better efficiency. This present work aims to be a modest contribution related to medical treatment in benign prostatic hyperplasia and the role that the generalist practitioner should play in managing of this urinary disease quite common in elderly men.

  18. Antiparasitic peptides from arthropods and their application in drug therapy

    Directory of Open Access Journals (Sweden)

    Ariane Ferreira Lacerda

    2016-02-01

    Full Text Available Africa, Asia and Latin America are regions highly affected by endemic diseases, such as Leishmaniasis, Malaria and Chagas’ disease. They are responsible for the death of thousands of patients every year, as there is not yet a cure for them and the drugs used are inefficient against the pathogenic parasites. During the life cycle of some parasitic protozoa, insects become the most important host and disseminator of the diseases triggered by these microorganisms. As infected insects do not develop nocive symptoms, they can carry the parasites for long time inside their body, enabling their multiplication and life cycle completion. Eventually, parasites infect human beings after insects transmission through their saliva and/or feces. Hence, host insects and general arthropods, which developed a way to coexist with such parasites, are a promising source for the prospection of antiparasitic compounds, as alternative methods for the treatment of protozoa-related diseases. Among the molecules already isolated and investigated, there are proteins and peptides with high activity against parasites, able to inhibit parasite activity in different stages of development. Although studies are still taking their first steps, initial results show new perspectives on the treatment of parasitic diseases. Therefore, in this report, we describe about peptides from host insect sources with activity against the three most endemic parasites: Leishmania sp, Plasmodium sp. and Trypanosomes. Moreover, we discuss the future application insect peptides as anti-parasitic drugs and the use of non-hosts insect transcriptomes on the prospection of novel molecules for the treatment of parasitic neglected diseases.

  19. Progress in antihypertensive therapy with a multiple-action drug.

    Science.gov (United States)

    Prichard, B N; Tomlinson, B

    1988-01-01

    The beta-blockers in clinical use have been classified into 2 major divisions, nonselective or selective agents, and those with or without intrinsic sympathomimetic activity (ISA). These properties confer differing pharmacological properties with some relevance to the treatment of hypertension. A beta-blocker with significant beta 2-ISA can be regarded as a multiple-action drug. A third division of beta-blockers is a newer development; these agents, besides blocking the beta-receptor, possess important peripheral vasodilator activity. Labetalol was the first drug of this group and prizidolol followed, but has been withdrawn because of toxicity. Several other agents now under evaluation include bucindolol and medroxolol, and carvedilol and dilevalol (1 of the isomers of labetalol), which have been the most widely studied in hypertension. Combined action results in important haemodynamic differences compared with pure beta-blockade. Notably, peripheral resistance is reduced, and there is less reduction in, or no effect on, cardiac output. The 3 following mechanisms have been described as responsible for peripheral vasodilatation: alpha-receptor blockade, beta 2-agonism, and a dilator action independent of either the alpha- or beta-receptors. Evidence for these various mechanisms is more readily obtainable from animal experiments, but some confirmatory evidence has been obtained in man. Inhibition of alpha-stimulation has been found with labetalol and to a small degree with medroxalol and carvedilol. beta 2-Mediated vasodilatation has been shown by dilevalol and medroxolol, and evidence of vasodilatation independent of alpha- or beta-receptors has been obtained with carvedilol. More evidence is required to confirm the exact contribution of each of these mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. DRUG THERAPY IN ASTHMATIC CHILDREN: SURVEY IN MASHHAD

    Directory of Open Access Journals (Sweden)

    M.H Karimi

    2000-03-01

    Full Text Available Introduction. For future health planning of our country, the type and amount of drugs used for treatment of chronic diseases should be known. Therefore, in the present study the treatment regimen of asthmatic children in the city of Mashhad was studied. Methods. To study the different types of drugs in the treatment regimen of asthmatic children in the city of Mashhad, we evaluated the treatment regimen of 366 primary school children with asthma disease. Starting, maximum and duration of action of three different bronchodilators (salbutamol inhaler, salbutamol syrup, and theophylline syrup were compared. Findings. The results of the first part of this study showed that only 31.6 percent of asthmatic children had history of treatment and only 10.6 percent had current medication. In addition, most of the treated children (38.8 percent had only bronchodilator (salbutamol syrup in their treatment regimen. The effect of salbutamol inhaler on lung function tests starts in 5 min, salbutamol syrup in 15 min and theophylline syrup at 30 min after administration. The maximum response to salbutamol inhaler, salbutamol syrup, and theophylline syrup occurred 15 min, 4 hr and 3 hr after administration, respectively. The reduction of response to salbutamol inhaler occurs after 3 hr, but there was no any reduction in response to salbutamol and theophylline syrup during study period. Conclusion. The prevalence of asthma among children in the city of Mashhad is relatively high, but most of asthmatic children are not treated. Although the oral bronchodilator in mild asthma is effective, salbutamol inhaler is needed for emergency use.

  1. Important Drug-Drug Interactions in HIV-Infected Persons on Antiretroviral Therapy: An Update on New Interactions Between HIV and Non-HIV Drugs.

    Science.gov (United States)

    Tseng, Alice; Foisy, Michelle

    2012-02-01

    Advances in antiretroviral therapy have turned HIV into a chronic, manageable disease. Patients often require treatment for co-morbid conditions as well as HIV, and consequently, pharmacokinetic interactions between antiretrovirals (ARVs) and other drug classes are an increasing concern. Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are involved in the CYP450 or other transporter systems, and may be associated with higher risk of clinically significant drug interactions. One reverse transcriptase inhibitor, abacavir, has demonstrated weak inhibition of CYP3A4, 2D6 and 2C9 in vitro, but is not associated with any clinically significant interactions involving the CYP450 system. The integrase inhibitor raltegravir is not involved in the CYP450 system, and may be a suitable option to use when trying to minimize interactions with other drug classes. This review summarizes recently published data on clinically significant drug interactions between ARVs and other drug classes including antineoplastics, immunosuppressant transplant drugs, directly acting antivirals for hepatitis C, antifungals, antimalarials, corticosteroids, psychotropics, hormonal contraceptives, anticoagulants, drugs for pulmonary hypertension, and herbal products. In situations of suspected or potential interactions, close monitoring is warranted, and dose adjustments or substitutions may be required.

  2. Episcleritis Related to Drug-Induced Lupus Erythematosus following Infliximab Therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Irini P. Chatziralli

    2011-01-01

    Full Text Available Drug-induced lupus erythematosus is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. Herein, we describe a patient with distinct clinical manifestations of anti-TNF-associated DILE related to infliximab therapy. The patient exhibited clinical and laboratory findings of lupus-like illnesses as well as ocular disorders, such as episcleritis. The main message is that the symptoms of DILE should not be overlooked, although sometimes other systematic conditions may underlie them. As a result, it is very important for the clinicians to evaluate the symptoms of DILE and manage appropriately these cases.

  3. Brief strategic family therapy for young people in treatment for drug use

    DEFF Research Database (Denmark)

    Lindstrøm, Maia; Filges, Trine; Jørgensen, Anne-Marie Klint

    2015-01-01

    This review evaluates the evidence on the effects of brief strategic family therapy (BSFT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to prepare this review and ultimately located three studies for final analysis...... and interpretation. Results: The results are mixed: BSFT does not seem to have better or worse effects on drug use frequency and family functioning than other treatments but has positive effects on treatment retention compared to control conditions. Longer retention in treatment has been identified as a consistent...

  4. Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

    Science.gov (United States)

    2012-01-01

    Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009) from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%), followed by valproic acid (23%), mirtazapine and venlafaxine (16% each), quetiapine (15%), lamotrigine (14%) and olanzapine (13%). Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI), but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined) was the most frequently prescribed drug (39%); aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine) with mood stabilizers (lithium, valproic acid, lamotrigine) and / or atypical antipsychotics (quetiapine, olanzapine) are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines. PMID:22998655

  5. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

    Science.gov (United States)

    Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.

    2012-01-01

    Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

  6. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

    Directory of Open Access Journals (Sweden)

    Tinashe Mudzviti

    2012-01-01

    Full Text Available Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART. Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2% of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%, Bidens pilosa (66.0%, Eucalyptus globulus (52.3%, Moringa oleifera (44.1%, Lippia javanica (36.3%, and Peltoforum africanum (34.3%. Two indigenous herbs, Musakavakadzi (OR=0.25; 95% CI 0.076–0.828 and Peltoforum africanum (OR=0.495; 95% CI 0.292–0.839 reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

  7. Non-Drug Therapy and Prevention of Diabetes Mellitus by Dalk (Massage).

    Science.gov (United States)

    Bayat, Davood; Vakilinia, Seyed Reza; Asghari, Majid

    2016-05-01

    According to WHO estimation, the number of diabetic patients would reach about 591.9 million people in 2035. The tendency towards other kinds of treatment is increasing because of the high therapeutic expenditures and current medical complications. Positive results of massage in recent articles and the prominent role of dalk in Iranian traditional medicine led us to the present study review. Studying Iranian traditional medicine textbooks, such as Canon of Ibn Sina, Kholasat Al Hekma of Aghili, Zakhireh-ye Khwarazm shahi of Jorjani, Alhavi of Razes and Kamel-al-sanaat of Ibn Abas were done on the topic of dalk discussion. Additionally, a search on "massage and diabetes mellitus" articles was done in motor search engines of PubMed, Google Scholars and the site of "Farhangestane Oloume Pezeshki". The data were eventually compared and evaluated. In Iranian traditional medicine, dalk means kneading or massage of the body. Depending on the quality and quantity of the performance, it was divided into different kinds. The mechanism of dalk is to increase the blood supply in organs and subsequently increasing organ's warmness and metabolism that lead to increased residues expulsion. Therefore, it could be advised to healthcare system as a means of treatment. On the other hand, for different diseases such as asthma, arthritis, insomnia, paralysis, DM, and constipation the effect of massage was evaluated and its positive results were confirmed. For example, in DM, its effects in decreasing FBS and HBA1C are shown. According to Iranian traditional medicine and latest articles, dalk as a non-drug therapy and prevention manner is recommended.

  8. [Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)].

    Science.gov (United States)

    Morabito, S; Guzzo, I; Vitaliano, E; Muzi, L; Solazzo, A; Pistolesi, V; Pierucci, A

    2006-01-01

    In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

  9. [Difficulties in the transfer of drug therapy from inpatient to ambulatory treatment].

    Science.gov (United States)

    Adl, S; Weltermann, B M; Küching, A; Martin, C; Korbonits, G; Höpp, H W

    2001-10-01

    The prospective study compares prescribed drugs of 192 primarily cardiological patients at discharge and 7 weeks later in ambulatory care. The data were determined by discharge summaries and by standardized patient-questionnaires. The drug division was made with the ATC-classification according to the recommendations of the World Health Organisation for Drug Utilisation Studies. The intraindividual cost comparison was calculated by current pharmacy sale prices. The findings were changes in hospital discharge medications in ambulatory care in over 2/3 of the cases. The most frequent change was the additional prescribing of drug groups. The average daily tablet number increased in patients with the same or worsened subjective feeling after discharge. Additionally we found in a number of patients a change of drug therapy within the ATC-groups, or in fact, withdrawal of drug therapy all together. The frequency of changes increased with the number of patient/doctor contacts. The observation that the average daily therapeutical cost decreased just slightly could give an indication that cost saving was a minor part of the doctors decision for drug changing. However, the frequency of changes has shown to be dependent upon the specialities of the physician or pharmaceutical group.

  10. Evaluation of short course drug therapy for tuberculosis in pediatric ward of Imam Khomeini Hospital

    Directory of Open Access Journals (Sweden)

    Daneshjoo Kh

    1999-07-01

    Full Text Available Tuberculosis appears to be a disease as old as human history. Tuberculosis is of great public health importance in the developing countries. Its clinical profile is different in developing countries in comparison to countries of Europe and North America. The recent epidemic of HIV has slowed down the declining trend in the incidence of tuberculosis. Bacilli are transmitted from one infected person to the others as an aerosol. In some cases contaminated milk may also be responsible. However despite effective regimens and addition of new drugs and improved pharmacokinetic knowledge the chemotherapy of tuberculosis still remains a challenge. Poor drug-compliance by patients being one of the foremost reason for frequent relapses and bacterial resistance. Some important and concrete steps to meet these challenges have been judicious use of two or more bactericidal drugs and introduction of short courses regiment. Multiple drugs therapy may shorten the duration of treatment and prevent emergence of drug resistance.

  11. Functional Family Therapy for Young People in Treatment for Nonopioid Drug Use

    DEFF Research Database (Denmark)

    Filges, Trine; Andersen, Ditte

    2016-01-01

    Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized...... and nonrandomized trials. Results: The search yielded two studies that met inclusion criteria. Only one study provided numerical results on the effect of FFT on drug use reduction. Conclusions: There is insufficient evidence to allow any conclusion to be drawn on the effect of FFT for young people in treatment...... for nonopioid drug use. There is a need for more research and particularly for more methodologically rigorous studies in the field of treatment for young drug users....

  12. An overview of anti-allergic drug therapy and the histamine-1 ...

    African Journals Online (AJOL)

    and corticosteroid medication (when indicated, and in most instances, used locally). The article provides an overview of the nature and the management of allergic disease and the histamine 1 antihistamines. Keywords: anti-allergic drug therapy, H1 antihistamines, histamine receptors, allergic rhinoconjunctivitis, allergy ...

  13. Lessons Learned from Gemcitabine: Impact of Therapeutic Carrier Systems and Gemcitabine's Drug Conjugates on Cancer Therapy.

    Science.gov (United States)

    Dyawanapelly, Sathish; Kumar, Animesh; Chourasia, Manish K

    2017-01-01

    Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored. This review outlines the recent work directed toward gemcitabine delivery systems for cancer therapy, including aerosols, polymeric nanoparticles, liposomes, microparticles, carbon nanotubes, and multifunctional theranostic nanomedicines. It also provides insight into the design and development of gemcitabine conjugation for safe and effective cancer therapy. Despite the clinical promises of gemcitabine, many therapeutic challenges remain. Specifically, its therapeutic use in cancer chemotherapy is impeded by a short biological half-life, caused by its rapid metabolism, and resistance due to increased expression of ribonucleotide reductase. In our opinion, many research investigations have contributed to improve the selectivity and efficacy of gemcitabine. This combined approach of drug delivery systems and gemcitabine conjugates has shown promising efficacy in preclinical models and significant potential for future clinical cancer-therapeutic applications. Also, these strategies overcome most of the aforementioned limits of gemcitabine.

  14. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

  15. Liposomes as a drug delivery system in photodynamic therapy for colon cancer treatment

    CSIR Research Space (South Africa)

    Maduray, K

    2010-01-01

    Full Text Available Photodynamic therapy (PDT) uses a drug termed a photosensitizer (PS), light (laser) of an appropriate wavelength and molecular oxygen (tissue) to elicit cell death of cancer cells. The objective of this study was to evaluate the enhancement of PDT...

  16. Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper

    2011-01-01

    Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients...

  17. Pharmacy Characteristics Associated with the Provision of Drug Therapy Services in Nonmetropolitan Community Pharmacies

    Science.gov (United States)

    Gadkari, Abhijit S.; Mott, David A.; Kreling, David H.; Bonnarens, Joseph K.

    2009-01-01

    Context: Higher prevalence of chronic diseases and reduced access to other health professionals in rural areas suggest that rural Medicare enrollees will benefit from pharmacist-provided drug therapy services (DTS). Purpose: The purpose of this study was to describe non-metropolitan community pharmacy sites in Wisconsin, the provision of DTS at…

  18. Biologically Inspired Polydopamine Capped Gold Nanorods for Drug Delivery and Light-Mediated Cancer Therapy.

    Science.gov (United States)

    Wang, Shaowei; Zhao, Xinyuan; Wang, Shaochuan; Qian, Jun; He, Sailing

    2016-09-21

    Multifunctional drug delivery and combined multimodal therapy strategies are very promising in tumor theranostic applications. In this work, a simple and versatile nanoplatform based on biologically inspired polydopamine capped gold nanorods (GNR-PDA) is developed. Dopamine, a well-known neurotransmitter associated with many neuronal disorders, can undergo self-polymerization on the surface of GNRs to form a stable PDA shell. Its unique molecular adsorption property, as well as its high chemical stability and biocompatibility, facilitate GNR-PDA as an ideal candidate for drug delivery. Methylene blue (MB) and doxorubicin (DOX) are directly adsorbed on GNR-PDA via electrostatic and/or π-π stacking interactions, forming GNR-PDA-MB and GNR-PDA-DOX nanocomposites, respectively. The GNR-PDA-MB can generate reactive oxygen species (ROS, from MB) or hyperthermia (from GNR-PDA) with high efficiency under deep-red/NIR laser irradiation, while the GNR-PDA-DOX exhibits light-enhanced drug release under NIR laser irradiation. The combined dual-modal light-mediated therapy, by using GNR-PDA-MB [photodynamic/photothermal therapy (PDT/PTT)] and GNR-PDA-DOX (Chemo/PTT), is carried out and shows remarkable cancer cell killing efficiency in vitro and significant suppression of tumor growth in vivo, which are much more distinct than any single-modal therapy strategy. Our work illustrates that GNR-PDA could be a promising nanoplatform for multifunctional drug delivery and multimodal tumor theranostics in the future.

  19. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Science.gov (United States)

    2010-10-01

    ... and systems to reduce medication errors and adverse drug interactions and improve medication use that... medication error identification and reduction systems. (5) Provision of information to CMS regarding its... medication therapy management programs (MTMPs). 423.153 Section 423.153 Public Health CENTERS FOR MEDICARE...

  20. Effects of aerobic exercise and drug therapy on blood pressure and ...

    African Journals Online (AJOL)

    EB

    Abstract. Background: Although aerobic exercise has been shown to lower blood pressure (BP) in human beings, its additive BP- reducing effect on antihypertensive drug therapy seems to have been investigated in only laboratory animals. Objectives: This study investigated the effects of aerobic dance combined with ...

  1. Effects of aerobic exercise and drug therapy on blood pressure and ...

    African Journals Online (AJOL)

    EB

    reducing effect on antihypertensive drug therapy seems to have been investigated in only laboratory animals. Objectives: This study investigated the effects of .... pregnant or diabetic or had a history of coronary or valvular heart, renal, cerebral vascular, ... Participants with recent history of smoking and alcohol abuse (<6 ...

  2. Application of the Pareto principle to identify and address drug-therapy safety issues.

    Science.gov (United States)

    Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

    2014-06-01

    Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

  3. Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

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    Juan D Unciti-Broceta

    2015-06-01

    Full Text Available African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

  4. ANTIHYPERTENSIVE DRUG THERAPY FOR HYPERTENSIVE DISORDERS IN PREGNANCY

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    Slobodan Jankovic

    2008-10-01

    Full Text Available Hypertension in pregnancy is associated with increased maternal and fetal mortality and morbidity. About 8 % of all pregnancies are complicated with hypertensive disorders. There is concordance that severe hypertension should be treated without delay to reduce maternal risks of acute cerebrovascular complications. Intravenous labetalol and oral nifedipine are as effective as intravenous hydralazine in control of severe hypertension, with less adverse effects. Still, there is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated, considering that there are no definitive conclusions which can be made about the relative maternal or perinatal benefits/risks of antihypertensive treatment. Considering their safe usage during pregnancy, methyldopa, labetalol and nifedipine are commonly used blood-pressure lowering drugs for pregnant women with hypertension. The cardio-selective β- blocker atenolol should be avoided in pregnancy, because it has been associated with lower birth weights and fetal growth impairment. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy.

  5. Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma.

    Science.gov (United States)

    Kalimuthu, Senthilkumar; Jeong, Ju Hye; Oh, Ji Min; Ahn, Byeong-Cheol

    2017-07-27

    Molecular imaging allows a noninvasive assessment of biochemical and biological processes in living subjects. Treatment strategies for malignant lymphoma depend on histology and tumor stage. For the last two decades, molecular imaging has been the mainstay diagnostic test for the staging of malignant lymphoma and the assessment of response to treatment. This technology enhances our understanding of disease and drug activity during preclinical and clinical drug development. Here, we review molecular imaging applications in drug development, with an emphasis on oncology. Monitoring and assessing the efficacy of anti-cancer therapies in preclinical or clinical models are essential and the multimodal molecular imaging approach may represent a new stage for pharmacologic development in cancer. Monitoring the progress of lymphoma therapy with imaging modalities will help patients. Identifying and addressing key challenges is essential for successful integration of molecular imaging into the drug development process. In this review, we highlight the general usefulness of molecular imaging in drug development and radionuclide-based reporter genes. Further, we discuss the different molecular imaging modalities for lymphoma therapy and their preclinical and clinical applications.

  6. Drug Therapy in Atrial Fibrillation Management: Where Do We Stand in 2010?

    Directory of Open Access Journals (Sweden)

    Mehdi Montazeri

    2010-11-01

    Full Text Available Atrial fibrillation (AF is a commonly encountered arrhythmia in our daily practice. Every year a huge bulk of data is published about different management strategies, new antiarrhythmic drugs, anticoagulation protocols and ablation procedures in these patients. In this review article, we discuss different management strategies and new antiarrhythmic drugs as well as those commonly used. We will also have a brief look at anticoagulation in AF.We try to introduce the most recent publications in this field and we think that this review article may not only give information about the current state of antiarrhythmic therapy of AF, it may also show some progresses that we may anticipate in the near future. New drugs are promising in the management of AF because of better safety profile and also acceptable efficacy. A comparison between the catheter ablation procedure and antiarrhythmic therapy is beyond the scope of this article.

  7. Current therapies and future possibilities for drug development against liver-stage malaria.

    Science.gov (United States)

    Raphemot, Rene; Posfai, Dora; Derbyshire, Emily R

    2016-06-01

    Malaria remains a global public health threat, with half of the world's population at risk. Despite numerous efforts in the past decade to develop new antimalarial drugs to surmount increasing resistance to common therapies, challenges remain in the expansion of the current antimalarial arsenal for the elimination of this disease. The requirement of prophylactic and radical cure activities for the next generation of antimalarial drugs demands that new research models be developed to support the investigation of the elusive liver stage of the malaria parasite. In this Review, we revisit current antimalarial therapies and discuss recent advances for in vitro and in vivo malaria research models of the liver stage and their importance in probing parasite biology and the discovery of novel drug candidates.

  8. Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery.

    Science.gov (United States)

    Murata, Mitsushige; Tohyama, Shugo; Fukuda, Keiichi

    2010-05-01

    Although stem-cell technology holds great promise for the treatment of degenerative diseases and the development of new drugs, progress has been hindered by immune and ethical problems in association with the use of embryonic stem cells (ESCs). The recent development of reprogramming of differentiated human somatic cells to pluripotent stem cells (iPSCs) should overcome these obstacles and facilitate clinical applications of stem cells. One of the advantages of reprogramming is that it allows the establishment of patient- and disease-specific in vitro models of human hereditary diseases for pathophysiologic and developmental studies. These in vitro models can be used for drug development and testing, moving us a step closer to personalized therapies. This review outlines the current status of pluripotent stem cells and focuses on the potential applications of stem cell-derived cardiomyocytes for clinical therapies, as well as for drug development and testing. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Tumor-Targeting Therapy Using Gene-Engineered Anaerobic-Nonpathogenic Bifidobacterium longum.

    Science.gov (United States)

    Taniguchi, Shun'ichiro; Shimatani, Yuko; Fujimori, Minoru

    2016-01-01

    Despite great progress in molecular-targeting drugs for cancer treatment, there are problems of disease recurrence due to cancer-cell resistance to those drugs, derived from the heterogeneity of tumors. On one hand, the low-oxygen microenvironment present in malignant tumor tissues has been regarded as a source of resistance of cancer cells against conventional therapie, such as radiation and chemotherapy. To overcome these problems, we have been developing a system to selectively deliver a large amount of anticancer drugs to malignant tumors by making use of the limiting factor, hypoxia, in tumors. Our strategy is to use hypoxia as a selective target. Here, we show methods and protocols using the nonpathogenic obligate anaerobic Bifidobacterium longum as a drug-delivery system (DDS) to target anaerobic tumor tissue.

  10. Impact of a transition to more restrictive drug formulary on therapy discontinuation and medication adherence.

    Science.gov (United States)

    Shirneshan, E; Kyrychenko, P; Matlin, O S; Avila, J P; Brennan, T A; Shrank, W H

    2016-02-01

    There is conclusive evidence demonstrating that formulary restrictions are associated with reduced utilization and pharmacy spending of the restricted drugs. However, prior efforts to implement restrictive formularies have been associated with inconsistent rates of therapy discontinuation and mixed impacts on adherence to therapy. Also, the impact of transferring patients from an already restrictive formulary to a more aggressive model has not been previously examined. This study evaluated the impact of implementation of a more restrictive formulary on therapy disruption, adherence rates, pharmacy costs and generic utilization among patients with common chronic conditions. In 2014, CVS Health implemented Value Formulary (VF), a restrictive benefit design with the aim of reducing spending while preserving access to and adherence to essential therapy, was used. A retrospective cohort study was conducted to assess changes in therapy disruption rates, pharmacy costs and generic dispensing rate (GDR) (for continuers) and medication adherence (for initiators) following the implementation of VF. The study group was selected from members of three existing employer clients transitioned from standard formulary (SF) to VF on January 2014. The control population was a matched group of six employers with the same preperiod formulary structure, business unit, adherence programmes and patient out-of-pocket cost as the study group. The control group retained SF in 2014. To assess therapy disruption after VF implementation, we categorized patients by their subsequent medication use into three groups: (i) therapy stopped, (ii) therapy continued and (iii) therapy switched. Medication adherence was measured as monthly proportion of days covered (PDC). Pharmacy cost and GDR were measured per utilizer per month (PUPM). Rates of therapy disruption in study and control groups were compared using the chi-square test. Differences in monthly PDC between matched groups were evaluated using

  11. Effects of hospital generic drug substitution on diabetes therapy

    Directory of Open Access Journals (Sweden)

    Chen HY

    2014-01-01

    Full Text Available Hui-Yin Chen,1 Hui-Ru Chang,2 Hui-Chu Lang3 1Department of Auditing, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Social Insurance, Ministry of Health and Welfare, Taipei, Taiwan; 3Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan Objectives: To evaluate the effects on physicians’ prescribing behavior and on the therapeutic outcome of non-insulin-dependent diabetes patients of substituting different generic brands of metformin. Methods: We adopt a retrospective cohort study involving 280 type-2 diabetes patients who regularly used the outpatient services of one medical center and who had changed metformin brands five times between 2003 and 2008. The aim was to examine the effects of switching brands. The generalized estimating equation was used to determine whether drug brand switching affected patient glycated hemoglobin A1c (HbA1c levels, their prescribed daily dose, or their adherence to medication with metformin. Results: HbA1c levels increased from 7.91 to 8.34 throughout the study period, although it was found that brand switching did not adversely affect HbA1c levels after controlling for patient characteristics and the time course of the study. Furthermore, the prescribed daily dose of metformin was stable throughout the study period, and was approximately 0.8 of the defined daily dose. Finally, although adherence was significantly higher with the original metformin than with the four generic brands, patients still maintained high levels of adherence of >0.8. Conclusion: Although switching between different brands of metformin slightly affected the prescribing behavior of the physicians, there was no unfavorable effect on patient HbA1c levels. Thus, the policy of substituting between different generic brands of metformin is a good cost-effective approach that does not adversely affect the quality of diabetes patient care. Keywords: metformin, generic substitution, glycemic

  12. Nano and microparticle engineering of water insoluble drugs using a novel spray-drying process.

    Science.gov (United States)

    Schafroth, Nina; Arpagaus, Cordin; Jadhav, Umesh Y; Makne, Sushil; Douroumis, Dennis

    2012-02-01

    In the current study nano and microparticle engineering of water insoluble drugs was conducted using a novel piezoelectric spray-drying approach. Cyclosporin A (CyA) and dexamethasone (DEX) were encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) grades of different molecular weights. Spray-drying studies carried out with the Nano Spray Dryer B-90 employed with piezoelectric driven actuator. The processing parameters including inlet temperature, spray mesh diameter, sample flow rate, spray rate, applied pressure and sample concentration were examined in order to optimize the particle size and the obtained yield. The process parameters and the solute concentration showed a profound effect on the particle engineering and the obtained product yield. The produced powder presented consistent and reproducible spherical particles with narrow particle size distribution. Cyclosporin was found to be molecularly dispersed while dexamethasone was in crystalline state within the PLGA nanoparticles. Further evaluation revealed excellent drug loading, encapsulation efficiency and production yield. In vitro studies demonstrated sustained release patterns for the active substances. This novel spray-drying process proved to be efficient for nano and microparticle engineering of water insoluble active substances. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Genetic engineering of bio-nanoparticles for drug delivery: a review.

    Science.gov (United States)

    Nishimura, Yuya; Ishii, Jun; Ogino, Chiaki; Kondo, Akihiko

    2014-09-01

    Techniques using nanotechnology in the detection and treatment of cancers have made great progress in multidisciplinary fields. The advances in drug delivery systems (DDSs) have been supported mainly by the development of varied nanoparticles (NPs). Although the NPs based on organic and inorganic materials are integral parts in DDSs, bio-nanoparticles containing biopolymer and virus-like particles (VLPs) are attractive biomaterials for DDSs because of their unique features originating in bio-based materials, such as biocompatibility, biodegradability and low immunogenicity. It is notable that these NPs additionally have a great advantage to enable the easy and flexible alteration of their features by genetic engineering approaches. Controlling the sequence and oligomeric process of polypeptide genes permits a variety of choices in type or size of biopolymeric NPs (e.g., elastin-like polypeptide NPs). In contrast, the functional genes are often inserted into the coding sequences for self-assembled proteins to give the VLPs (e.g., hemagglutinating virus of Japan, adeno-associated virus, human immunodeficiency virus-1, simian virus 40 and hepatitis B virus) additional functions. Thus, genetic engineering readily allow alterations of the properties of NPs (e.g., particle shape, size and stability) and grant of new abilities (e.g., cell-specificity and drug loading and release). In this review, we introduce recent advances in bio-nanoparticles from the standpoint of engineering.

  14. Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

    Science.gov (United States)

    Hodgkinson, Conrad P.; Gomez, José A.; Mirotsou, Maria

    2010-01-01

    Abstract The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed. PMID:20825283

  15. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

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    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  16. Public versus Private Drug Insurance and Outcomes of Patients Requiring Biologic Therapies for Inflammatory Bowel Disease

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    Amir Rumman

    2017-01-01

    Full Text Available Background. Antitumor necrosis factor (anti-TNF therapy is a highly effective but costly treatment for inflammatory bowel disease (IBD. Methods. We conducted a retrospective cohort study of IBD patients who were prescribed anti-TNF therapy (2007–2014 in Ontario. We assessed if the insurance type was a predictor of timely access to anti-TNF therapy and nonroutine health utilization (emergency department visits and hospitalizations. Results. There were 268 patients with IBD who were prescribed anti-TNF therapy. Public drug coverage was associated with longer median wait times to first dose than private one (56 versus 35 days, P=0.002. After adjusting for confounders, publicly insured patients were less likely to receive timely access to anti-TNF therapy compared with those privately insured (adjusted hazard ratio, 0.66; 95% CI: 0.45–0.95. After adjustment for demographic and clinical characteristics, publicly funded subjects were more than 2-fold more likely to require hospitalization (incidence rate ratio [IRR], 2.30; 95% CI: 1.19–4.43 and ED visits (IRR 2.42; 95% CI: 1.44–4.08 related to IBD. Conclusions. IBD patients in Ontario with public drug coverage experienced greater delays in access to anti-TNF therapy than privately insured patients and have a higher rate of hospitalizations and ED visits related to IBD.

  17. Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering.

    Science.gov (United States)

    Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan

    2014-06-01

    Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Engineered particles demonstrate improved flow properties at elevated drug loadings for direct compression manufacturing.

    Science.gov (United States)

    Trementozzi, Andrea N; Leung, Cheuk-Yui; Osei-Yeboah, Frederick; Irdam, Erwin; Lin, Yiqing; MacPhee, J Michael; Boulas, Pierre; Karki, Shyam B; Zawaneh, Peter N

    2017-05-15

    Optimizing powder flow and compaction properties are critical for ensuring a robust tablet manufacturing process. The impact of flow and compaction properties of the active pharmaceutical ingredient (API) becomes progressively significant for higher drug load formulations, and for scaling up manufacturing processes. This study demonstrated that flow properties of a powder blend can be improved through API particle engineering, without critically impacting blend tabletability at elevated drug loadings. In studying a jet milled API (D 50 =24μm) and particle engineered wet milled API (D 50 =70μm and 90μm), flow functions of all API lots were similarly poor despite the vast difference in average particle size (ff c powder flow properties are directly correlated to particle size distribution. Upon adding excipients, however, clear trends in flow functions based on API particle size were observed. Wet milled API blends had a much improved flow function (ff c >10) compared with the jet milled API blends. Investigation of the compaction properties of both wet and jet milled powder blends also revealed that both jet and wet milled material produced robust tablets at the drug loadings used. The ability to practically demonstrate this uncommon observation that similarly poor flowing APIs can lead to a marked difference upon blending is important for pharmaceutical development. It is especially important in early phase development during API selection, and is advantageous particularly when material-sparing techniques are utilized. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Keiji Numata

    2013-01-01

    Full Text Available There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin, protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin. The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed.

  20. Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

    Science.gov (United States)

    Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2013-06-01

    In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

  1. Drug-Encoded Biomarkers for Monitoring Biological Therapies.

    Directory of Open Access Journals (Sweden)

    Desislava Tsoneva

    Full Text Available Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA and Staphylococcus sp. RLH1 (GusPlus, and the luciferase from Gaussia princeps (GLuc. The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml and GLuc (≥375 pg/ml. Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was substantially higher than that of GusPlus. This was attributed to a 3.2 fold and 16.2 fold longer half-life of GusA in the blood stream compared to GusPlus and GLuc respectively, thus a more sensitive monitor of virus replication than the other two enzymes. Due to the good correlation between enzymatic activity of expressed marker gene and virus titer, we conclude that the amount of the biomarker protein in the body fluid semiquantitatively represents the amount of virus in the infected tumors which was confirmed by low light imaging. We found GusA to be the most reliable biomarker for monitoring oncolytic virotherapy among the three tested markers.

  2. Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

    Science.gov (United States)

    Gonczi, Lorant; Kurti, Zsuzsanna; Rutka, Mariann; Vegh, Zsuzsanna; Farkas, Klaudia; Lovasz, Barbara D; Golovics, Petra A; Gecse, Krisztina B; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

    2017-08-08

    Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

  3. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy.

    Science.gov (United States)

    Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2015-09-24

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL 'opens' to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

  4. [Drugs dosing in intensive care unit during continuous renal replacement therapy].

    Science.gov (United States)

    Bourquin, Vincent; Ponte, Belén; Saudan, Patrick; Martin, Pierre-Yves

    2009-11-01

    Drug dosing in the intensive care unit can be challenging. Acute kidney injury (AKI) is a common complication of sepsis and a part of multiple organ dysfunction syndrome. Continuous renal replacement therapy (CRRT) is increasingly used as dialysis therapy in this critically ill population. Available data demonstrate that sepsis, AKI and different modalities of CRRT can profoundly change drugs pharmacokinetic. The severity of these changes depends on molecules characteristics (volume of distribution, plasma protein binding, molecular weight, plasma half-life, plasma clearance), patient itself (volemia, residual renal function, tissue perfusion, hepatic dysfunction) and modality of CRRT (diffusion, convection, adsorption). There are no available recommendations to adapt drug dosing in a given critically ill patient with a given modality of CRRT. It is necessary to fully understand the different methods of CRRT and drug pharmacokinetic to prescribe the appropriate dose and to avoid under or potentially toxic overdosing. Monitoring the plasma level of drug - when available - can establish a relation between the blood concentration and its effect; thus, facilitating drug dosing.

  5. Drug-Free Platelets Can Act as Seeds for Aggregate Formation During Antiplatelet Therapy

    Science.gov (United States)

    Hoefer, Thomas; Armstrong, Paul C.; Finsterbusch, Michaela; Chan, Melissa V.; Kirkby, Nicholas S.

    2015-01-01

    Objective— Reduced antiplatelet drug efficacy occurs in conditions of increased platelet turnover, associated with increased proportions of drug-free, that is, uninhibited, platelets. Here, we detail mechanisms by which drug-free platelets promote platelet aggregation in the face of standard antiplatelet therapy. Approach and Results— To model standard antiplatelet therapy, platelets were treated in vitro with aspirin, the P2Y12 receptor blocker prasugrel active metabolite, or aspirin plus prasugrel active metabolite. Different proportions of uninhibited platelets were then introduced. Light transmission aggregometry analysis demonstrated clear positive associations between proportions of drug-free platelets and percentage platelet aggregation in response to a range of platelet agonists. Using differential platelet labeling coupled with advanced flow cytometry and confocal imaging we found aggregates formed in mixtures of aspirin-inhibited platelets together with drug-free platelets were characterized by intermingled platelet populations. This distribution is in accordance with the ability of drug-free platelets to generate thromboxane A2 and so drive secondary platelet activation. Conversely, aggregates formed in mixtures of prasugrel active metabolite–inhibited or aspirin plus prasugrel active metabolite–inhibited platelets together with drug-free platelets were characterized by distinct cores of drug-free platelets. This distribution is consistent with the ability of drug-free platelets to respond to the secondary activator ADP. Conclusions— These experiments are the first to image the interactions of inhibited and uninhibited platelets in the formation of platelet aggregates. They demonstrate that a general population of platelets can contain subpopulations that respond strikingly differently to overall stimulation of the population and so act as the seed for platelet aggregation. PMID:26272940

  6. A green approach to dual-drug nanoformulations with targeting and synergistic effects for cancer therapy.

    Science.gov (United States)

    Wu, Shichao; Yang, Xiangrui; Lu, Yue; Fan, Zhongxiong; Li, Yang; Jiang, Yuan; Hou, Zhenqing

    2017-11-01

    Exploration of efficient dual-drug nanohybrids, particularly those with high drug loading, specific targeting property, and long-termed stability, is of highly importance in cancer therapy. A pH-driven coprecipitation was performed in the aqueous phase to obtain a dual-drug nanoformulation, composed of 10-hydroxycamptothecine (HCPT) nanoneedles integrated with an exterior thin layer of the methotrexate (MTX)-chitosan conjugate. The high stability of nanohybrids in water and the targeting property provided by the MTX ingredient function synergistically to the prolonged and sustained drug release property in tumor tissues and the increased cellular uptake. The cytotoxicity test illustrates that dual-drug nanoneedles possess the remarkable killing ability to HeLa cells with the combination index at 0.33 ± 0.07. After cellular internalization, the release of both drug ingredients results in an excellent anticancer activity in vivo with the minimized adverse side effects. Design of a green approach to the carrier-free, dual-drug nanoformulations enables to develop emerging drug delivery systems for cancer diagnosis and treatment.

  7. Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred

    2016-04-01

    A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  8. Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia

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    Philipp Koehler

    2012-01-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells.

  9. Cyclotides as grafting frameworks for protein engineering and drug design applications.

    Science.gov (United States)

    Poth, Aaron G; Chan, Lai Y; Craik, David J

    2013-09-01

    Cyclotides are a family of naturally occurring backbone-cyclized macrocyclic mini-proteins from plants that have a knotted trio of intramolecular disulfide bonds. Their structural features imbue cyclotides with extraordinary stability against degradation at elevated temperatures or in the presence of proteolytic enzymes. The plasticity of their intracysteine loop sequences is exemplified by the more than 250 natural cyclotides sequenced to date, and this tolerance to sequence variation, along with their diverse bioactivities, underpins the suitability of the cyclic cystine knot motif as a valuable drug design scaffold and research tool for protein engineering studies. Here, we review the recent literature on applications of cyclotides for the stabilization of peptide epitopes and related protein engineering studies. Possible future directions in this field are also described. Copyright © 2013 Wiley Periodicals, Inc.

  10. [Effects of drug cupping therapy on immune function in chronic asthmatic bronchitis patients during protracted period].

    Science.gov (United States)

    Zhang, Cai-qing; Liang, Tie-jun; Zhang, Wei

    2006-11-01

    To observe the clinical effect of drug cupping therapy (DCT, cupping therapy with pingchuan ointment made by the authors themselves in the cups) on chronic asthmatic bronchitis (CAB) during the protracted period, and explore its effect on immune function. Seventy-seven patients were randomly divided into two groups:the treated group (n=40) treated by orally taken Liuwei Dihuang Pill (LDP) and DCT and the control group (n=37) with LDP and common cupping therapy without drug in cups. The changes of T-lymphocyte subset, levels of interferon-gamma (IFN-gamma), interleukin (IL), immunoglobulin (Ig), complement 3 and 4 (C3 and C4) were detected before and after treatment. The total effective rate was higher in the treated group than that in the control group (90.0% vs. 59.5%, P < 0.01). The levels of CD4+, CD4+ /CD8+, IL-2, IFN-gamma, C3, C4, IgA, IgG and IgM increased, while the levels of IgE, IL-4, IL-10 and CD8+ decreased after treatment in both groups (P < 0.05 or P < 0.01), the improvements were better in the treated group than that in the control group (P < 0.05). DCT shows better curative effects than that of common cupping therapy without drug, it could improve the cellular and humoral immunity in CAB patients.

  11. Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

    Science.gov (United States)

    da Rocha, E L; Porto, L M; Rambo, C R

    2014-01-01

    Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

  12. Crystals of Serum Albumin for Use in Genetic Engineering and Rational Drug Design

    Science.gov (United States)

    Carter, Daniel C. (Inventor)

    1996-01-01

    Serum albumin crystal forms have been produced which exhibit superior x-ray diffraction quality. The crystals are produced from both recombinant and wild-type human serum albumin, canine, and baboon serum albumin and allow the performance of drug-binding studies as well as genetic engineering studies. The crystals are grown from solutions of polyethylene glycol or ammonium sulphate within prescribed limits during growth times from one to several weeks and include the following space groups: P2(sub 1), C2, P1.

  13. Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

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    Roberta Balansin Rigon

    2015-01-01

    Full Text Available Melanoma (MEL is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012 estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

  14. Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy.

    Science.gov (United States)

    Swathy, Babu; Banerjee, Moinak

    2017-05-01

    The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects. We re-examine the context of epigenetics in disease pathogenesis and antipsychotic drug therapy in SCZ to understand how much of these observations act as real indicators of the disease or therapeutic response. We propose that epigenetic viewpoint in SCZ needs to be critically examined under the genetic, epigenetic and pharmacoepigenetic background.

  15. Nuclear medicine: proof of principle for targeted drugs in diagnosis and therapy.

    Science.gov (United States)

    Leitha, Thomas

    2009-01-01

    Delivering a drug to a specific target in the body is comparable to the "magic bullet principle" applied in Nuclear Medicine. If clinical medicine today found treatment options by targeting specific receptors, proteins or enzymes by "small-molecule drugs" it utilizes concepts that have been initially described by Nobel Laureate George von Hevesy as "tracer principle". This article is going to show that molecular imaging probes in Nuclear Medicine can be regarded as proof of principle of many of recent trends in diagnosis and therapy and offers exciting opportunities for further developments. Radioiodine therapy of benign and malignant thyroid disease has been established in Nuclear Medicine over six decades ago and is a fine example for using the same highly specific probe for diagnosis and treatment of a given disease. The use of radio labeled monoclonal antibodies against surface receptors of tumor cells (e.g. CEA) dominated diagnostic Nuclear Medicine in the eighties and sees a recent revival in lymphoma treatment radioimmunotherapy. Finally Nuclear Medicine has shown that it may advance drug development by visualizing its biodistribution and site of action. On the other hand some drugs like somatostatin analogues have been reinvented as diagnostic and therapeutic probes over a decade after their initial introduction as therapeutics. Molecular Imaging and targeted therapy are merging and potentiate their individual strength. Nuclear Medicine has ample experience in applying Molecular Imaging in clinical research and practice and has a bright future in this exciting field.

  16. Regional Lymphotropic Therapy in Combination with Low Level Laser Therapy for Treating Multi-Drug-Resistant Tuberculosis

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    Oksana Dogorova

    2016-03-01

    Full Text Available With the growing incidence of Multi-Drug-Resistant Tuberculosis (MDR-TB in newly identified patients, novel multimodality treatment methods are needed, aimed at reducing the time to sputum conversion and cavity healing, which would be applicable in MDR cases. Our experimental treatment consisted of the following: 1 chemotherapy based on the drug sensitivity profile, 2 local laser irradiation therapy for 25 days, and lymphotropic administration of isoniazid (to subcutaneous tissue in alternating locations: underarm area; fifth intercostal space along the sterna border; subclavian area where the first rib meets the sternum in a daily dose of 10mg/kg 5 times a week. This treatment was significantly more effective in newly detected destructive MDR-TB versus the standard Category IV regimen for MDR-TB in terms of reduced time for sputum culture conversion and cavity healing, estimated to be 6 months after initiation of treatment.

  17. Decreased tacrolimus plasma concentrations during HCV therapy: a drug-drug interaction or is there an alternative explanation?

    Science.gov (United States)

    Smolders, E J; Pape, S; de Kanter, C T M M; van den Berg, A P; Drenth, J P H; Burger, D M

    2017-03-01

    Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment. We hypothesise that decreased plasma concentrations were not caused by a DDI but were an indirect result of the clearance of the HCV infection. During chronic HCV infection, pro-inflammatory cytokines may inhibit cytochrome P450 (CYP) enzymes, which are primarily responsible for tacrolimus metabolism. If this is true, then with clearance of the virus the activity of these enzymes will normalise and tacrolimus metabolism will increase. These changes were clinically relevant because the tacrolimus dosage needed to be adjusted. Therefore, physicians should be aware that CYP substrates with narrow therapeutic ranges might require dose adaption during HCV therapy with DAAs. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  18. Engineering of layered, lipid-encapsulated drug nanoparticles through spray-drying.

    Science.gov (United States)

    Sapra, Mahak; Mayya, Y S; Venkataraman, Chandra

    2017-06-01

    Drug-containing nanoparticles have been synthesized through the spray-drying of submicron droplet aerosols by using matrix materials such as lipids and biopolymers. Understanding layer formation in composite nanoparticles is essential for the appropriate engineering of particle substructures. The present study developed a droplet-shrinkage model for predicting the solid-phase formation of two non-volatile solutes-stearic acid lipid and a set of drugs, by considering molecular volume and solubility. Nanoparticle formation was simulated to define the parameter space of material properties and process conditions for the formation of a layered structure with the preferential accumulation of the lipid in the outer layer. Moreover, lipid-drug demarcation diagrams representing a set of critical values of ratios of solute properties at which the two solutes precipitate simultaneously were developed. The model was validated through the preparation of stearic acid-isoniazid nanoparticles under controlled processing conditions. The developed model can guide the selection of solvents, lipids, and processing conditions such that drug loading and lipid encapsulation in composite nanoparticles are optimized. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Towards iconic language for patient records, drug monographs, guidelines and medical search engines.

    Science.gov (United States)

    Lamy, Jean-Baptiste; Duclos, Catherine; Hamek, Saliha; Beuscart-Zéphir, Marie-Catherine; Kerdelhué, Gaetan; Darmoni, Stefan; Favre, Madeleine; Falcoff, Hector; Simon, Christian; Pereira, Suzanne; Serrot, Elisabeth; Mitouard, Thierry; Hardouin, Etienne; Kergosien, Yannick; Venot, Alain

    2010-01-01

    Practicing physicians have limited time for consulting medical knowledge and records. We have previously shown that using icons instead of text to present drug monographs may allow contraindications and adverse effects to be identified more rapidly and more accurately. These findings were based on the use of an iconic language designed for drug knowledge, providing icons for many medical concepts, including diseases, antecedents, drug classes and tests. In this paper, we describe a new project aimed at extending this iconic language, and exploring the possible applications of these icons in medicine. Based on evaluators' comments, focus groups of physicians and opinions of academic, industrial and associative partners, we propose iconic applications related to patient records, for example summarizing patient conditions, searching for specific clinical documents and helping to code structured data. Other applications involve the presentation of clinical practice guidelines and improving the interface of medical search engines. These new applications could use the same iconic language that was designed for drug knowledge, with a few additional items that respect the logic of the language.

  20. Microfabricated Engineered Particle Systems for Respiratory Drug Delivery and Other Pharmaceutical Applications

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    Andres Garcia

    2012-01-01

    Full Text Available Particle Replication in Non-Wetting Templates (PRINT® is a platform particle drug delivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry have been used to enhance systemic particle distribution properties. In addition, we introduce the application of PRINT technology towards respiratory drug delivery, a particular interest due to the pharmaceutical need for increased control over dry powder characteristics to improve drug delivery and therapeutic indices. To this end, we have produced dry powder particles with micro- and nanoscale geometric features and composed of small molecule and protein therapeutics. Aerosols generated from these particles show attractive properties for efficient pulmonary delivery and differential respiratory deposition characteristics based on particle geometry. This work highlights the advantages of adopting proven microfabrication techniques in achieving unprecedented control over particle geometric design for drug delivery.

  1. Human engineered heart tissue as a model system for drug testing.

    Science.gov (United States)

    Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

    2016-01-15

    Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Flow cytometric determination of osmotic behaviour of animal erythrocytes toward their engineering for drug delivery

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    Kostić Ivana T.

    2015-01-01

    Full Text Available Despite the fact that the methods based on the osmotic properties of the cells are the most widely used for loading of drugs in human and animal erythrocytes, data related to the osmotic properties of erythrocytes derived from animal blood are scarce. This work was performed with an aim to investigate the possibility of use the flow cytometry as a tool for determination the osmotic behaviour of porcine and bovine erythrocytes, and thus facilitate the engineering of erythrocytes from animal blood to be drug carriers. The method of flow cytometry successfully provided the information about bovine and porcine erythrocyte osmotic fragility, and made the initial steps in assessment of erythrocyte shape in a large number of erythrocytes. Although this method is not able to confirm the swelling of pig erythrocytes, it indicated to the differences in pig erythrocytes that had basic hematological parameters inside and outside the reference values. In order to apply/use the porcine and bovine erythrocytes as drug carriers, the method of flow cytometry, confirming the presence of osmotically different fractions of red blood cells, indicated that various amounts of the encapsulated drug in porcine and bovine erythrocytes can be expected.

  3. Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

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    Haeberle Anne

    2012-09-01

    Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.

  4. Clinical relevancy and risks of potential drug-drug interactions in intensive therapy.

    Science.gov (United States)

    Rodrigues, Aline Teotonio; Stahlschmidt, Rebeca; Granja, Silvia; Falcão, Antonio Luis Eiras; Moriel, Patricia; Mazzola, Priscila Gava

    2015-09-01

    Evaluate the potential Drug-Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®. Prospective study (January-December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient. During the study 1844 pDDIs were identified and distributed in 405 pairs (medication A × medication B combination). There was an average of 5.00 ± 5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to "avoid concomitant use" or "suspension of medication", while 306 had as recommendation "continuous and adequate monitoring". The high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management.

  5. A short history of anti-rheumatic therapy. I. An introduction on traditional and drug treatments

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    G. Pasero

    2011-06-01

    Full Text Available The origins of anti-rheumatic therapy are very old and mainly related to the use of traditional, sometimes extravagant, treatments, as a part of folk medicine. Spa therapy has long been used for the treatment of rheumatic diseases, as well as, in later times, physical treatments, including electrotherapy. Drug treatment has developed beginning from substances of vegetable origin, such as willow and colchicum extracts. Then it has been spread out through the chemical synthesis of compounds with specific action and therefore more effective, owing to the great development of pharmaceutical industry.

  6. Reconstituted viral envelopes--'Trojan horses' for drug delivery and gene therapy?

    Science.gov (United States)

    Blumenthal, R; Loyter, A

    1991-02-01

    Reconstituted viral envelopes (RVEs) are formed by solubilizing intact virus in detergent and reassembling the envelope on removal of detergent. RVEs can be formed in the presence of agents that become encapsulated and can then be utilized in vitro and in vivo for drug delivery, cell destruction, transfer of membrane components, and as vectors for genetic engineering. The problems with biotechnological applications of RVEs and possible strategies for overcoming them are discussed in this article.

  7. Microsponge based drug delivery system for augmented gastroparesis therapy: Formulation development and evaluation

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    Riyaz Ali M. Osmani

    2015-10-01

    Full Text Available The intention behind the present work was to develop a microsponge based novel dosage form for sustained delivery of domperidone. Quasi-emulsion solvent diffusion method was employed using Eudragit RS-100 with various drug–polymer ratios for the preparation of microsponges. For optimization purposes, several factors which affect microparticles' physical properties were investigated. Characterization techniques followed for the formed microsponges were DSC, FTIR, SEM, XRD and particle size analysis, along with morphology, drug loading and in vitro drug release. It was found that there were no chemical interactions between drugs and polymers used as per DSC and FTIR results. The drug–polymer ratio showed remarkable impact on drug content, encapsulation efficiency and particle size. SEM micrographs revealed that microsponges were spherical in shape with porous surface, and had 104 ± 0.22 µm mean particle size. The microsponges were then loaded in capsules followed by in vitro drug release study; which depicted that microsponges with drug–polymer ratio of 1:2 were more proficient to give extended drug release of 76.38% at the end of 8 h, superior in contrast to conventional marketed formulation Domstal®, which got exhausted incredibly earlier by releasing 82.57% drug at the end of ½ h only. Hence, the developed microsponge based formulation of domperidone would be an expectant, promising substitute to conventional therapy of gastroparesis, emesis and alike gastric ailments.

  8. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    Science.gov (United States)

    2011-01-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies. PMID:21995320

  9. Advances in research and development of new drugs for antiviral therapy for chronic hepatitis B

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    GAO Yanhang

    2016-11-01

    Full Text Available Chronic hepatitis B virus (HBV infection is one of the major disease burdens worldwide. At present, the antiviral therapy for hepatitis B includes interferons and nucleos(tide analogues. Current therapeutic regimens based on these drugs cannot significantly increase the proportion of patients with functional cure. With a better understanding of HBV replication cycle and specific virus-host cell interactions, this article summarizes and reviews the advances in the research and development of new drugs for HBV with a focus on different action targets during the above processes.

  10. Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

    Science.gov (United States)

    Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

    2010-07-01

    The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

  11. Stimuli responsive drug delivery systems based on nano-graphene for cancer therapy.

    Science.gov (United States)

    Yang, Kai; Feng, Liangzhu; Liu, Zhuang

    2016-10-01

    Nano-graphene as a class of two-dimensional sp2 carbon nanomaterial has attracted tremendous attentions in various fields in the past decade. Utilizing its unique physical and chemical properties, nano-graphene has also shown great promises in the area of biomedicine, for application in biosensing, imaging and therapy. In particular, with all atoms exposed on its surface, nano-graphene exhibits ultra-high surface area available for efficient binding/loading of various biomolecules of interests, and has been widely used as multifunctional nano-carriers for drug and gene delivery. In this review article, we will summarize the recent advances in the development of nano-graphene as stimuli-responsive nano-carriers for drug delivery, as well as the applications of these smart systems for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. APPLICABILITY OF THE NON STEROID ANTIINFLAMMATORY DRUGS IN FEVER THERAPY OF CHILDREN

    Directory of Open Access Journals (Sweden)

    O.A. Mubarakshina

    2008-01-01

    Full Text Available The non steroid anti-inflammatory drugs are widely applied in the pediatric practices for the fever therapy among children. While choosing the medications from this group to prescribe them to the children, it is essential to get guided towards the highly efficient medications with the least risk of the side effects. Only Paracetamol and ibuprofen are fully compliant with this requirement. They are officially recommended by who as the anti febrile medications for use in pediatrics. In the given article, the author reviews the advantages of ibuprofen over to Paracetamol based on the data from the foreign randomized research. She pays certain attention to the safety issues during the ibuprofen based treatment and to the opportunities of the combined Paracetamol and ibuprofen based therapy.Key words: fever, treatment, non steroid anti-inflammatory drugs, children.

  13. Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?

    Science.gov (United States)

    Thillai, Kiruthikah; Ross, Paul; Sarker, Debashis

    2016-01-01

    Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC. PMID:26909132

  14. The impact of epigenomics on future drug design and new therapies.

    Science.gov (United States)

    Hamm, Christopher A; Costa, Fabricio F

    2011-07-01

    The future of drug design and the development of new therapeutics will rely on our ability to unravel the complexities of the epigenome in normal and disease states. Proper epigenetic regulation is essential for normal differentiation in embryogenesis and development. Conversely, abnormal epigenetic regulation is a feature of complex diseases, including cancer, diabetes, heart disease and other pathologies. Epigenetic therapies hold promise for a wide range of biological applications, from cancer treatment to the establishment of induced pluripotent stem cells. The creation of more specific and effective epigenetic therapies, however, requires a more complete understanding of epigenomic landscapes. Here, we give a historical overview of the epigenomics field and how epigenetic modifications can affect embryo development and disease etiology. We also discuss the impact of current and future epigenetic drugs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Immune regulation of therapy-resistant niches: emerging targets for improving anticancer drug responses.

    Science.gov (United States)

    Jinushi, Masahisa

    2014-09-01

    Emerging evidence has unveiled a critical role for immunological parameters in predicting tumor prognosis and clinical responses to anticancer therapeutics. On the other hand, responsiveness to anticancer drugs greatly modifies the repertoires, phenotypes, and immunogenicity of tumor-infiltrating immune cells, serving as a critical factor to regulate tumorigenic activities and the emergence of therapy-resistant phenotypes. Tumor-associated immune functions are influenced by distinct or overlapping sets of therapeutic modalities, such as cytotoxic chemotherapy, radiotherapy, or molecular-targeted therapy, and various anticancer modalities have unique properties to influence the mode of cross-talk between tumor cells and immune cells in tumor microenvironments. Thus, it is critical to understand precise molecular machineries whereby each anticancer strategy has a distinct or overlapping role in regulating the dynamism of reciprocal communication between tumor and immune cells in tumor microenvironments. Such an understanding will open new therapeutic opportunities by harnessing the immune system to overcome resistance to conventional anticancer drugs.

  16. Update zum Therapeutic Drug Monitoring und zu pharmakogenetischen Untersuchungen zur Optimierung der Therapie mit Psychopharmaka

    OpenAIRE

    Rentsch, Katharina M.

    2017-01-01

    Das Therapeutic Drug Monitoring von Psychopharmaka wird in zahlreichen Laboratorien immer häufiger durchgeführt, ebenso wie pharmakogenetische Untersuchungen. In diesem Übersichtsartikel wurde die dazugehörige Literatur aus den Jahren 2011 und 2012 zusammengefasst. Die Guidelines der AGNP enthalten alle wichtigen Informationen, die notwendig sind, um Konzentrationen von Psychopharmaka richtig zu interpretieren. Die Bestimmung von Serotonin im Urin könnte ein Marker zur Beurteilung des Therapi...

  17. Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation

    DEFF Research Database (Denmark)

    Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise

    2012-01-01

    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...

  18. A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

    Science.gov (United States)

    Collatz, Ansel; Johnston, Samantha C; Staines, Donald R; Marshall-Gradisnik, Sonya M

    2016-06-01

    The pathogenesis of chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is complex and remains poorly understood. Evidence regarding the use of drug therapies in CFS/ME is currently limited and conflicting. The aim of this systematic review was to examine the existing evidence on the efficacy of drug therapies and determine whether any can be recommended for patients with CFS/ME. MEDLINE, EMBASE, and PubMed databases were searched from the start of their records to March 2016 to identify relevant studies. Randomized controlled trials focusing solely on drug therapy to alleviate and/or eliminate chronic fatigue symptoms were included in the review. Any trials that considered graded exercise therapy, cognitive behavior therapy, adaptive pacing, or any other nonpharmaceutical treatment plans were excluded. The inclusion criteria were examined to ensure that study participants met specific CFS/ME diagnostic criteria. Study size, intervention, and end point outcome domains were summarized. A total of 1039 studies were identified with the search terms; 26 studies met all the criteria and were considered suitable for review. Three different diagnostic criteria were identified: the Holmes criteria, International Consensus Criteria, and the Fukuda criteria. Primary outcomes were identified as fatigue, pain, mood, neurocognitive dysfunction and sleep quality, symptom severity, functional status, and well-being or overall health status. Twenty pharmaceutical classes were trialed. Ten medications were shown to be slightly to moderately effective in their respective study groups (P treatment can be recommended. The unknown etiology of CFS/ME, and complications arising from its heterogeneous nature, contributes to the lack of clear evidence for pharmaceutical interventions. However, patients report using a large number and variety of medications. This finding highlights the need for trials with clearly defined CFS/ME cohorts. Trials based on more specific criteria

  19. New drug therapies for the treatment of overweight and obese patients.

    Science.gov (United States)

    Mahgerefteh, Babak; Vigue, Michael; Freestone, Zachary; Silver, Scott; Nguyen, Quang

    2013-09-01

    Obesity is a serious and costly disease that is growing in epidemic proportions. Obesity-related hospitalizations have nearly tripled from 1996 to 2009. If the current trend in the growth of obesity continues, the total healthcare costs attributable to obesity could reach $861 billion to $957 billion by 2030. The American Medical Association has officially recognized obesity as a disease. Obesity is a public health crisis affecting approximately more than 33% of Americans and costing the healthcare system more than $190 billion annually. To review the 2 new drugs that were recently approved by the US Food and Drug Administration (FDA) for the treatment of obesity, lorcaserin HCl (Belviq) and phentermine/topiramate (Qsymia) and their potential impact on the treatment of obese patients. Lifestyle modification is the first and mainstay treatment for obesity. Antiobesity drugs are indicated as adjuncts to a healthy, low-fat, low-calorie diet and an exercise plan. Currently, 4 drugs are approved by the FDA for the treatment of obesity, 2 of which were approved after June 2012. These 2 drugs, Belviq and Qsymia, have added new tools for the treatment of obesity. In addition to reducing body mass index, these drugs have been shown to reduce hemoglobin A1c levels in patients with diabetes and blood pressure levels in patients with hypertension, as well as to decrease lipid levels in patients with hyperlipidemia. This article reviews the drugs' mechanisms of action, evaluates landmark clinical studies leading to the FDA approval of the 2 drugs, their common side effects, and the benefits these new drugs can provide toward the management of the obesity epidemic that are different from other medications currently available. The weight loss seen in patients who are using the 2 new medications has been shown to further improve other cardiometabolic health parameters, including blood pressure, blood glucose levels, and serum lipid levels. Based on clinical trials evidence, it is

  20. GENERALIZED ANALYSIS OF THE RESULTS OF GENETICALLY ENGINEERED BIOLOGICAL THERAPY: SEARCHES FOR NEW PATTERNS

    Directory of Open Access Journals (Sweden)

    Yakov Aleksandrovich Sigidin

    2013-01-01

    Full Text Available The clinical analysis of the results of genetically engineered biological therapy identifies a number of patterns of the mechanism of action of this therapy and the pathogenetic features of rheumatic diseases. The results of using genetically engineered biological agents (GEBA having different mechanisms of action allow one to identify categories of rheumatoid arthritis patients with different pathogenetic features. Various cytokines can play a major pathogenic role in a clinically similar inflammatory process. The therapeutic effect of tumor necrosis factor-α (TNF-α inhibitors exhibits the predominance of their nonspecific anti-inflammatory activity over the immunosuppressive one. Contrary to the previous ideas of cytokine hierarchy, TNF-α neutralization does not block the effects of interleukin 6 (IL-6. Anti-B-cell therapy is most effective in patients with significant autoimmune disorders; a contrary pattern is observed when TNF-α inhibitors are used. TNF-α is very important in the development of an inflammatory process in ankylosing spondylitis (AS while the role of IL6 is insignificant. Autoimmune disorders in AS are not marked; whereby predominantly immunotropic GEBAs (rituximab and abatacept are ineffective in this disease. The blocking of a biological reaction to inflammation cannot coincide with the suppression of the inflammatory process proper.

  1. Renal denervation, adjusted drugs, or combined therapy for resistant hypertension: A meta-regression.

    Science.gov (United States)

    Qi, Xiao-Yu; Cheng, Bin; Li, Ying-Li; Wang, Yue-Feng

    2016-07-01

    The objective of this study is to systematically evaluate the efficacy of renal denervation (RD), adjusted drugs, or combined therapy for resistant hypertension (RH) through a systematic review and meta-analysis of controlled studies.Publications were comprehensively searched. Studies that investigated the effects of RD and/or adjusted drugs in lowering blood pressure (BP) were included. After quality assessment and data extraction, subgroup analyzes were first performed according to blinding method. Meta-regression and inverted funnel plots were also conducted.A total of 13 studies containing 1604 RH patients were included. Compared with control, the meta-analysis showed that RD significantly reduced office-based BP and ambulatory BP in 6 months in the unblinded studies, while no significant difference was found in the blinded studies. Meta-regression demonstrated the significant influence of blinding method on BP reduction, and further analysis revealed a significant BP reduction compared with baseline even in the control arm of blinded studies. RD had similar effects compared with adjusted drugs, and combined therapy seemed to further reduce the level of BP.The efficacy of RD was different between blinded and unblinded studies, and our data revealed a significant BP-lowering effect in the control arm of blinded studies, which was helpful to explain this finding. Furthermore, RD seemed to be equivalent to adjusted drugs, and also we suggested a potential advantage of combined therapy of RD and adjusted drugs compared with monotherapy for RH. However, more studies are warranted to better address the issue.

  2. Improvement of paracellular transport in the Caco-2 drug screening model using protein-engineered substrates.

    Science.gov (United States)

    DiMarco, Rebecca L; Hunt, Daniel R; Dewi, Ruby E; Heilshorn, Sarah C

    2017-06-01

    The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe underprediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport. Specifically, we use a biomimetic engineered extracellular matrix (eECM) that contains modular protein domains derived from two ECM proteins found in the small intestine, fibronectin and elastin. This eECM allows us to independently tune the density of cell-adhesive RGD ligands presented to Caco-2 cells as well as the mechanical stiffness of the eECM. We observe that lower amounts of RGD ligand presentation as well as decreased matrix stiffness results in Caco-2 morphologies that more closely resemble primary small intestinal epithelial cells than Caco-2 cells cultured on collagen. Additionally, these matrices result in Caco-2 monolayers with decreased recruitment of actin to the apical junctional complex and increased expression of claudin-2, a tight junction protein associated with higher paracellular permeability that is highly expressed throughout the small intestine. Consistent with these morphological differences, drugs known to be paracellularly transported in vivo exhibited significantly improved transport rates in this modified Caco-2 model. As expected, permeability of transcellularly transported drugs remained unaffected. Thus, we have demonstrated a method of improving the physiological accuracy of the Caco-2 assay that could be readily adopted by

  3. Individualization of anticancer therapy; molecular targets of novel drugs in oncology

    Directory of Open Access Journals (Sweden)

    Katarzyna Regulska

    2012-11-01

    Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology. 

  4. Mucoadhesive polyacrylamide nanogel as a potential hydrophobic drug carrier for intravesical bladder cancer therapy.

    Science.gov (United States)

    Lu, Shengjie; Neoh, Koon Gee; Kang, En-Tang; Mahendran, Ratha; Chiong, Edmund

    2015-05-25

    In this paper, amine-functionalized polyacrylamide nanogels (PAm-NH2) loaded with docetaxel (DTX) were evaluated as a mucoadhesive and sustained intravesical drug delivery (IDD) system for potential bladder cancer therapy. Nanogels have not been applied for such therapy before. The mucoadhesiveness of the PAm-NH2 nanogels, which is a critical factor for IDD application, was investigated using the mucin-particle method and by analyzing the direct attachment of the PAm-NH2 nanogels onto the luminal surface of porcine urinary bladder. DTX, as a model hydrophobic drug, was successfully loaded into hydrophilic PAm-NH2 nanogels with high loading efficiency (>90%), and sustained release of DTX from the nanogels over 9 days in artificial urine was achieved. The nanogels were also taken in by bladder cancer cells in a concentration-dependent manner. The efficiency of the DTX-loaded nanogels in killing UMUC3 and T24 bladder cancer cells was determined to be equivalent to free DTX, and the morphology of the bladder urothelium was not adversely altered by the PAm-NH2 nanogels. These findings indicate that such mucoadhesive nanogels are potentially a promising candidate for intravesical delivery of hydrophobic drugs in bladder cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  6. Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

    Directory of Open Access Journals (Sweden)

    Nathan W Kopper

    2008-10-01

    Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

  7. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    Science.gov (United States)

    Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

    2015-12-01

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial's manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell-biomaterial and cell- cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

  8. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Guarino, Vincenzo, E-mail: vguarino@unina.it; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi [Institute for Polymers, Composites and Biomaterials, Department of Chemical Sciences & Materials Technology, National Research Council of Italy, V.le Kennedy 54, Naples (Italy)

    2015-12-17

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

  9. A controlled evaluation of family behavior therapy in concurrent child neglect and drug abuse.

    Science.gov (United States)

    Donohue, Brad; Azrin, Nathan H; Bradshaw, Kelsey; Van Hasselt, Vincent B; Cross, Chad L; Urgelles, Jessica; Romero, Valerie; Hill, Heather H; Allen, Daniel N

    2014-08-01

    Approximately 50% of child protective service (CPS) referrals abuse drugs; yet, existing treatment studies in this population have been limited to case examinations. Therefore, a family-based behavioral therapy was evaluated in mothers referred from CPS for child neglect and drug abuse utilizing a controlled experimental design. Seventy-two mothers evidencing drug abuse or dependence and child neglect were randomly assigned to family behavior therapy (FBT) or treatment as usual (TAU). Participants were assessed at baseline, 6 months, and 10 months postrandomization. As hypothesized, intent-to-treat repeated measures analyses revealed mothers referred for child neglect not due to their children being exposed to illicit drugs demonstrated better outcomes in child maltreatment potential from baseline to 6- and 10-month postrandomization assessments when assigned to FBT, as compared with TAU mothers and FBT mothers who were referred due to child drug exposure. Similar results occurred for hard drug use from baseline to 6 and 10 months postrandomization. However, TAU mothers referred due to child drug exposure were also found to decrease their hard drug use more than TAU mothers of non-drug-exposed children and FBT mothers of drug-exposed children at 6 and 10 months postrandomization. Although effect sizes for mothers assigned to FBT were slightly larger for marijuana use than TAU (medium vs. large), these differences were not statistically significant. Specific to secondary outcomes, mothers in FBT, relative to TAU, increased time employed from baseline to 6 and 10 months postrandomization. Mothers in FBT, compared to TAU, also decreased HIV risk from baseline to 6 months postrandomization. There were no differences in outcome between FBT and TAU for number of days children were in CPS custody and alcohol intoxication, although FBT mothers demonstrated marginal decreases (p = .058) in incarceration from baseline to 6 months postrandomization relative to TAU mothers

  10. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

    Science.gov (United States)

    Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

    2016-03-11

    Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  11. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

    Directory of Open Access Journals (Sweden)

    Giovana Maria Fioramonti Calixto

    2016-03-01

    Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  12. Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

    Science.gov (United States)

    Lin, Tai-Chi; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Liu, Jorn-Hon; Woung, Lin-Chung; Tsai, Ching-Yao; Chen, Shih-Jen; Chen, Yan-Ting; Hsu, Chih-Chien

    2015-11-01

    Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration. Copyright © 2015. Published by Elsevier Taiwan.

  13. Advances in antibody-drug conjugates: A new era of targeted cancer therapy.

    Science.gov (United States)

    Sau, Samaresh; Alsaab, Hashem O; Kashaw, Sushil Kumar; Tatiparti, Katyayani; Iyer, Arun K

    2017-10-01

    Antibody-drug conjugates (ADCs), a potent class of anticancer therapeutics, comprise a high-affinity antibody (Ab) and cytotoxic payload coupled via a suitable linker for selective tumor cell killing. In the initial phase of their development, two ADCs, Mylotarg(®), and Adcetris(®) were approved by the US Food and Drug Administration (FDA) for treating hematological cancer, but the real breakthrough came with the discovery of the breast cancer-targeting ADC, Kadcyla(®). With advances in bioengineering, linker chemistry, and potent cytotoxic payload, ADC technology has become a more powerful tool for targeted cancer therapy. In addition, ADCs with improved safety using humanized Abs with a unified 'drug:antibody ratio' (DAR) have been achieved. Concomitantly, there has been a significant increase in the number of clinical trials with anticancer ADCs with high translation potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Artificial cell microencapsulated stem cells in regenerative medicine, tissue engineering and cell therapy.

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas Ming Swi

    2010-01-01

    Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity oftransdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo.

  15. Artificial Cell Microencapsulated Stem Cells in Regenerative Medicine, Tissue Engineering and Cell Therapy

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas Ming Swi

    2012-01-01

    Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity of transdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo. PMID:20384219

  16. Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice.

    Science.gov (United States)

    Ma, Hongge; Qiao, Shupei; Wang, Zeli; Geng, Shuai; Zhao, Yufang; Hou, Xiaolu; Tian, Weiming; Chen, Xiongbiao; Yao, Lifen

    2017-05-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses. Copyright © 2017 the American Physiological Society.

  17. Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Ranu A., E-mail: ranu.dutta16@gmail.com [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); NanoeRA medicare Private Limited, Uttar Pradesh (India); Sharma, Prashant K. [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); Indian School of Mines, Dhanbad (India); Tiwari, Vandana [Department of Pathology, KGMU, Lucknow (India); Tiwari, Vivek; Patel, Anant B. [Centre for Cellular and Molecular Biology, Hyderabad (India); Pandey, Ravindra [Department of Physics, Michigan Technological University, Michigan 49931-1295 (United States); Pandey, Avinash C. [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); NanoeRA medicare Private Limited, Uttar Pradesh (India); Bundelkhand University, Jhansi (India)

    2014-01-13

    The engineering of the Gadolinium based nanostructures have been demonstrated in this paper. Nanostructures of α-Gd{sub 2}S{sub 3} exhibit a unique transition between ferromagnetic state and paramagnetic state of the system. It was demonstrated that their properties could be tuned for a wide range of applications ranging from hyperthermia to Magnetic Resonance Imaging, owing to their magnetic moments and large relaxivities. Metallic Gd nanoparticles obtained by reduction method were employed for cancer imaging in mice. The Gd nanoparticles were coated with Curcumin and their biomedical implications in the field of simultaneous diagnosis and therapy of cancer and related diseases has been discussed.

  18. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

    Science.gov (United States)

    Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

    2017-04-01

    A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe3O4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which 60% of DOX was released at pH 5.4 and 10% was released at pH 7.4. In contrast, 90% CPT-11 was released at pH 5.4 and 70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy.

  19. Drug therapy for symptoms associated with anxiety in adult palliative care patients.

    Science.gov (United States)

    Salt, Susan; Mulvaney, Caroline A; Preston, Nancy J

    2017-05-18

    This is an update of a Cochrane Review first published in 2004 (Issue 1) and previously updated in 2012 (Issue 10). Anxiety is common in palliative care patients. It can be a natural response to the complex uncertainty of having a life-limiting illness or impending death, but it may represent a clinically significant issue in its own right. To assess the effectiveness of drug therapy for treating symptoms of anxiety in adults with a progressive life-limiting illness who are thought to be in their last year of life. We ran the searches for this update to May 2016. We searched the CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), PsychLIT (Silver Platter) and PsycINFO (Ovid). We searched seven trials registers and seven pharmaceutical industry trials registers. We handsearched the conference abstracts of the European Association of Palliative Care. Randomised controlled trials which examined the effect of drug therapy for the treatment of symptoms of anxiety in adult palliative care patients, that is, people with a known progressive life-limiting illness that is no longer responsive to curative treatment, including advanced heart, respiratory and neurological diseases (including dementia). Comparator treatments included placebo; another drug therapy or different dose schedule; or a non-drug intervention such as counselling, cognitive behaviour therapies or relaxation therapies. Two review authors independently screened titles and abstracts to identify potentially relevant papers for inclusion in the review. We sought full-text reports for all papers retained at this stage and two reviews authors independently assessed these for inclusion in the review. We planned to assess risk of bias and extract data including information on adverse events. We planned to assess the evidence using GRADE and to create a 'Summary of findings' table. In this update, we identified 707 potentially relevant papers and of these we sought the full-text reports of 10 papers. On

  20. Management of HIV/AIDS in older patients–drug/drug interactions and adherence to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Burgess MJ

    2015-10-01

    Full Text Available Mary J Burgess,1 John D Zeuli,2 Mary J Kasten31Division of Infectious Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Department of Pharmacy, Mayo Clinic, Rochester, MN, USA; 3Divisions of General Internal Medicine and Infectious Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Patients with human immunodeficiency virus (HIV are living longer with their disease, as HIV has become a chronic illness managed with combination antiretroviral therapy (cART. This has led to an increasing number of patients greater than 50 years old living successfully with HIV. As the number of older adults with HIV has increased, there are special considerations for the management of HIV. Older adults with HIV must be monitored for drug side effects and toxicities. Their other non-HIV comorbidities should also be considered when choosing a cART regimen. Older adults with HIV have unique issues related to medication compliance. They are more likely than the younger HIV patients to have vision loss, cognitive impairment, and polypharmacy. They may have lower expectations of their overall health status. Depression and financial concerns, especially if they are on a fixed income, may also contribute to noncompliance in the aging HIV population.Keywords: HIV, aging population, management issues, drug interactions, medication adherence

  1. Literature-based analysis on relationship of symptoms, drugs and therapies in treatment of intestinal diseases.

    Science.gov (United States)

    Gao, Luan; Wang, Jian; Li, Fenggang; Deng, Yong; Gao, Sihua

    2014-02-01

    To evaluate clinical articles published in the past 30 years using the Traditional Chinese Medicine (TCM) theory of the lung being connected with large intestine to treat intestinal diseases. We also analyzed the relationship between symptoms, drugs and therapies with data-excavating technology to aid management. After retrieving relevant clinical articles, we set up a database, used Microsoft Structured Query Language Server 2005 Analysis Services as a data-excavating tool, and applied the association rule to study the relationship between the symptoms, drugs and therapies of intestinal diseases. The key symptoms of dyschesia, constipation, abdominal fullness, fatigue and pale tongue could be treated with Kuxingren (Semen Armeniacae Amarum), Huangqi (Radix Astragali Mongolici) and Gualou (Fructus et Semen Trichosanthis) to invigorate Qi and moisten the intestine. Among these agents, Kuxingren (Semen Armeniacae Amarum) was used most frequently. Clearing Fu-organs was the most prevalent therapy for abdominal fullness, dyschesia, constipation and red tongue. Clearing Fu-organs could be achieved with Kuxingren (Semen Armeniacae Amarum) and Gua-lou (Fructus et Semen Trichosanthis), whereas Qi could be invigorated using Huangqi (Radix Astragali Mongolici), Gancao (Radix Glycyrrhizae), Baizhu (Rhizoma Atractylodis Macrocephalae) and Kuxingren (Semen Armeniacae Amarum). Moistening the intestine was possible with Kuxingren (Semen Armeniacae Amarum), Huomaren (Fructus Cannabis) and Jiegeng (Radix Platycodi). Also, moistening the lungs was done with Kuxingren (Semen Armeniacae Amarum), ventilating the lungs with Kuxingren (Semen Armeniacae Amarum) and Gualou (Fructus et Semen Trichosanthis), and nourishing the lungs with Huangqi (Radix Astragali Mongolici), Gancao (Radix Glycyrrhizae) and Kuxingren (Semen Armeniacae Amarum). These data demonstrated that Kuxingren (Semen ArmeniacaeAmarum) was a key agent. Our analyses of the literature showed clear relationships between

  2. Atrial fibrillation therapy now and in the future: drugs, biologicals, and ablation.

    Science.gov (United States)

    Woods, Christopher E; Olgin, Jeffrey

    2014-04-25

    Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is rapidly changing and improving. The purpose of this review is to summarize current state-of-the-art diagnostic and therapeutic modalities for treatment of AF. The review focuses on reviewing treatment as it relates to the pathophysiological basis of disease and reviews preclinical and clinical evidence for potential new diagnostic and therapeutic modalities, including imaging, biomarkers, pharmacological therapy, and ablative strategies for AF. Current ablation and drug therapy approaches to treating AF are largely based on treating the arrhythmia once the substrate occurs and is more effective in paroxysmal AF rather than persistent or permanent AF. However, there is much research aimed at prevention strategies, targeting AF substrate, so-called upstream therapy. Improved diagnostics, using imaging, genetics, and biomarkers, are needed to better identify subtypes of AF based on underlying substrate/mechanism to allow more directed therapeutic approaches. In addition, novel antiarrhythmics with more atrial specific effects may reduce limiting proarrhythmic side effects. Advances in ablation therapy are aimed at improving technology to reduce procedure time and in mechanism-targeted approaches.

  3. Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

    Science.gov (United States)

    Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

    2017-01-01

    Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

  4. Assessment of drug candidates for broad-spectrum antiviral therapy targeting cellular pyrimidine biosynthesis.

    Science.gov (United States)

    Marschall, Manfred; Niemann, Ina; Kosulin, Karin; Bootz, Anna; Wagner, Sabrina; Dobner, Thomas; Herz, Thomas; Kramer, Bernd; Leban, Johann; Vitt, Daniel; Stamminger, Thomas; Hutterer, Corina; Strobl, Stefan

    2013-12-01

    Currently available antiviral drugs frequently induce side-effects or selection of drug-resistant viruses. We describe a novel antiviral principle based on targeting the cellular enzyme dihydroorotate dehydrogenase (DHODH). In silico drug design and biochemical evaluation identified Compound 1 (Cmp1) as a selective inhibitor of human DHODH in vitro (IC50 1.5±0.2nM). Crystallization data specified the mode of drug-target interaction. Importantly, Cmp1 displayed a very potent antiviral activity that could be reversed by co-application of uridine or other pyrimidine precursors, underlining the postulated DHODH-directed mode of activity. Human and animal cytomegaloviruses as well as adenoviruses showed strong sensitivity towards Cmp1 in cell culture-based infection systems with IC50 values in the low micromolar to nanomolar range. Particularly, broad inhibitory activity was demonstrated for various types of laboratory and clinically relevant adenoviruses. For replication of human cytomegalovirus in primary fibroblasts, antiviral mode of activity was attributed to the early stage of gene expression. A mouse in vivo model proved reduced replication of murine cytomegalovirus in various organs upon Cmp1 treatment. These findings suggested Cmp1 as drug candidate and validated DHODH as a promising cellular target for antiviral therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Antibody-Drug Conjugates: A Clinical Pharmacy Perspective on an Emerging Cancer Therapy.

    Science.gov (United States)

    Jerjian, Taleen V; Glode, Ashley E; Thompson, Lisa A; O'Bryant, Cindy L

    2016-01-01

    Antibody-drug conjugates (ADCs) combine highly specific monoclonal antibodies with potent cytotoxic drugs. Their synergy allows for targeted delivery of toxic drugs to cancer cells while sparing systemic exposure. In this review, we focus on the history and clinical applications of ADCs approved by the U.S. Food and Drug Administration (FDA) for the treatment of cancer and highlight new ADCs in the drug development pipeline. Three ADCs have received FDA approval thus far. Gemtuzumab ozogamicin, although withdrawn from the U.S. market, may still be an effective treatment modality in subsets of patients with acute myeloid leukemia. Brentuximab vedotin and ado-trastuzumab emtansine have shown improved efficacy and safety data compared with standard chemotherapy for the treatment of advanced lymphoma and breast cancer, respectively. With a number of ADCs with promising preliminary data in the clinical trial pipeline, cancer therapy is moving forward from traditional chemotherapy to targeted treatment modalities driven by the specificity of monoclonal antibodies and advancing biotechnology. © 2016 Pharmacotherapy Publications, Inc.

  6. New drugs or alternative therapy to blurring the symptoms of fibromyalgia-a patent review.

    Science.gov (United States)

    Oliveira, Marlange A; Guimarães, Adriana G; Araújo, Adriano A S; Quintans-Júnior, Lucindo J; Quintans, Jullyana S S

    2017-10-01

    Fibromyalgia (FM) is a musculoskeletal condition characterized by chronic widespread pain, tenderness and often accompanied by other comorbid conditions such as depression, anxiety, chronic fatigue, among others. Now, we aimed to survey the recent patents describing new drugs or alternative therapy for FM. Areas covered: This review covers the therapeutic patents published between 2010 and 2017 from specialized search databases (WIPO, DERWENT, INPI, ESPANET and USPTO) that report the discovery of new drugs or pharmacologic alternative for the treatment of FM. Expert opinion: New therapeutic substances have been proposed in the last seven years. At least as it has been found in our survey, most are still in the pre-clinical phase of the study, and its clinical applicability is unclear. However, other therapeutic approaches were found in patents such as well-established drugs in the market in combination or drug repositioning that combines the 'new analgesic' effects with the old side effects. Hence, it is a safe approach for pharmaceutical market, but poorer to patients who need a radical innovation. So, there is the emerging need for further studies on the safety and efficacy of such therapeutic measures and the search for improvement of side effects, as well as the development of new drugs that are unorthodox for different FM symptoms.

  7. Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

    Directory of Open Access Journals (Sweden)

    Meigs James B

    2009-02-01

    Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

  8. Terpene compound drug as medical expulsive therapy for ureterolithiasis: a meta-analysis.

    Science.gov (United States)

    Chua, Michael Erlano; Park, Jane Hyeon; Castillo, Josefino Cortez; Morales, Marcelino Lopeztan

    2013-04-01

    The aim of this study is to investigate the efficacy of terpene compound drug (pinene, camphene, borneol, anethole, fenchone and cineol in olive oil) in facilitating spontaneous passage of ureteral calculi through meta-analysis of randomized controlled trials (RCT). Systematic literature search on MEDLINE, EMBASE, OVID, Science Direct, Proquest, Google scholar, Cochrane Library databases and reference list of related literatures were done without language restriction. RCTs on ureterolithiasis medical expulsive therapy (MET) that compare terpene compound drug versus placebo/control group or alpha-blockers were identified. Articles retrieved were critically appraised by two independent reviewers according to Cochrane Collaboration recommendations. Data from included studies were extracted for calculation of risk ratio (RR) and 95 % confidence interval (CI). Effect estimates were pooled using Mantel-Haenszel method with random effect model. Inter-study heterogeneity and publication bias were assessed. The PRISMA guidelines for meta-analysis reporting were followed. Five RCTs (total of 344 subjects) of adequate methodological quality were included. Pooled effect estimates from homogenous studies showed that compared to placebo/control group, patients treated with terpene compound drug had significantly better ureteral calculi spontaneous expulsion rate (pooled RR: 1.34; 95 % CI 1.12, 1.61). Subgroup analysis of studies that compare terpene compound drug with alpha-blockers showed no significant difference (pooled RR: 0.79; 95 % CI 0.59, 1.06), while significant inter-study heterogeneity was noted. Only minor gastrointestinal adverse effect was reported on terpene compound drug use. The results suggest that terpene compound drug as MET is effective in augmenting spontaneous passage of ureterolithiasis. High quality large-scale RCTs comparing alpha-blockers and terpene compound drug are warranted to make a more definitive conclusion.

  9. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    Science.gov (United States)

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that

  10. Stem cell therapy and tissue engineering for correction of congenital heart disease

    Science.gov (United States)

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects. PMID:26176009

  11. Stem cell therapy and tissue engineering for correction of congenital heart disease

    Directory of Open Access Journals (Sweden)

    Elisa eAvolio

    2015-06-01

    Full Text Available This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects.

  12. Stem cell therapy and tissue engineering for correction of congenital heart disease.

    Science.gov (United States)

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects.

  13. Hemophilia A inhibitor treatment: the promise of engineered T-cell therapy.

    Science.gov (United States)

    Parvathaneni, Kalpana; Abdeladhim, Maha; Pratt, Kathleen P; Scott, David W

    2017-09-01

    Hemophilia A is a bleeding disorder caused by mutations in the gene encoding factor VIII (FVIII), a cofactor protein that is essential for normal blood clotting. Approximately, 1 in 3 patients with severe hemophilia A produce neutralizing antibodies (inhibitors) that block its biologic function in the clotting cascade. Current efforts to eliminate inhibitors consist of repeated FVIII injections under what is termed an "ITI" protocol (Immune Tolerance Induction). However, this method is extremely costly and approximately 30% of patients undergoing ITI do not achieve peripheral tolerance. Human T regulatory cells (Tregs) have been proposed as a new strategy to treat this antidrug antibody response, as well as other diseases. Polyclonal Tregs are nonspecific and could potentially cause general immunosuppression. Novel approaches to induce tolerance to FVIII include the use of engineered human and mouse antigen-specific Tregs, or alternatively antigen-specific cytotoxic cells, to delete, anergize, or kill FVIII-specific lymphocytes. In this review, we discuss the current state of engineered T-cell therapies, and we describe the recent progress in applying these therapies to induce FVIII-specific tolerance. Published by Elsevier Inc.

  14. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Directory of Open Access Journals (Sweden)

    Martinović Žarko J.

    2004-01-01

    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  15. [Antiplatelet therapy: resistance to traditional antiaggregation drugs and role of new antiplatelet agents].

    Science.gov (United States)

    del Castillo-Carnevali, Hugo; Barrios Alonso, Vivencio; Zamorano Gómez, José Luis

    2014-09-09

    Platelet aggregation plays a key role in the development of major cardiovascular events (MACE) related to atherothrombosis. Since the appearance of coronary stenting, the importance of measuring and modulating platelet activity has considerably increased in the scientific literature during the last decade. Double antiplatelet therapy with aspirin and clopidogrel administrated to stent carriers has widely demonstrated its efficacy in the prevention of MACE compared with aspirin alone. These benefits are also present when a conservatory approach is chosen for acute coronary syndrome management. However, there are an important number of patients who develop MACE despite optimal dual antiplatelet therapy, most likely related to an incomplete platelet activity inhibition. Many studies suggest an important inter-individual variability in the response to the drugs, maybe related, at least in part, to the use of different assessment techniques of platelet aggregation. Other authors suggest an incomplete platelet inhibition as a possible explanation for the presence of MACE in patients under optimal antiplatelet therapy. Resistance to usual drugs has become a clinically relevant issue that requires an individual approach where new antiplatelet agents, such as prasugrel or ticagrelor, could play an important role as stated in current consensus documents. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  16. Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

    Directory of Open Access Journals (Sweden)

    Justin Cohen

    2017-08-01

    Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

  17. The Future of NMR Metabolomics in Cancer Therapy: Towards Personalizing Treatment and Developing Targeted Drugs?

    Science.gov (United States)

    Palmnas, Marie S.A.; Vogel, Hans J

    2013-01-01

    There has been a recent shift in how cancers are defined, where tumors are no longer simply classified by their tissue origin, but also by their molecular characteristics. Furthermore, personalized medicine has become a popular term and it could start to play an important role in future medical care. However, today, a “one size fits all” approach is still the most common form of cancer treatment. In this mini-review paper, we report on the role of nuclear magnetic resonance (NMR) metabolomics in drug development and in personalized medicine. NMR spectroscopy has successfully been used to evaluate current and potential therapies, both single-agents and combination therapies, to analyze toxicology, optimal dose, resistance, sensitivity, and biological mechanisms. It can also provide biological insight on tumor subtypes and their different responses to drugs, and indicate which patients are most likely to experience off-target effects and predict characteristics for treatment efficacy. Identifying pre-treatment metabolic profiles that correlate to these events could significantly improve how we view and treat tumors. We also briefly discuss several targeted cancer drugs that have been studied by metabolomics. We conclude that NMR technology provides a key platform in metabolomics that is well-positioned to play a crucial role in realizing the ultimate goal of better tailored cancer medicine. PMID:24957997

  18. The discontinuance of maintenance neuroleptic therapy in chronic schizophrenic patients: drug and social consequences.

    Science.gov (United States)

    Johnson, D A; Pasterski, G; Ludlow, J M; Street, K; Taylor, R D

    1983-05-01

    In a prospective follow-up the outcome of 60 chronic schizophrenic patients who discontinued neuroleptic therapy after remaining stable 12-48 months was compared with controls continuing medication. Not only did the drug-discontinued patients have more relapses (P less than 0.001), but the form of relapse was both more severe and acute, resulting in differences of self-injury (P less than 0.05), anti-social behaviour (P less than 0.01), inpatient admissions (P less than 0.001), and the use of compulsory powers (P less than 0.01). In patients who relapsed, both social and work function was affected adversely for some months. Patients who remained relapse-free without drugs (20%) had a level of work and social function similar to medicated patients. At the end of 18 months the patients who discontinued depot maintenance therapy were found to have been prescribed one-third more neuroleptic drugs than controls, with a possible increase in the risk of long-term tardive dyskinesia.

  19. Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Ponizovskiy MR

    2015-04-01

    Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

  20. Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis: A Systematic Review

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    Vera M. Kroesen

    2017-06-01

    Full Text Available Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs, in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.

  1. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ya-Shu [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Lu, Yu-Jen [Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Graduate Institute of Health Industry and Technology, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan, ROC (China)

    2017-04-01

    A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of

  2. Defined lipid analogues induce transient channels to facilitate drug-membrane traversal and circumvent cancer therapy resistance

    NARCIS (Netherlands)

    van Hell, Albert J.; Melo, Manuel N.; van Blitterswijk, Wim J.; Gueth, Dayana M.; Braumuller, Tanya M.; Pedrosa, Lilia R. C.; Song, Ji-Ying; Marrink, Siewert J.; Koning, Gerben A.; Jonkers, Jos; Verheij, Marcel

    2013-01-01

    Design and efficacy of bioactive drugs is restricted by their (in) ability to traverse cellular membranes. Therapy resistance, a major cause of ineffective cancer treatment, is frequently due to suboptimal intracellular accumulation of the drug. We report a molecular mechanism that promotes

  3. Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2018-01-01

    Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…

  4. Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?

    Directory of Open Access Journals (Sweden)

    Boris Michael Holzapfel

    2013-01-01

    Full Text Available Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

  5. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy.

    Science.gov (United States)

    Wang, Zhi-Yu; Chen, Meng; Zhu, Ling-Ling; Yu, Lu-Shan; Zeng, Su; Xiang, Mei-Xiang; Zhou, Quan

    2015-01-01

    . Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring.

  6. Recreational Drug and Psychosocial Profile in Chronic Hepatitis C Patients Seeking Antiviral Therapy.

    Science.gov (United States)

    George, Nayana; Harrell, Sherrie M; Rhodes, Kimberly D; Duarte-Rojo, Andres

    2018-01-01

    Practitioners treating hepatitis C (HCV) provide healthcare to a special population with high rates of substance abuse and psychiatric disorders. We investigated the psychosocial profile in HCV patients and tested what variables affect commencement of antiviral therapy. Recreational drug use (RDU), marijuana (THC), alcohol use, and psychiatric history were initially investigated with a questionnaire prior to history and physical. Following an educational intervention, we reinterrogated patients for RDU and THC use, and revision of initial statement was documented. Variables affecting commencement of antiviral therapy were analysed with logistic regression. Out of 153 patients, 140 (92%) answered the questionnaire. Intervention increased total yield by 6%, however, 39% (11/28) of those initially denying use revised their statement. Drug screening identified 9 more patients with RDU/THC use. Half of patients consuming alcohol were heavy drinkers, and psychiatric disease was identified in 54%. Only 73 (48%) of 139 patients eligible for antivirals received treatment. Multivariable analysis revealed that younger patients (OR = 1.04, 95% CI 1.01-1.08), and those testing positive on drug screen (OR = 0.41, 95% CI 0.19-0.92) were less likely to be treated. Denial by insurance and loss to follow-up were the most common reasons for not starting antiviral treatment. Substance abuse is highly prevalent among HCV patients, and it is difficult to tell prior from current users. Integral care of HCV patients should include a diligent screen for substance abuse and rehabilitation referral, aiming to increase the pool of patients eligible for antiviral therapy. This can only be achieved through a multidisciplinary approach.

  7. POLICE BRIBERY AND ACCESS TO METHADONE MAINTENANCE THERAPY WITHIN THE CONTEXT OF DRUG POLICY REFORM IN TIJUANA, MEXICO

    OpenAIRE

    Werb, D; Wagner, KD; Beletsky, L; Gonzalez-Zuniga, Patricia; Rangel, Gudelia; Strathdee, SA

    2015-01-01

    © 2015 Elsevier Ireland Ltd. In 2009, Mexico passed legislation to decriminalize drug possession and improve access to addiction treatment. We undertook research to assess the implementation of the reform among a cohort of people who inject drugs (PWID) in Tijuana. This study specifically sought to determine whether discretionary policing practices like extortion impact access to methadone maintenance therapy (MMT) in Tijuana, a city characterized by high levels of drug-related harms. Methods...

  8. Gene therapy strategies using engineered stem cells for treating gynecologic and breast cancer patients (Review).

    Science.gov (United States)

    Kim, Ye-Seul; Hwang, Kyung-A; Go, Ryeo-Eun; Kim, Cho-Won; Choi, Kyung-Chul

    2015-05-01

    There are three types of stem cells: embryonic stem (ES) cells, adult stem (AS) cells and induced pluripotent stem (iPS) cells. These stem cells have many benefits including the potential ability to differentiate into various organs. In addition, engineered stem cells (GESTECs) designed for delivering therapeutic genes may be capable of treating human diseases including malignant cancers. Stem cells have been found to possess the potential for serving as novel delivery vehicles for therapeutic or suicide genes to primary or metastatic cancer formation sites as a part of gene-directed enzyme/prodrug combination therapy (GEPT). Given the advantageous properties of stem cells, tissue-derived stem cells are emerging as a new tool for anticancer therapy combined with prodrugs. In this review, the effects of GESTECs with different origins, i.e., neural, amniotic membrane and amniotic fluid, introduced to treat patients with diverse types of gynecologic and breast cancers are discussed. Data from the literature indicate the therapeutic potential of these cells as a part of gene therapy strategies to selectively target malignancies in women at clinically terminal stages.

  9. Endoscopic laryngeal patterns in vagus nerve stimulation therapy for drug-resistant epilepsy.

    Science.gov (United States)

    Felisati, Giovanni; Gardella, Elena; Schiavo, Paolo; Saibene, Alberto Maria; Pipolo, Carlotta; Bertazzoli, Manuela; Chiesa, Valentina; Maccari, Alberto; Franzini, Angelo; Canevini, Maria Paola

    2014-01-01

    In 30% of patients with epilepsy seizure control cannot be achieved with medications. When medical therapy is not effective, and epilepsy surgery cannot be performed, vagus nerve stimulator (VNS) implantation is a therapeutic option. Laryngeal patterns in vagus nerve stimulation have not been extensively studied yet. The objective was to evaluate laryngeal patterns in a cohort of patients affected by drug-resistant epilepsy after implantation and activation of a vagus nerve stimulation therapy device. 14 consecutive patients underwent a systematic otolaryngologic examination between 6 months and 5 years after implantation and activation of a vagus nerve stimulation therapy device. All patients underwent fiberoptic endoscopic evaluation, which was recorded on a portable device allowing a convenient slow-motion analysis of laryngeal patterns. All recordings were blindly evaluated by two of the authors. We observed three different laryngeal patterns. Four patients showed left vocal cord palsy at the baseline and during vagus nerve stimulation; seven showed left vocal cord palsy at the baseline and left vocal cord adduction during vagus nerve stimulation; and three patients showed a symmetric pattern at the baseline and constant left vocal cord adduction during vagus nerve stimulation. These laryngeal findings are here described for the first time in the literature and can be only partially explained by existing knowledge of laryngeal muscles and vagus nerve physiology. This might represent a new starting point for studies concerning laryngeal physiology and phonation, while the vagus nerve stimulation therapy could act as a new and ethical experimental model for human laryngeal physiology.

  10. DOMESTIC SPECTRUM OF ANTIVIRAL DRUG — UMIFENOVIR AS ETIOTROPIC THERAPY OF INFLUENZA

    Directory of Open Access Journals (Sweden)

    L. V. Osidak

    2016-01-01

    Full Text Available In this article are presented the results of comparative observation of the effectiveness of the inclusion in the complex therapy of 203 hospitalized children aged 2 years and older with influenza А(Н1N1pdm09 domestic antiviral drug — Umifenovir  (Arbidol that occurred during the epidemic seasons 2009—2013 and 2015—2016 in terms of observational clinical studies.  It is shown  that this drug, possessing a wide spectrum of antiviral activity, including against Oseltamivir — and Zanamivir-resistant influenza virus strains, antioxidant activity and low toxicity (Code ATX Ј05АХ13, can be successfully used in the treatment of infants with influenza А(Н1N1pdm09.

  11. Metal-Organic Framework (MOF)-Based Drug/Cargo Delivery and Cancer Therapy.

    Science.gov (United States)

    Wu, Ming-Xue; Yang, Ying-Wei

    2017-06-01

    Metal-organic frameworks (MOFs)-an emerging class of hybrid porous materials built from metal ions or clusters bridged by organic linkers-have attracted increasing attention in recent years. The superior properties of MOFs, such as well-defined pore aperture, tailorable composition and structure, tunable size, versatile functionality, high agent loading, and improved biocompatibility, make them promising candidates as drug delivery hosts. Furthermore, scientists have made remarkable achievements in the field of nanomedical applications of MOFs, owing to their facile synthesis on the nanoscale and alternative functionalization via inclusion and surface chemistry. A brief introduction to the applications of MOFs in controlled drug/cargo delivery and cancer therapy that have been reported in recent years is provided here. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. CURRENT POSSIBILITIES OF DRUG THERAPY FOR CASTRATION-RESISTANT PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Markova

    2014-07-01

    Full Text Available The advent of a variety of new drugs to treat castration-resistant prostate cancer (CRPC, which have demonstrated their efficacy in increasing overall and progression-free survival, has considerably enhanced treatment possibilities in this category of patients. The standard treatment of metastatic CRPC (mCRPC remains to be first-line chemotherapy with docetaxel 75 mg/m2 in combination with prednisolone 10 mg/day every 3 weeks. The new drugs also available in Russia are cabazitaxel and abiraterone acetate, which are approved for second-line treatment in mCRPC patients treated with docetaxel. The optimum sequence of therapy and the time of its use in view of the heterogeneity of a CRPC patient population remain open.

  13. CURRENT POSSIBILITIES OF DRUG THERAPY FOR CASTRATION-RESISTANT PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Markova

    2013-01-01

    Full Text Available The advent of a variety of new drugs to treat castration-resistant prostate cancer (CRPC, which have demonstrated their efficacy in increasing overall and progression-free survival, has considerably enhanced treatment possibilities in this category of patients. The standard treatment of metastatic CRPC (mCRPC remains to be first-line chemotherapy with docetaxel 75 mg/m2 in combination with prednisolone 10 mg/day every 3 weeks. The new drugs also available in Russia are cabazitaxel and abiraterone acetate, which are approved for second-line treatment in mCRPC patients treated with docetaxel. The optimum sequence of therapy and the time of its use in view of the heterogeneity of a CRPC patient population remain open.

  14. Drug-resistant tuberculosis among HIV-infected patients starting antiretroviral therapy in Durban, South Africa.

    Directory of Open Access Journals (Sweden)

    Jeffrey K Hom

    Full Text Available To estimate the prevalence of drug-resistant tuberculosis (TB and describe the resistance patterns in patients commencing antiretroviral therapy (ART in an HIV clinic in Durban, South Africa.Cross-sectional cohort study.Consecutive HIV-infected adults (≥ 18y/o initiating HIV care were enrolled from May 2007-May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium. Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42-150/µl. 267 subjects (26% reported a prior history of TB and 210 (20% were receiving TB treatment at enrollment; 191 (18% subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0-12.4. Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9-30.5 compared to 5.2% (95% CI 2.1-8.9 among those with no prior TB. 5.1% (95% CI 2.4-9.5 had rifampin or rifampin plus INH resistance.The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.

  15. Synthesis and Applications of Multimodal Hybrid Albumin Nanoparticles for Chemotherapeutic Drug Delivery and Photothermal Therapy Platforms

    Science.gov (United States)

    Peralta, Donna V.

    Progress has been made in using human serum albumin nanoparticles (HSAPs) as carrier systems for targeted treatment of cancer. Human serum albumin (HSA), the most abundant human blood protein, can form HSAPs via a desolvation and crosslinking method, with the size of the HSAPs having crucial importance for drug loading and in vivo performance. Gold nanoparticles have also gained medicinal attention due to their ability to absorb near-infrared (NIR) light. These relatively non-toxic particles offer combinational therapy via imaging and photothermal therapy (PPTT) capabilities. A desolvation and crosslinking approach was employed to encapsulate gold nanoparticles (AuNPs), hollow gold nanoshells (AuNSs), and gold nanorods (AuNRs), into efficiently sized HSAPs for future tumor heat ablation via PPTT. The AuNR-HSAPs, AuNP-HSAPs and AuNS-HSAPs had average particle diameters of 222 +/- 5, 195 +/- 9 and 156 +/- 15, respectively. We simultaneously encapsulated AuNRs and the anticancer drug paclitaxel (PAC), forming PAC-AuNR-HSAPs with overall average particle size of 299 +/- 6 nm. Loading of paclitaxel into PAC-AuNR-HSAPs reached 3microg PAC/mg HSA. PAC-AuNR-HSAPs experienced photothermal heating of 46 °C after 15 minutes of NIR laser exposure; the temperature necessary to cause severe cellular hyperthermia. There was a burst release of paclitaxel up to 188 ng caused by the irradiation session, followed by a temporal drug release. AuNR-HSAPs were tested for ablation of renal cell carcinoma using NIR irradiation in vitro. Particles created with the same amount of AuNRs, but varying HSA (1, 5 or 20 mg) showed overall particle size diameters 409 +/- 224, 294 +/- 83 and 167 +/- 4 nm, respectively. Increasing HSAPs causes more toxicity under non-irradiated treatment conditions: AuNR-HSAPs with 20 mg versus 5 mg HSA caused cell viability of 64.5% versus 87%, respectively. All AuNR-HSAPs batches experienced photothermal heating above 42 °C. Coumarin-6, was used to visualize the

  16. 131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment.

    Science.gov (United States)

    Ding, Yong; Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

    2016-02-01

    The aim of this study is to evaluate the safety and long-term results of (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with (131)I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to (131)I therapy, all patients were given low-iodine diet. The dose of (131)I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total (131)I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. © 2015 by the Society for Experimental Biology and Medicine.

  17. 131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment

    Science.gov (United States)

    Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

    2015-01-01

    The aim of this study is to evaluate the safety and long-term results of 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with 131I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to 131I therapy, all patients were given low-iodine diet. The dose of 131I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total 131I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. PMID:26341470

  18. Family mechanisms of structural ecosystems therapy for HIV-seropositive women in drug recovery.

    Science.gov (United States)

    Mitrani, Victoria B; McCabe, Brian E; Burns, Myron J; Feaster, Daniel J

    2012-09-01

    Examined the effects of Structural Ecosystems Therapy (SET), a family intervention for women living with HIV or AIDS, compared to a psycho-educational health group (HG) intervention, and reciprocal relationships between women and family members. Women (n = 126) and their family members (n = 269) were randomized to one of two conditions and assessed every 4 months for 12 months. Family functioning, drug use, and psychological distress was reported by multiple family members. Multilevel growth curve modeling showed a different family functioning trajectory between SET and HG, B = -0.05, SE = 0.02, p family-level drug abstinence or psychological distress, but there was a significant difference in the trajectory of psychological distress after controlling for change in family functioning, B = -0.28, SE = 0.13, p family functioning to change in psychological distress, B = 0.29, SE = 0.12, p family drug abstinence significantly predicted women's abstinence 4 months later, B = 0.22, SE = 0.06, p family members and the impact of family in relapse prevention and partially supported SET's potential for maintaining family functioning and well-being for women living with HIV or AIDS in drug recovery. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  19. Activation of Macrophages: Establishing a Role for Polysaccharides in Drug Delivery Strategies Envisaging Antibacterial Therapy.

    Science.gov (United States)

    Rodrigues, Susana; Grenha, Ana

    2015-01-01

    Infectious diseases are an important health concern, as several pathogens have developed the ability to survive inside phagocytic cells (mostly macrophages), encountered at early infection stages, using these cells as trojan horses. In fact, in several cases macrophages have become a nutrient reservoir that helps pathogens to grow in number and spread. It is frequent that conventional therapeutic schedules include long periods of drug intake, at high doses, in some cases leading to severe side effects and clinical relapses due to prolonged intake, along with an increased risk for the development of antibiotic resistances. Therefore, there is a compelling need to develop new therapeutic strategies providing a targeted drug delivery to macrophages. These cells have unique surface receptors that might recognise preferentially several polysaccharide moieties present on the surface of infecting organisms, including in the bacterial cell wall. Benefiting from a similar composition regarding the referred moieties, polysaccharides might be good candidates to compose the matrix of drug carriers aimed at macrophage targeting, as they can use the same recognition pathways of the infecting organisms. This review describes the features and the role of macrophages in infectious conditions, while addressing their potential as therapeutic targets and unravelling the prominent role of polysaccharides as matrix materials of drug delivery systems developed for the therapy of infectious diseases.

  20. Drug Therapy in the Progressed CML Patient with multi-TKI Failure.

    Science.gov (United States)

    Haznedaroglu, Ibrahim C

    2015-01-01

    The aim of this paper is to outline pharmacotherapy of the 'third-line management of CML' (progressive disease course after sequential TKI drugs). Current management of CML with multi-TKI failure is reviewed. TKI (bosutinib, ponatinib, dasatinib, nilotinib) and non-TKI (omacetaxine mepussecinate, IFN or PEG-IFN) drugs are available. The literature search was made in PubMed with particular focus on the clinical trials, recommendations, guidelines and expert opinions, as well as international recommendations. Progressing CML disease with multi-TKI failure should be treated with alloSCT based on the availability of the donor and EBMT transplant risk scores. The TKI and non-TKI drugs shall be used to get best promising (hematological, cytogenetic, molecular) response. During the CP-CML phase of multi-TKI failure, 2nd generation TKIs (nilotinib or dasatinib) should be tried if not previously utilized. Bosutinib and ponatinib (3rd-generation TKIs) should be administered in double- or triple-TKI (imatinib and nilotinib and dasatinib) resistant patients. The presence of T315I mutation at any phase requires ponatinib or omacetaxine mepussecinate therapy before allografting. During the AP/BC-CML phase of multi-TKI failure, the most powerful TKI available (ponatinib or dasatinib if not previously used) together with chemotherapy should be given before alloSCT. Monitoring of CML disease and drug off-target risks (particularly vascular thrombotic events) are vital.

  1. An alternative therapy for drug-resistant epilepsy: transcutaneous auricular vagus nerve stimulation.

    Science.gov (United States)

    Rong, Peijing; Liu, Aihua; Zhang, Jianguo; Wang, Yuping; Yang, Anchao; Li, Liang; Ben, Hui; Li, Liping; Liu, Rupeng; He, Wei; Liu, Huanguang; Huang, Feng; Li, Xia; Wu, Peng; Zhu, Bing

    2014-01-01

    Previous studies demonstrated that vagus nerve stimulation (VNS) is an effective therapy for drug-resistant epilepsy. Acupuncture is also used to treat epilepsy. This study was designed to examine the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with drug-resistant epilepsy. A total of 50 volunteer patients with drug-resistant epilepsy were selected for a random clinical trial to observe the therapeutic effect of ta-VNS. The seizure frequency, quality of life, and severity were assessed in weeks 8, 16, and 24 of the treatment according to the percentage of seizure frequency reduction. In the pilot study, 47 of the 50 epilepsy patients completed the 24-week treatment; three dropped off. After 8-week treatment, six of the 47 patients (12%) were seizure free and 12 (24%) had a reduction in seizure frequency. In week 16 of the continuous treatment, six of the 47 patients (12%) were seizure free; 17 (34%) had a reduction in seizure frequency. After 24 weeks' treatment, eight patients (16%) were seizure free; 19 (38%) had reduced seizure frequency. Similar to the therapeutic effect of VNS, ta-VNS can suppress epileptic seizures and is a safe, effective, economical, and widely applicable treatment option for drug-resistant epilepsy. (ChiCTR-TRC-10001023).

  2. DRUG THERAPY IN THE PROGRESSED CML PATIENT WITH MULTI-TKI FAILURE

    Directory of Open Access Journals (Sweden)

    Ibrahim C. Haznedaroglu

    2015-02-01

    Full Text Available The aim of this paper is to outline pharmacotherapy of the ‘third-line management of CML’ (progressive disease course after sequential TKI drugs. Current management of CML with multi-TKI failure is reviewed. TKI (bosutinib, ponatinib, dasatinib, nilotinib and non-TKI (omacetaxine mepussecinate, IFN or PEG-IFN drugs are available. The literature search was made in PubMed with particular focus on the clinical trials, recommendations, guidelines and expert opinions, as well as international recommendations. Progressing CML disease with multi-TKI failure should be treated with alloSCT based on the availability of the donor and EBMT transplant risk scores. The TKI and non-TKI drugs shall be used to get best promising (hematological, cytogenetic, molecular response. During the CP-CML phase of multi-TKI failure, 2nd generation TKIs (nilotinib or dasatinib are used if they remained. Bosutinib and ponatinib (3rd generation TKIs can be administered in triple-TKI failed (imatinib and nilotinib and dasatinib patients. The presence of T315I mutation at any phase requires ponatinib or omacetaxine mepussecinate therapy before allografting. During the AP/BC-CML phase of multi-TKI failure, the most powerful TKI available (ponatinib or dasatinib if remained together with chemotherapy should be given before alloSCT. Monitoring of CML disease and drug off-target risks (particularly vascular thrombotic events are vital.

  3. One-Step Nanoengineering of Hydrophobic Photosensitive Drugs for the Photodynamic Therapy.

    Science.gov (United States)

    Zhou, Chao; Abbas, Manzar; Zhang, Min; Zou, Qianli; Shen, Guizhi; Chen, Chengjun; Peng, Hongshang; Yan, Xuehai

    2015-12-01

    Nanoengineering of anticancer therapeutic drugs including photosensitizers is highly desired and extremely required for improved therapeutic efficacy. It remains a formidable challenge to achieve nanostructured colloidal particles directly starting from hydrophobic drugs due to their hydrophobic nature and ready aggregation in aqueous ambient. In this work, we report a facile method for a one-pot preparation of hydrophobic photosensitizer nanoparticles by coating with different types of polyelectrolyte as stabilizing agents. Regardless of negatively or positively charged polyelectrolyte used, including Poly-L-lysine (PLL, MW = 15 k-30 k), PLL (MW = 30 k-70 k), heparin, and hyaluronic acid (HA), the hydrophobic photosensitizer BDEA (2,5-Bis(4-(diethylamino)benzylidene)cyclopentanone) as a model drug can be readily manipulated into stable and well-dispersed nanoparticles with size of average 120 nm. Stabilization presumably contributes to electrostatic repulsion of the adsorbed polyelectrolyte layer onto nanoparticles. Their anticancer activity against the HeLa cell line shows that the endocytic internalization of these nanosystems is associated with antiproliferative effects after irradiation with visible light. The one-step preparation strategy may be an alternative approach for the design of nano-formulations of hydrophobic photosensitive drugs, presenting a potential for photodynamic antitumor therapy.

  4. Microtubule inhibitor-based antibody–drug conjugates for cancer therapy

    Directory of Open Access Journals (Sweden)

    Klute K

    2014-12-01

    Full Text Available Kelsey Klute,1,* Eleni Nackos,1,* Shinsuke Tasaki,1 Daniel P Nguyen,2 Neil H Bander,2 Scott T Tagawa1,2 1Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA; 2Department of Urology, Weill Cornell Medical College, New York, NY, USA *These authors contributed equally to this work Abstract: The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their use as single agents in oncology has proven limited to date. The development of antibody-drug conjugates (ADCs takes advantage of the specificity of the monoclonal antibody and potent cytotoxic effect of chemotherapy, leading to enhanced cytotoxicity in target cells and limiting toxicity to normal tissue. Microtubules represent a validated oncologic target in a range of tumor types, with a number of anti-microtubule targeting cytotoxic drugs approved for cancer use. The systemic use of potent microtubule-binding agents is limited by their effects in normal cells, which leads to toxicity including myelosuppression and peripheral neuropathy. Linking these agents to monoclonal antibodies may limit toxicity to normal tissues and increase drug concentration in target tissues, also allowing the use of more potent agents which would be too toxic to administer in their unbound form. Two such ADCs have been approved for clinical use and many others are in development. Here we review the characteristics of each of the ADC components that have led to efficacious therapies and discuss some of the tubulin inhibitor-based ADCs in development for cancer therapy. Keywords: monoclonal antibody, antibody–drug conjugate, microtubule inhibitor

  5. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  6. Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies

    Directory of Open Access Journals (Sweden)

    Chau Yee Ng

    2018-01-01

    Full Text Available Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs, such as Stevens-Johnson syndrome (SJS and toxic epidermal necrosis (TEN with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite. Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

  7. Tuberculosis therapeutics: Engineering of nanomedicinal systems for local delivery of targeted drug cocktails

    Science.gov (United States)

    D'Addio, Suzanne M.

    In this thesis, a multifunctional nanocarrier drug delivery system was investigated and optimized to improve tuberculosis therapy by promoting the intracellular delivery of high payloads of antibiotics. To meet the needs of a patient population which continues to grow by close to 10 million people a year, innovative therapeutics must be formulated by robust and scalable processes. We use Flash NanoPrecipitation for the continuous precipitation of nanocarriers by block copolymer directed assembly, which enables the development of nanocarriers with tunable properties. Stable nanocarriers of Rifampicin and a hydrophobic Rifampicin prodrug have efficacy against tuberculosis in vitro that is equivalent to the soluble Rifampicin. To overcome poor in vivo efficacy of the recently discovered antitubercular drug SQ641, we co-encapsulate SQ641 and Cyclosporine A in a stable aqueous nanocarrier suspension, which enables drug administration and also enhances intracellular accumulation and antitubercular efficacy relative to SQ641 in solution. Since the mannose receptor is involved in the phagocytosis of tuberculosis bacilli, we modify the surface of nanocarriers with mannoside residues to target specific intracellular accumulation in macrophages. The surface density of mannoside terminated polyethylene glycol chains was controlled between 0 and 75% and in vitro cellular association reveals a 9% surface density is optimal for internalization mediated by the mannose receptor. We explore the preparation of large, porous aerosol carrier particles of with tunable deposition characteristics by spray freeze drying with ultrasonic atomization for direct dosing to the lungs. Nanocarriers are loaded at 3 - 50 wt% in mannitol particles with constant size, limited nanocarrier aggregation, and 63% dose delivered to the lungs, as determined by in vitro cascade impaction. There has been a lag in the development of new technologies to facilitate development and commercialization of

  8. Systems Analysis of Drug-Induced Receptor Tyrosine Kinase Reprogramming Following Targeted Mono- and Combination Anti-Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Alexey Goltsov

    2014-06-01

    Full Text Available The receptor tyrosine kinases (RTKs are key drivers of cancer progression and targets for drug therapy. A major challenge in anti-RTK treatment is the dependence of drug effectiveness on co-expression of multiple RTKs which defines resistance to single drug therapy. Reprogramming of the RTK network leading to alteration in RTK co-expression in response to drug intervention is a dynamic mechanism of acquired resistance to single drug therapy in many cancers. One route to overcome this resistance is combination therapy. We describe the results of a joint in silico, in vitro, and in vivo investigations on the efficacy of trastuzumab, pertuzumab and their combination to target the HER2 receptors. Computational modelling revealed that these two drugs alone and in combination differentially suppressed RTK network activation depending on RTK co-expression. Analyses of mRNA expression in SKOV3 ovarian tumour xenograft showed up-regulation of HER3 following treatment. Considering this in a computational model revealed that HER3 up-regulation reprograms RTK kinetics from HER2 homodimerisation to HER3/HER2 heterodimerisation. The results showed synergy of the trastuzumab and pertuzumab combination treatment of the HER2 overexpressing tumour can be due to an independence of the combination effect on HER3/HER2 composition when it changes due to drug-induced RTK reprogramming.

  9. Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug-Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2016-01-20

    Digoxin, a narrow therapeutic index drug, is widely used in congestive heart failure. However, the digitalization therapy involves dose titration and can exhibit drug-drug interaction. Ctrough versus area under the plasma concentration versus time curve in a dosing interval of 24 hours (AUC0-24h) and Cmax versus AUC0-24h for digoxin were established by linear regression. The predictions of digoxin AUC0-24h values were performed using published Ctrough or Cmax with appropriate regression lines. The fold difference, defined as the quotient of the observed/predicted AUC0-24h values, was evaluated. The mean square error and root mean square error, correlation coefficient (r), and goodness of the fold prediction were used to evaluate the models. Both Ctrough versus AUC0-24h (r = 0.9215) and Cmax versus AUC0-24h models for digoxin (r = 0.7781) showed strong correlations. Approximately 93.8% of the predicted digoxin AUC0-24h values were within 0.76-fold to 1.25-fold difference for Ctrough model. In sharp contrast, the Cmax model showed larger variability with only 51.6% of AUC0-24h predictions within 0.76-1.25-fold difference. The r value for observed versus predicted AUC0-24h for Ctrough (r = 0.9551; n = 177; P < 0.001) was superior to the Cmax (r = 0.6134; n = 275; P < 0.001) model. The mean square error and root mean square error (%) for the Ctrough model were 11.95% and 16.2% as compared to 67.17% and 42.3% obtained for the Cmax model. Simple linear regression models for Ctrough/Cmax versus AUC0-24h were derived for digoxin. On the basis of statistical evaluation, Ctrough was superior to Cmax model for the prediction of digoxin AUC0-24h and can be potentially used in a prospective setting for predicting drug-drug interaction or lack of it.

  10. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy

    Directory of Open Access Journals (Sweden)

    Wang ZY

    2015-03-01

    inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole, the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers. The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4, paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1.Conclusion: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring. Keywords: clopidogrel, drug–drug interactions, drug metabolism, drug transporter, genotype, pharmacokinetics, polypharmacy, pharmacogenetics, P2Y12 receptor inhibitors, risk management 

  11. Potential of using boric acid as a boron drug for boron neutron capture therapy for osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, C.F.; Lin, S.Y. [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Peir, J.J. [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Liao, J.W. [Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan (China); Lin, Y.C. [Department of Veterinary Medicine, National Chung Hsing University, Taiwan (China); Chou, F.I., E-mail: fichou@mx.nthu.edu.tw [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China)] [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China)

    2011-12-15

    Osteosarcoma is a malignant tumor commonly found in human and animals. The ability of boric acid (BA) to accumulate in osteosarcoma due to the mechanism of the bone formation of cancer cells would make boron neutron capture therapy (BNCT) an alternative therapy for osteosarcoma. This study evaluated the feasibility of using BA as the boron drug for BNCT of bone cancer. The cytotoxicity of BA to L929 cells exceeded that of UMR-106 cells. With 25 {mu}g {sup 10}B/mL medium of BA treatment, the boron concentration in UMR-106 cells was higher than that in L929 cells. The biodistribution and pharmacokinetics of BA in Sprague-Dawley (SD) rats were studied by administrating 25 mg {sup 10}B/kg body weight to SD rats. Blood boron level decreased rapidly within one hour after BA injection. Boron concentration in the long bone was 4-6 time higher than that of blood. Results of this study suggest that BA may be a potential drug for BNCT for osteosarcoma.

  12. Comparison of two different drug therapies for acute retinal necrosis syndrome

    Directory of Open Access Journals (Sweden)

    Jing Yuan

    2016-07-01

    Full Text Available AIM: To investigate clinical efficacy of two drug therapies(acyclovir with prednisone acetate tablets, ganciclovir with prednisone acetate tablets and aspirinfor acute retinal necrosis syndrome. METHODS: Thirty patients(40 eyeswith acute retinal necrosis syndrome in our hospital were randomly divided into group A and B. Group A was treated with acyclovir with prednisone acetate tablets, and group B was given ganciclovir with prednisone acetate tablets and aspirin. Clinical effects in the two groups were observed and compared. RESULTS: After treatment, the overall response rate in group B(90%was obviously higher than that in group A(70%, both of two regimens were effective, without significant difference(P>0.05. There was no significant difference on the pre-treatment visual acuity between the two groups(P>0.05. After different treatments, the visual acuity in group B was ≥0.5 in 12 eyes, 0.1≤andPPCONCLUSION: Two drug therapies(acyclovir with prednisone acetate tablets, ganciclovir with prednisone acetate tablets and aspirinboth have positive therapeutic effect, but the latter can better restore visual acuity and decrease the complications.

  13. Antiepileptic Drug Removal by Continuous Renal Replacement Therapy: A Review of the Literature.

    Science.gov (United States)

    Mahmoud, Sherif Hanafy

    2017-01-01

    Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted. A total of 31 case reports discussing 32 patients were found. AEDs reported were levetiracetam (n = 3), valproic acid (n = 9), carbamazepine (n = 10), phenytoin (n = 3), phenobarbital (n = 4), lacosamide (n = 1), gabapentin (n = 1), and topiramate (n = 1). Two-thirds of the reports were about using CRRT in drug overdose and one-third was about AED removal by CRRT during therapy. Based on the current limited evidence and pharmacokinetic characteristics of AEDs, renally eliminated AEDs and/or AEDs with limited protein binding such as levetiracetam are more likely to be removed by CRRT than AEDs that are mainly metabolized and extensively protein bound such as carbamazepine. In conclusion, there is not enough evidence to provide robust dosing recommendations for AEDs in patients undergoing CRRT. Further studies are needed.

  14. [Evaluation of a programme to monitor drug therapy in type-2 diabetics].

    Science.gov (United States)

    Fornos Pérez, J A; Guerra García, M M; Andrés Rodríguez, N F; Egea Ibernón, B

    2004-06-15

    To evaluate the results of pharmaceutical intervention in a programme to monitor the drug therapy of type-2 diabetics; and to assess the improvement of the indicators, glycosylated haemoglobin, basal glycaemia, lipid profile, albumin/creatinine, blood pressure, BMI, medication-related problems and adherence. Randomised clinical trial. 14 local pharmacies in the province of Pontevedra (Galicia), Spain. 126 type-2 diabetics, over 18 years old and who joined voluntarily a monitoring programme, distributed 50-50 into intervention and control groups. The main variable was HbA1c. Other variables were: clinical indicators of metabolic control (mean basal glycaemia, lipid profile), blood pressure, BMI, medication-related problems, understanding of the illness and its complications, adherence to medical treatment and to changes in life-style, and incidence of complications. Introduction and randomisation of patients. Recording of the initial status of the research variables, study and assessment stage, pharmaceutical interventions to detect and resolve any passing medication-related problems and educational activities. Referral to family doctor if his/her intervention required. Follow-up lasted 12 months with monthly scheduled visits and on-demand visits, after which the variables were assessed once more. The stages of study, evaluation, intervention and education did not occur in the control group. The study will enable the role of the chemist in achieving the objectives of controlling type-2 diabetes patients to be achieved through educational intervention and assistance in drug therapy monitoring.

  15. [Drug Therapy for Shock-Resistant Ventricular Fibrillation: Comparison of Nifekalant and Amiodarone].

    Science.gov (United States)

    Harayama, Nobuya; Nihei, Shun-Ichi; Nagata, Keiji; Aibara, Keiji; Kamochi, Masayuki; Sata, Takeyoshi

    2016-03-01

    Early direct current (DC) shock is the most important therapy for ventricular fibrillation. Following the increased availability of automated external defibrillators (AED), the survival rate of cardiopulmonary arrest patients with ventricular fibrillation has improved. Although patients with shock-resistant ventricular fibrillation require additional antiarrhythmic drug therapy, the optimal protocol has not been established. Nifekalant is a pure potassium channel blocker with a pyrimidinedione structure. Nifekalant was approved in Japan for the treatment of life-threatening ventricular tachyarrhythmias in 1999, and is widely used as a class III antiarrhythmic intravenous drug. Intravenous amiodarone was approved in Japan in 2007, and exhibits various effects on ion channels, receptors, sympathetic activity, and thyroid function. Nifekalant and amiodarone also exhibit many pharmacological and pharmacodynamic differences. As nifekalant has no negative inotropic effect and a rapid action and clearance with a short half-life, it has some advantages over amiodarone for use in cardiopulmonary resuscitation. Indeed, data from clinical and animal studies suggest that nifekalant is superior to amiodarone for resuscitation of cardiopulmonary arrest resulting from shock-resistant ventricular fibrillation. A 300-mg bolus intravenous injection of amiodarone is considered an overdose for resuscitation of shock-resistant ventricular fibrillation. Further clinical studies are required to evaluate the effects of nifekalant compared with amiodarone, and to determine the optimal dose of amiodaone, for resuscitation of shock-resistant ventricular fibrillation.

  16. Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kuang-Kai; Wang, Chi-Ching; Chao, Jui-I [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30013, Taiwan (China); Zheng, Wen-Wei; Lo, Yu-Shiu; Chen, Chinpiao [Department of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan (China); Chiu, Yu-Chung; Cheng, Chia-Liang, E-mail: clcheng@mail.ndhu.edu.tw, E-mail: chinpiao@mail.ndhu.edu.tw, E-mail: jichao@faculty.nctu.edu.tw [Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan (China)

    2010-08-06

    A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 {mu}g ml{sup -1} ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.

  17. Utility of Glioblastoma Patient-Derived Orthotopic Xenografts in Drug Discovery and Personalized Therapy.

    Science.gov (United States)

    Patrizii, Michele; Bartucci, Monica; Pine, Sharon R; Sabaawy, Hatem E

    2018-01-01

    Despite substantial effort and resources dedicated to drug discovery and development, new anticancer agents often fail in clinical trials. Among many reasons, the lack of reliable predictive preclinical cancer models is a fundamental one. For decades, immortalized cancer cell cultures have been used to lay the groundwork for cancer biology and the quest for therapeutic responses. However, cell lines do not usually recapitulate cancer heterogeneity or reveal therapeutic resistance cues. With the rapidly evolving exploration of cancer "omics," the scientific community is increasingly investigating whether the employment of short-term patient-derived tumor cell cultures (two- and three-dimensional) and/or patient-derived xenograft models might provide a more representative delineation of the cancer core and its therapeutic response. Patient-derived cancer models allow the integration of genomic with drug sensitivity data on a personalized basis and currently represent the ultimate approach for preclinical drug development and biomarker discovery. The proper use of these patient-derived cancer models might soon influence clinical outcomes and allow the implementation of tailored personalized therapy. When assessing drug efficacy for the treatment of glioblastoma multiforme (GBM), currently, the most reliable models are generated through direct injection of patient-derived cells or more frequently the isolation of glioblastoma cells endowed with stem-like features and orthotopically injecting these cells into the cerebrum of immunodeficient mice. Herein, we present the key strengths, weaknesses, and potential applications of cell- and animal-based models of GBM, highlighting our experience with the glioblastoma stem-like patient cell-derived xenograft model and its utility in drug discovery.

  18. Novel drug combination for Mycobacterium abscessus disease therapy identified in a Drosophila infection model.

    Science.gov (United States)

    Oh, Chun-Taek; Moon, Cheol; Park, Ok Kyu; Kwon, Seung-Hae; Jang, Jichan

    2014-06-01

    Mycobacterium abscessus is known to be the most drug-resistant Mycobacterium and accounts for ∼80% of pulmonary infections caused by rapidly growing mycobacteria. This study reports a new Drosophila melanogaster-M. abscessus infection model that can be used as an in vivo efficacy model for anti-M. abscessus drug potency assessment. D. melanogaster were challenged with M. abscessus, and infected flies were fed with a fly medium containing tigecycline, clarithromycin, linezolid, clofazimine, moxifloxacin, amikacin, cefoxitin, dinitrobenzamide or metronidazole at different concentrations (0, 100 and 500 mg/L). The survival rates of infected flies were plotted and bacterial colonization/dissemination in fly bodies was monitored by cfu determination and green fluorescent protein epifluorescence. The D. melanogaster-M. abscessus model enabled an assessment of the effectiveness of antibiotic treatment. Tigecycline was the best drug for extending the lifespan of M. abscessus-infected Drosophila, followed by clarithromycin and linezolid. Several different combinations of tigecycline, linezolid and clarithromycin were tested to determine the best combination. Tigecycline (25 mg/L) plus linezolid (500 mg/L) was the best drug combination and its efficacy was superior to conventional regimens, not only in prolonging infected fly survival but also against M. abscessus colonization and dissemination. This D. melanogaster-M. abscessus infection/curing methodology may be useful for the rapid evaluation of potential drug candidates. In addition, new combinations using tigecycline and linezolid should be considered as possible next-generation combination therapies to be assessed in higher organisms. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Catanionic drug-derivative nano-objects constructed by chlorambucil and its derivative for efficient leukaemia therapy.

    Science.gov (United States)

    Ji, Xiaoqing; Shi, Chunhuan; Li, Nuannuan; Wang, Kaiming; Li, Zhonghao; Luan, Yuxia

    2015-12-01

    A new carrier-free catanionic drug-derivative nano-object strategy is developed for leukaemia therapy. The as-prepared drug-derivative nano-objects are formed by ionic pairs of hydrophobic anticancer drug chlorambucil (CLB) and its derivative N-(2-Amino-ethyl)-4-{4-[bis-(2-chloro-ethyl)-amino]-phenyl}-butyramide (CLBM). The designed drug delivery system has the advantage of 100% drug content without additional carrier materials. The ionic pairs are formed by proton exchange between CLB and CLBM. Due to the amphiphilicity of the ionic pairs, they can assemble into well-defined drug-derivative (CLB-CLBM) nano-objects. Series of techniques such as transmission electron microscopy (TEM), dynamic light scattering (DLS) and electrical conductivity are used to investigate the property of the solution and aggregation behaviour of as-prepared drug-derivative ionic pairs. In vitro drug release study of the as-prepared nano-objects shows their prolonged drug release behavior. Specifically, in vitro cytotoxicity results of these nano-objects show obviously higher cytotoxicity, which is promising for clinical efficacy. This study may pave the way for the fabrication of carrier-free drug delivery system with efficient cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering.

    Science.gov (United States)

    Busuttil, Francesca; Rahim, Ahad A; Phillips, James B

    2017-02-15

    Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.

  1. Duration of dual antiplatelet therapy after implantation of drug-eluting stents.

    Science.gov (United States)

    Park, Seung-Jung; Park, Duk-Woo; Kim, Young-Hak; Kang, Soo-Jin; Lee, Seung-Whan; Lee, Cheol Whan; Han, Ki-Hoon; Park, Seong-Wook; Yun, Sung-Cheol; Lee, Sang-Gon; Rha, Seung-Woon; Seong, In-Whan; Jeong, Myung-Ho; Hur, Seung-Ho; Lee, Nae-Hee; Yoon, Junghan; Yang, Joo-Young; Lee, Bong-Ki; Choi, Young-Jin; Chung, Wook-Sung; Lim, Do-Sun; Cheong, Sang-Sig; Kim, Kee-Sik; Chae, Jei Keon; Nah, Deuk-Young; Jeon, Doo-Soo; Seung, Ki Bae; Jang, Jae-Sik; Park, Hun Sik; Lee, Keun

    2010-04-15

    The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established. In two trials, we randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis. The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06). The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.) 2010 Massachusetts Medical Society

  2. Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

    Science.gov (United States)

    Talukdar, Yahfi

    Healing critical sized bone defects has been a challenge that led to innovations in tissue engineering scaffolds and biomechanical stimulations that enhance tissue regeneration. Carbon nanocomposite scaffolds have gained interest due to their enhanced mechanical properties. However, these scaffolds are only osteoconductive and not osteoinductive. Stimulating regeneration of bone tissue, osteoinductivity, has therefore been a subject of intense research. We propose the use of carbon nanoparticle enhanced photoacoustic (PA) stimulation to promote and enhance tissue regeneration in bone tissue-engineering scaffolds. In this study we test the feasibility of using carbon nanoparticles and PA for in vivo tissue engineering applications. To this end, we investigate 1) the effect of carbon nanoparticles, such as graphene oxide nanoplatelets (GONP), graphene oxide nano ribbons (GONR) and graphene nano onions (GNO), in vitro on mesenchymal stem cells (MSC), which are crucial for bone regeneration; 2) the use of PA imaging to detect and monitor tissue engineering scaffolds in vivo; and 3) we demonstrate the potential of carbon nanoparticle enhanced PA stimulation to promote tissue regeneration and healing in an in vivo rat fracture model. The results from these studies demonstrate that carbon nanoparticles such as GNOP, GONR and GNO do not affect viability or differentiation of MSCs and could potentially be used in vivo for tissue engineering applications. Furthermore, PA imaging can be used to detect and longitudinally monitor subcutaneously implanted carbon nanotubes incorporated polymeric nanocomposites in vivo. Oxygen saturation data from PA imaging could also be used as an indicator for tissue regeneration within the scaffolds. Lastly, we demonstrate that daily stimulation with carbon nanoparticle enhanced PA increases bone fracture healing. Rats stimulated for 10 minutes daily for two weeks showed 3 times higher new cortical bone BV/TV and 1.8 times bone mineral density

  3. Drug-device combination products in the twenty-first century: epinephrine auto-injector development using human factors engineering.

    Science.gov (United States)

    Edwards, Eric S; Edwards, Evan T; Simons, F Estelle R; North, Robert

    2015-05-01

    The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration. A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program. For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.

  4. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy.

    Science.gov (United States)

    Unterweger, Harald; Subatzus, Daniel; Tietze, Rainer; Janko, Christina; Poettler, Marina; Stiegelschmitt, Alfons; Schuster, Matthias; Maake, Caroline; Boccaccini, Aldo R; Alexiou, Christoph

    2015-01-01

    Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55-85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5-5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs' targeting abilities with hypericin's phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer.

  5. QTC INTERVAL DURATION CLASS AND DRUG THERAPY OF PATIENCE IN A FIRST YEAR AFTER PACEMAKER IMPLANTATION

    Directory of Open Access Journals (Sweden)

    M. S. Brynza

    2016-12-01

    Full Text Available 49 patients (28 female, 21 male with implanted DDD/DDDR, VVI/VVIR and CRT pacemakers are investigated. Purpose frequency and dose rate of anticoagulants, antiplatelet agents, direct thrombin inhibitors, cardiac glycosides, amiodarone; ivabradine, diuretics, aldosterone antagonists, beta-adrenergic blockers, calcium channel blockers, angiotensin-converting enzyme (ACE inhibitors, angiotensin II receptor blockers (ARBs, statins were evaluated before, in acute postoperative period (3–5 days, 6 months and 1 year after pacemaker implantation. Patients were divided into classes 1 (normal QTc (320–440 ms – 24 (49 % patients and 2 (long QTc (> 440 msec – 25 (51 % patients of QTc interval duration. To process the data using standard statistical procedures using Microsoft Excel. It was more often prescriptions of new anticoagulants, beta-adrenergic blockers, ARBs, statins to patients in the first year after pacemaker implantation. QTc interval duration lengthening was associated with a greater purpose frequency and doses of amiodarone, diuretics, beta-adrenergic blockers, ACE inhibitors, ARBs and statins. Patients with implanted pacemaker need individualized drug therapy according to QTc interval duration, in particular, enhancing antiischemic, antihypertensive, antiarrhythmic therapy and therapy of chronic heart failure in patients with QTc interval duration lengthening.

  6. Drug design with Cdc7 kinase: a potential novel cancer therapy target

    Directory of Open Access Journals (Sweden)

    Masaaki Sawa

    2008-11-01

    Full Text Available Masaaki Sawa1, Hisao Masai21Carna Biosciences, Inc., Kobe, Japan; 2Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAbstract: Identification of novel molecular targets is critical in development of new and efficient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not significantly affect viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC50 of less than 10 nM have been identified, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.Keywords: Cdc7 kinase, cell cycle, replication fork, genome stability, DNA damages, ATP-binding pocket, kinase inhibitor

  7. Concurrent anti-vascular therapy and chemotherapy in solid tumors using drug-loaded acoustic nanodroplet vaporization.

    Science.gov (United States)

    Ho, Yi-Ju; Yeh, Chih-Kuang

    2017-02-01

    Drug-loaded nanodroplets (NDs) can be converted into gas bubbles through ultrasound (US) stimulation, termed acoustic droplet vaporization (ADV), which provides a potential strategy to simultaneously induce vascular disruption and release drugs for combined physical anti-vascular therapy and chemotherapy. Doxorubicin-loaded NDs (DOX-NDs) with a mean size of 214nm containing 2.48mg DOX/mL were used in this study. High-speed images displayed bubble formation and cell debris, demonstrating the reduction in cell viability after ADV. Intravital imaging provided direct visualization of disrupted tumor vessels (vessel size chemotherapy with DOX-NDs vaporization promotes uniform treatment to improve therapeutic efficacy. Tumor vasculature plays an important role for tumor cell proliferation by transporting oxygen and nutrients. Previous studies combined anti-vascular therapy and drug release to inhibit tumor growth by ultrasound-stimulated microbubble destruction or acoustic droplet vaporization. Although the efficacy of combined therapy has been demonstrated; the relative spatial distribution of vascular disruption, drug delivery, and accompanied immune responses within solid tumors was not discussed clearly. Herein, our study used drug-loaded nanodroplets to combined physical anti-vascular and chemical therapy. The in vitro cytotoxicity, intravital imaging, and histological assessment were used to evaluate the temporal and spatial cooperation between physical and chemical effect. These results revealed some evidences for complementary action to explain the high efficacy of tumor inhibition by combined therapy. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Cell Therapies for Heart Function Recovery: Focus on Myocardial Tissue Engineering and Nanotechnologies

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Giraud

    2012-01-01

    Full Text Available Cell therapies have gained increasing interest and developed in several approaches related to the treatment of damaged myocardium. The results of multiple clinical trials have already been reported, almost exclusively involving the direct injection of stem cells. It has, however, been postulated that the efficiency of injected cells could possibly be hindered by the mechanical trauma due to the injection and their low survival in the hostile environment. It has indeed been demonstrated that cell mortality due to the injection approaches 90%. Major issues still need to be resolved and bed-to-bench followup is paramount to foster clinical implementations. The tissue engineering approach thus constitutes an attractive alternative since it provides the opportunity to deliver a large number of cells that are already organized in an extracellular matrix. Recent laboratory reports confirmed the interest of this approach and already encouraged a few groups to investigate it in clinical studies. We discuss current knowledge regarding engineered tissue for myocardial repair or replacement and in particular the recent implementation of nanotechnological approaches.

  9. Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal?

    Science.gov (United States)

    Clavreul, Anne; Pourbaghi-Masouleh, Milad; Roger, Emilie; Lautram, Nolwenn; Montero-Menei, Claudia N; Menei, Philippe

    2017-09-29

    Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) is of limited efficacy. Innovative anticancer drugs targeting both tumor cells and angiogenesis are urgently required, together with effective systems for their delivery to the brain. We assessed the ability of human mesenchymal stromal cells (MSCs) to uptake the multikinase inhibitor, sorafenib (SFN), and to carry this drug to a brain tumor following intranasal administration. MSCs were primed with SFN and drug content and release were quantified by analytical chemistry techniques. The ability of SFN-primed MSCs to inhibit the survival of the human U87MG GB cell line and endothelial cells was assessed in in vitro assays. These cells were then administered intranasally to nude mice bearing intracerebral U87MG xenografts. Their effect on tumor growth and angiogenesis was evaluated by magnetic resonance imaging and immunofluorescence analyses, and was compared with the intranasal administration of unprimed MSCs or SFN alone. MSCs took up about 9 pg SFN per cell, with no effect on viability, and were able to release 60% of the primed drug. The cytostatic activity of the released SFN was entirely conserved, resulting in a significant inhibition of U87MG and endothelial cell survival in vitro. Two intranasal administrations of SFN-primed MSCs in U87MG-bearing mice resulted in lower levels of tumor angiogenesis than the injection of unprimed MSCs or SFN alone, but had no effect on tumor volume. We also observed an increase in the proportion of small intratumoral vessels in animals treated with unprimed MSCs; this effect being abolished if the MSCs were primed with SFN. We show the potential of MSCs to carry SFN to brain tumors following an intranasal administration. However, the therapeutic effect is modest probably due to the pro

  10. Cardiac Arrhythmias in Patients with Chronic Kidney Disease: Implications of Renal Failure for Antiarrhythmic Drug Therapy.

    Science.gov (United States)

    Potpara, Tatjana S; Jokic, Vera; Dagres, Nikolaos; Marin, Francisco; Prostran, Milica S; Blomstrom-Lundqvist, Carina; Lip, Gregory Y H

    2016-01-01

    The kidney has numerous complex interactions with the heart, including shared risk factors (e.g., hypertension, dyslipidemia, etc.) and mutual amplification of morbidity and mortality. Both cardiovascular diseases and chronic kidney disease (CKD) may cause various alterations in cardiovascular system, metabolic homeostasis and autonomic nervous system that may facilitate the occurrence of cardiac arrhythmias. Also, pre-existent or incident cardiac arrhythmias such as atrial fibrillation (AF) may accelerate the progression of CKD. Patients with CKD may experience various cardiac rhythm disturbances including sudden cardiac death. Contemporary management of cardiac arrhythmias includes the use of antiarrhythmic drugs (AADs), catheter ablation and cardiac implantable electronic devices (CIEDs). Importantly, AADs are not used only as the principal treatment strategy, but also as an adjunct therapy in combination with CIEDs, to facilitate their effects or to minimize inappropriate device activation in selected patients. Along with their principal antiarrhythmic effect, AADs may also induce cardiac arrhythmias and the risk for such proarrhythmic effect(s) is particularly increased in patients with reduced left ventricular systolic function or in the setting of electrolyte imbalance. Moreover, CKD itself can induce profound alterations in the pharmacokinetics and pharmacodynamics of many drugs including AADs, thus facilitating the drug accumulation and increased exposure. Hence, the use of AADs in patients with CKD may be challenging. In this review article, we provide an overview of the characteristics of arrhythmogenesis in patients with CKD with special emphasis on the complexity of pharmacokinetics and risk for proarrhythmias when using AADs in patients with cardiac arrhythmias and CKD.

  11. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    Science.gov (United States)

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288

  12. Smart tetrazole-based antibacterial nanoparticles as multifunctional drug carriers for cancer combination therapy.

    Science.gov (United States)

    Zakerzadeh, Elham; Salehi, Roya; Mahkam, Mehrdad

    2017-12-01

    Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal, and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, 1 H NMR, FESEM-EDX, and TGA analyzes and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi. Then, the pH-responsive manner of both nanocomposites was proved by checking their release profiles at pH of the physiological environment (pH 7.4) and pH of tumor tissues (mildly acidic). Finally, the potential antitumoral activity of these nanocomposite systems against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The results demonstrated that the novel developed nanocomposites not only meet our expectations about simultaneous release of two anticancer drugs according to the predicted profile but also showed antibacterial and anticancer properties in vitro experimental. Moreover, it was proved that these carriers have tremendous potential in multifunctional drug delivery in cancer therapy.

  13. Laser Printing of PCL/Progesterone Tablets for Drug Delivery Applications in Hormone Cancer Therapy

    Science.gov (United States)

    Salmoria, G. V.; Klauss, P.; Kanis, L. A.

    2017-09-01

    In this study, polycaprolactone (PCL) and progesterone (PG) tablets were produced by selective laser sintering (SLS) using different particle sizes and laser energy. The sintered PCL/PG tablets presented uniform morphology, coalescence of particles and interconnected pores distributed in the polymeric matrix. The EDS analysis confirmed the presence of progesterone recrystallized on the surface of the porous PCL matrix. The crystallinity values for the PCL/PG tablets were lower than that for the pure PCL, suggesting the interaction of components at the molecular level. The PCL/PG tablets fabricated with small particles and high laser energy presented a higher value for the flexural modulus compared with the other specimens. The glass transition temperature (Tg) was -37 °C for the PCL/PG tablet with a high degree of sintering. The fatigue test showed that the PCL/PG blend tablets have high fatigue strength. The drug release mechanism of all tablets studied followed a zero-order kinetics, and drug release rates were dependent on sintering degree and, consequently, on matrix erosion, showing a potential application to controlled drug delivery in hormone cancer therapy.

  14. Dialectical behavior therapy for patients with borderline personality disorder and drug-dependence.

    Science.gov (United States)

    Linehan, M M; Schmidt, H; Dimeff, L A; Craft, J C; Kanter, J; Comtois, K A

    1999-01-01

    A randomized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy (DBT), an effective cognitive-behavioral treatment for suicidal individuals with borderline personality disorder (BPD), would also be effective for drug-dependent women with BPD when compared with treatment-as-usual (TAU) in the community. Subjects were randomly assigned to either DBT or TAU for a year of treatment. Subjects were assessed at 4, 8, and 12 months, and at a 16-month follow-up. Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow-up than did subjects assigned to TAU. DBT also maintained subjects in treatment better than did TAU, and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow-up than did those assigned to TAU. DBT has been shown to be more effective than treatment-as-usual in treating drug abuse in this study, providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems.

  15. Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo

    Science.gov (United States)

    Khurana, Mamta; Moriyama, Eduardo H.; Mariampillai, Adrian; Samkoe, Kimberley; Cramb, David; Wilson, Brian C.

    2009-11-01

    As part of an ongoing program to develop two-photon (2-γ) photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-γ and 2-γ activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-γ cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-γ PDT of AMD.

  16. The potential application of photodynamic therapy in drug-resistant tuberculosis.

    Science.gov (United States)

    Chang, Ji-Eun; Oak, Chul-Ho; Sung, Nackmoon; Jheon, Sanghoon

    2015-09-01

    Tuberculosis (TB) is an infectious bacterial disease that has historically created a high global health burden. Unfortunately, the emergence of drug-resistant TB (DR-TB), which includes multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), has greatly affected the treatment of TB. Anti-TB chemotherapy drugs are classified into five groups to facilitate application of effective guidelines for the treatment regimen. However, chemotherapy has a limited ability to treat DR-TB, and therefore a novel alternative treatment for DR-TB is required. In this review, we focused on photodynamic therapy (PDT) as potential treatment for DR-TB. PDT is a widely used cancer treatment that combines photosensitizers and harmless laser light to produce reactive oxygen species that selectively damage the target cells. Initially, PDT was originally developed to target pathogenic microorganisms but fell into disuse because of adverse reactions. Recently, photodynamic antimicrobial chemotherapy is attracting attention again as an alternative treatment for bacterial infections. In our previous study, we suggested that PDT could be a novel option to treat MDR- and XDR-TB in vitro. Despite the limited previous studies regarding PDT in TB models, fast-developing bronchoscopic technologies and clinician experience will soon facilitate the clinical application of safe and minimally invasive PDT for TB. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Survival of patients discharged after acute myocardial infarction and evidence-based drug therapy.

    Science.gov (United States)

    Gouya, Ghazaleh; Reichardt, Berthold; Ohrenberger, Gerald; Wolzt, Michael

    2007-01-01

    There is consensus that patients should be treated with antiplatelet agents, beta-blockers, ACE-inhibitors/ARBs, and lipid lowering drugs for secondary prevention after acute myocardial infarction (AMI), but this evidence-based pharmacotherapy is underutilized. A quality improvement program was conducted in the Austrian county of Burgenland to emphasize the importance of cardiovascular drug therapy at hospital discharge in patients with AMI. In this prospective cohort study 250 members of a regional health insurance company, Burgenländische Gebietskrankenkasse (BGKK), with AMI during the year 2003 were identified using BGKK database. Discharge prescriptions and pharmacy reimbursement data of all included patients were determined. Overall prescription rate for patients discharged from hospital after AMI (n = 207) was 86% for platelet aggregation inhibitors, 77% for ACE-inhibitors or ARBs, 72% for beta-blockers, and 68% for a lipid lowering agent including statins. The all-cause mortality rate during a mean follow-up period of 552 days was 20%. Hazard ratio (HR) for death of patients with maximum 2 medications vs. those receiving 3 or 4 medications was 2.23 (95% CI: 1.19-4.18; p = 0.012). These data demonstrate that use of evidence-based drug treatment for prevention of mortality in patients with AMI is associated with risk reduction and survival benefit. Continuous quality improvement initiatives serve to improve outcome after AMI.

  18. Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery.

    Science.gov (United States)

    Parodi, Alessandro; Molinaro, Roberto; Sushnitha, Manuela; Evangelopoulos, Michael; Martinez, Jonathan O; Arrighetti, Noemi; Corbo, Claudia; Tasciotti, Ennio

    2017-12-01

    The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles' surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles. Copyright © 2017. Published by Elsevier Ltd.

  19. Biotechnology and genetic engineering in the new drug development. Part I. DNA technology and recombinant proteins.

    Science.gov (United States)

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Pharmaceutical biotechnology has a long tradition and is rooted in the last century, first exemplified by penicillin and streptomycin as low molecular weight biosynthetic compounds. Today, pharmaceutical biotechnology still has its fundamentals in fermentation and bioprocessing, but the paradigmatic change affected by biotechnology and pharmaceutical sciences has led to an updated definition. The biotechnology revolution redrew the research, development, production and even marketing processes of drugs. Powerful new instruments and biotechnology related scientific disciplines (genomics, proteomics) make it possible to examine and exploit the behavior of proteins and molecules. Recombinant DNA (rDNA) technologies (genetic, protein, and metabolic engineering) allow the production of a wide range of peptides, proteins, and biochemicals from naturally nonproducing cells. This technology, now approximately 25 years old, is becoming one of the most important technologies developed in the 20(th) century. Pharmaceutical products and industrial enzymes were the first biotech products on the world market made by means of rDNA. Despite important advances regarding rDNA applications in mammalian cells, yeasts still represent attractive hosts for the production of heterologous proteins. In this review we describe these processes.

  20. 3D Printing technology over a drug delivery for tissue engineering.

    Science.gov (United States)

    Lee, Jin Woo; Cho, Dong-Woo

    2015-01-01

    Many researchers have attempted to use computer-aided design (CAD) and computer-aided manufacturing (CAM) to realize a scaffold that provides a three-dimensional (3D) environment for regeneration of tissues and organs. As a result, several 3D printing technologies, including stereolithography, deposition modeling, inkjet-based printing and selective laser sintering have been developed. Because these 3D printing technologies use computers for design and fabrication, and they can fabricate 3D scaffolds as designed; as a consequence, they can be standardized. Growth of target tissues and organs requires the presence of appropriate growth factors, so fabrication of 3Dscaffold systems that release these biomolecules has been explored. A drug delivery system (DDS) that administrates a pharmaceutical compound to achieve a therapeutic effect in cells, animals and humans is a key technology that delivers biomolecules without side effects caused by excessive doses. 3D printing technologies and DDSs have been assembled successfully, so new possibilities for improved tissue regeneration have been suggested. If the interaction between cells and scaffold system with biomolecules can be understood and controlled, and if an optimal 3D tissue regenerating environment is realized, 3D printing technologies will become an important aspect of tissue engineering research in the near future.

  1. 3D Printing of Calcium Phosphate Ceramics for Bone Tissue Engineering and Drug Delivery.

    Science.gov (United States)

    Trombetta, Ryan; Inzana, Jason A; Schwarz, Edward M; Kates, Stephen L; Awad, Hani A

    2017-01-01

    Additive manufacturing, also known as 3D printing, has emerged over the past 3 decades as a disruptive technology for rapid prototyping and manufacturing. Vat polymerization, powder bed fusion, material extrusion, and binder jetting are distinct technologies of additive manufacturing, which have been used in a wide variety of fields, including biomedical research and tissue engineering. The ability to print biocompatible, patient-specific geometries with controlled macro- and micro-pores, and to incorporate cells, drugs and proteins has made 3D-printing ideal for orthopaedic applications, such as bone grafting. Herein, we performed a systematic review examining the fabrication of calcium phosphate (CaP) ceramics by 3D printing, their biocompatibility in vitro, and their bone regenerative potential in vivo, as well as their use in localized delivery of bioactive molecules or cells. Understanding the advantages and limitations of the different 3D printing approaches, CaP materials, and bioactive additives through critical evaluation of in vitro and in vivo evidence of efficacy is essential for developing new classes of bone graft substitutes that can perform as well as autografts and allografts or even surpass the performance of these clinical standards.

  2. Electroconvulsive therapy in drug resistant neuroleptic malignant syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yousefi A

    2010-02-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* 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:0in; mso-para-margin-bottom:.0001pt; 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:Arial; mso-bidi-theme-font:minor-bidi;} Background: Neuroleptic malignant syndrome is an idiosyncratic and potentially fatal reaction to neuroleptic drugs and is characterized by fever, muscular rigidity, altered mental status, autonomic dysfunction, elevated serum CPK and leucocytosis Neuroleptic malignant syndrome is treated with dantrolene, bromocriptin, amantadin and electroconvulsive therapy."n"nCase: A 22 years old, schizophrenic female was refered to the Emergency ward of Roozbeh hospital in Tehran, Iran in December 2008 with aggression, impulsivity, and reduced sleep. After injection of haloperidol, the patient developed a high grade fever, diaphoresis and muscular stiffness. She was diagnosed as neuroleptic malignant syndrome and the treatment with dantrolen, bromocriptin and amantadin initiated. Although fever subsided, other signs continued, therefore we applied electroconvulsive therapy to this case."n"nConclusion: Due to excellent response of the patient to electroconvulsive therapy and the rare reports of electroconvulsive therapy in neuroleptic malignant syndrome in the Iranian population, this case may lead to develop studies for further investigations of this issue.

  3. Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes for Controlled, Localized Synthesis of Therapeutics.

    Science.gov (United States)

    Chandrawati, Rona; Olesen, Morten T J; Marini, Thatiane C C; Bisra, Gurpal; Guex, Anne Géraldine; de Oliveira, Marcelo G; Zelikin, Alexander N; Stevens, Molly M

    2017-09-01

    Enzyme prodrug therapy (EPT) enables localized conversion of inert prodrugs to active drugs by enzymes. Performance of EPT necessitates that the enzyme remains active throughout the time frame of the envisioned therapeutic application. β-glucuronidase is an enzyme with historically validated performance in EPT, however it retains its activity in biomaterials for an insufficiently long period of time, typically not exceeding 7 d. Herein, the encapsulation of β-glucuronidase in liposomal subcompartments within poly(vinyl alcohol) electrospun fibers is reported, leading to the assembly of biocatalytically active materials with activity of the enzyme sustained over at least seven weeks. It is further shown that liposomes provide the highly beneficial stabilization of the enzyme when incubated in cell culture media. The assembled biocatalytic materials successfully produce antiproliferative drugs (SN-38) using externally administered prodrugs (SN-38-glucuronide) and effectively suppress cell proliferation, with envisioned utility in the design of cardiovascular grafts. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Metal complexes in cancer therapy – an update from drug design perspective

    Directory of Open Access Journals (Sweden)

    Ndagi U

    2017-03-01

    Full Text Available Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective

  5. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Berg, Lise Charlotte; Betts, Dean H.

    2009-01-01

    This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds......, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent...... factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently...

  6. Antiepileptic drug therapy and recommendations for withdrawal in patients with seizures and epilepsy due to neurocysticercosis.

    Science.gov (United States)

    Bustos, Javier A; García, Héctor H; Del Brutto, Oscar H

    2016-09-01

    Neurocysticercosis (NCC) is a leading causes of secondary epilepsy worldwide. There is increasing evidence on the epileptogenic role of NCC, and the presence of edema, calcified scars, gliosis and hippocampal sclerosis support this phenomenon. We summarized principles of antiepileptic drug (AED) therapy as well as risk factors associated with seizure recurrence after AED withdrawal in patients with NCC. Expert commentary: First-line AED monotherapy is effective as a standard approach to control seizures in most NCC patients. Risks and benefits of AED withdrawal have not been systematically studied, and this decision must be individualized. However, a seizure-free period of at least two years seem prudent before attempting withdrawal. Risk factors for seizure recurrence after AED withdrawal include a history of status epilepticus, poor seizure control during treatment, neuroimaging evidence of perilesional gliosis, hippocampal sclerosis and calcified lesions, as well as persistence of paroxysmal activity in the EEG.

  7. Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use

    DEFF Research Database (Denmark)

    Ytting, Henriette; Larsen, Fin Stolze

    2015-01-01

    OBJECTIVE: Not all patients with autoimmune hepatitis (AIH) respond to standard medical therapy with corticosteroids and azathioprine. Such patients may develop end-stage liver disease with poor prognosis unless transplantation is considered. Alternatively, the introduction of new therapeutic...... strategies could potentially ameliorate deterioration of liver function. Patients in our tertiary center were selected for everolimus therapy when exhibiting nonresponse or intolerance to combinations of the standard and empirical drugs in use (e.g., mycophenolate mofetil, calcineurin inhibitors [CNIs]). We...

  8. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Preparation and characterization of maghemite nanoparticles from mild steel for magnetically guided drug therapy.

    Science.gov (United States)

    Kumar, Nitesh; Kulkarni, Kaustubh; Behera, Laxmidhar; Verma, Vivek

    2017-08-01

    Maghemite (γ-Fe 2 O 3) nanoparticles for therapeutic applications are prepared from mild steel but the existing synthesis technique is very cumbersome. The entire process takes around 100 days with multiple steps which lack proper understanding. In the current work, maghemite nanoparticles of cuboidal and spheroidal morphologies were prepared from mild steel chips by a novel cost effective oil reduction technique for magnetically guided intravascular drug delivery. The technique developed in this work yields isometric sized γ-Fe 2 O 3 nanoparticles in 6 h with higher saturation magnetization as compared to the existing similar solid state synthesis route. Mass and heat flow kinetics during the heating and quenching steps were studied with the help of Finite element simulations. Qualitative and quantitative analysis of the γ-Fe 2 O 3 phase is performed with the help of x-ray diffraction, transmission electron microscope and x-ray photoelectron spectroscopy. Mechanism for the α-Fe 2 O 3 (haematite) to γ-Fe 2 O 3 (maghemite) phase evolution during the synthesis process is also investigated. Maghemite (γ-Fe2O3) nanoparticles were prepared bya novel cost effective oil reduction technique as mentioned below in the figure. The raw materials included mild steel chips which is one of the most abundant engineering materials. These particles can be used as ideal nanocarriers for targeted drug delivery through the vascular network.

  10. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.

    Science.gov (United States)

    Tian, Tian; Zhang, Hui-Xin; He, Chun-Peng; Fan, Song; Zhu, Yan-Liang; Qi, Cui; Huang, Ning-Ping; Xiao, Zhong-Dang; Lu, Zu-Hong; Tannous, Bakhos A; Gao, Jun

    2018-01-01

    The safe and effective delivery of drugs is a major obstacle in the treatment of ischemic stroke. Exosomes hold great promise as an endogenous drug delivery nanosystem for the treatment of cerebral ischemia given their unique properties, including low immunogenicity, innate stability, high delivery efficiency, and ability to cross the blood-brain barrier (BBB). However, exosome insufficient targeting capability limits their clinical applications. In this study, the c(RGDyK) peptide has been conjugated to the exosome surface by an easy, rapid, and bio-orthogonal chemistry. In the transient middle cerebral artery occlusion (MCAO) mice model, The engineered c(RGDyK)-conjugated exosomes (cRGD-Exo) target the lesion region of the ischemic brain after intravenous administration. Furthermore, curcumin has been loaded onto the cRGD-Exo, and administration of these exosomes has resulted in a strong suppression of the inflammatory response and cellular apoptosis in the lesion region. The results suggest a targeting delivery vehicle for ischemic brain based on exosomes and provide a strategy for the rapid and large-scale production of functionalized exosomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Krentz Hartmut B

    2010-06-01

    Full Text Available Abstract Background Anti-epileptic drugs (AEDs are frequently prescribed to persons with HIV/AIDS receiving combination antiretroviral therapy (cART although the extent of AED use and their interactions with cART are uncertain. Herein, AED usage, associated toxicities and immune consequences were investigated. Methods HIV replication was analysed in proliferating human T cells during AED exposure. Patients receiving AEDs in a geographically-based HIV care program were assessed using clinical and laboratory variables in addition to assessing AED indication, type, and cumulative exposures. Results Valproate suppressed proliferation in vitro of both HIV-infected and uninfected T cells (p 0.05 but AED exposures did not affect HIV production in vitro. Among 1345 HIV/AIDS persons in active care between 2001 and 2007, 169 individuals were exposed to AEDs for the following indications: peripheral neuropathy/neuropathic pain (60%, seizure/epilepsy (24%, mood disorder (13% and movement disorder (2%. The most frequently prescribed AEDs were calcium channel blockers (gabapentin/pregabalin, followed by sodium channel blockers (phenytoin, carbamazepine, lamotrigine and valproate. In a nested cohort of 55 AED-treated patients receiving cART and aviremic, chronic exposure to sodium and calcium channel blocking AEDs was associated with increased CD4+ T cell levels (p 0.05 with no change in CD8+ T cell levels over 12 months from the beginning of AED therapy. Conclusions AEDs were prescribed for multiple indications without major adverse effects in this population but immune status in patients receiving sodium or calcium channel blocking drugs was improved.

  12. WE-EF-BRA-09: Microbeam Radiation Therapy Enhances Tumor Drug Uptake of PEGylated Liposomal Doxorubicin (PLD) in a Triple Negative Breast Cancer GEM Model

    Energy Technology Data Exchange (ETDEWEB)

    Chang, SX; Madden, AJ; Rivera, JN; Santos, CM; Hunter, LM; Darr, DB; Zamboni, WC [UNC School of Medicine, Chapel Hill, NC (United States)

    2015-06-15

    Purpose: Overcoming low anti-cancer drug uptake in tumors is a key challenge limiting its clinical use. We propose to enhance the drug delivery using upfront Microbeam Radiation Therapy (MRT). MRT is a preclinical cancer therapy that utilizes microplanar beams to deliver spatially oscillating planes of high and low doses. Animal studies have demonstrated that ultrahigh dose (100s Gy) MRT eradicates tumors without damaging the function of normal tissue exposed to the same radiation. Our previous study indicated that MRT induces intense angiogenesis in tumor rim and surrounding normal tissue 1–2 days post radiation. We hypothesize that the tumor microenvironment modulation induced by MRT may enhance carrier-mediated agent drug delivery to tumors with inherent poor drug uptake. We thus investigated MRT-induced pharmacokinetics (PK) of PEGylated liposomal doxorubicin (PLD), a nano-scale doxorubicin, in T11 genetically engineered mouse model of triple negative breast cancer. Methods: A research irradiator (160kVp, RadSource Technologies) with a customized collimator was used to produce the MRT microbeam of in average 390µm width and 1190µm peak-to-peak distance. The peak dose rate of 1–2Gy/min. Dosimetry is by EBT3 film cross-calibrated with ion chamber at large fields. All mice were administered PLD at 6mg/kg IV x1 at 16h post MRT and sacrificed at 5min, 6h, 24h, and 96h post PLD administration (n=3 or 4 per group). Results: The MRT(28Gy)+PLD group mice had a total doxorubicin tumor concentration (area-under-the concentration-curve, AUC) of 206,040ng/mL•h, 3.71 times the concentration of the PLD-alone group. The MRT(34Gy)+PLD group had a higher mean total doxorubicin concentration in tumor (20,779ng/ml) than the MRT(28Gy)+PLD group (10,665ng/ml). Conclusion: Our preliminary results indicate that microbeam radiation therapy (MRT) can enhance nano-scale anti-cancer drug delivery to tumors approximately 4-fold. The exact working mechanism, the comparison with

  13. Molecular, cellular, and tissue engineering

    CERN Document Server

    Bronzino, Joseph D

    2015-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

  14. The Knowledge Level of Hypertension Patients for Drug Therapy in the Primary Health Care of Malang

    Directory of Open Access Journals (Sweden)

    Hananditia R. Pramestutie

    2016-04-01

    Full Text Available Hypertension is a persistent blood pressure in which systolic pressure ≥140 mmHg and diastolic pressure ≥90 mmHg. The knowledge that should be owned by patients with hypertension is the meaning, causes, symptoms and treatment of hypertension. This knowledge is important to support the success of hypertension therapy. The aim of this research was to determine the knowledge level of hypertension patients about their drug therapy in the primary health care of Malang. This research used observational study methods. The selection of the patients and the primary health care was done using non-random sampling technique (purposive sampling. The subject who meet the inclusion criteria were involved. The result of this study revealed that the patients with hypertension who have a sufficient level of knowledge were 69 respondents (72,63%. Patients who have a good criteria were 26 respondents (27,3763%. There is no patient with low level of knowledge in this research. The conclusion from this study is most patients with hypertension in Primary Health Care Malang have enough knowledge about their treatment.

  15. Emerging Glycolysis Targeting and Drug Discovery from Chinese Medicine in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Zhiyu Wang

    2012-01-01

    Full Text Available Molecular-targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells have different metabolic properties from normal cells. Normal cells mostly rely upon the process of mitochondrial oxidative phosphorylation to produce energy whereas cancer cells have developed an altered metabolism that allows them to sustain higher proliferation rates. Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM is recognized as a valuable source for seeking bioactive anticancer compounds. A great progress has been made to identify active compounds from herbal medicine targeting on glycolysis for cancer treatment. Herein, we provide an overall picture of the current understanding of the molecular targets in the cancer glycolytic pathway and reviewed active compounds from Chinese herbal medicine with the potentials to inhibit the metabolic targets for cancer treatment. Combination of TCM with conventional therapies will provide an attractive strategy for improving clinical outcome in cancer treatment.

  16. The New Era of Drug Therapy for Obesity: The Evidence and the Expectations.

    Science.gov (United States)

    Jones, Ben J; Bloom, Stephen R

    2015-06-01

    There is an urgent need for effective pharmacological therapies to help tackle the growing obesity epidemic and the healthcare crisis it poses. The past 3 years have seen approval of a number of novel anti-obesity drugs. The majority of these influence hypothalamic appetite pathways via dopaminergic or serotoninergic signalling. Some are combination therapies, allowing lower doses to minimize the potential for off-target effects. An alternative approach is to mimic endogenous satiety signals using long-lasting forms of peripheral appetite-suppressing hormones. There is also considerable interest in targeting thermogenesis by brown adipose tissue to increase resting energy expenditure. Obesity pharmacotherapy has seen several false dawns, but improved understanding of the pathways regulating energy balance, and better-designed trials, give many greater confidence that recently approved agents will be both efficacious and safe. Nevertheless, a number of issues from preclinical and clinical development continue to attract debate, and additional large-scale trials are still required to address areas of uncertainty.

  17. Increasing Access to Subsidized Artemisinin-based Combination Therapy through Accredited Drug Dispensing Outlets in Tanzania

    Directory of Open Access Journals (Sweden)

    Gabra Michael

    2011-06-01

    Full Text Available Abstract Background In Tanzania, many people seek malaria treatment from retail drug sellers. The National Malaria Control Program identified the accredited drug dispensing outlet (ADDO program as a private sector mechanism to supplement the distribution of subsidized artemisinin-based combination therapies (ACTs from public facilities and increase access to the first-line antimalarial in rural and underserved areas. The ADDO program strengthens private sector pharmaceutical services by improving regulatory and supervisory support, dispenser training, and record keeping practices. Methods The government's pilot program made subsidized ACTs available through ADDOs in 10 districts in the Morogoro and Ruvuma regions, covering about 2.9 million people. The program established a supply of subsidized ACTs, created a price system with a cost recovery plan, developed a plan to distribute the subsidized products to the ADDOs, trained dispensers, and strengthened the adverse drug reactions reporting system. As part of the evaluation, 448 ADDO dispensers brought their records to central locations for analysis, representing nearly 70% of ADDOs operating in the two regions. ADDO drug register data were available from July 2007-June 2008 for Morogoro and from July 2007-September 2008 for Ruvuma. This intervention was implemented from 2007-2008. Results During the pilot, over 300,000 people received treatment for malaria at the 448 ADDOs. The percentage of ADDOs that dispensed at least one course of ACT rose from 26.2% during July-September 2007 to 72.6% during April-June 2008. The number of malaria patients treated with ACTs gradually increased after the start of the pilot, while the use of non-ACT antimalarials declined; ACTs went from 3% of all antimalarials sold in July 2007 to 26% in June 2008. District-specific data showed substantial variation among the districts in ACT uptake through ADDOs, ranging from ACTs representing 10% of all antimalarial sales

  18. Adjacent central venous catheters can result in immediate aspiration of infused drugs during renal replacement therapy.

    Science.gov (United States)

    Kam, K Y R; Mari, J M; Wigmore, T J

    2012-02-01

    Dual-lumen haemodiafiltration catheters enable continuous renal replacement therapy in the critically ill and are often co-located with central venous catheters used to infuse drugs. The extent to which infusions are immediately aspirated by an adjacent haemodiafiltration catheter remains unknown. A bench model was constructed to evaluate this effect. A central venous catheter and a haemodiafiltration catheter were inserted into a simulated central vein and flow generated using centrifugal pumps within the simulated vein and haemodiafiltration circuit. Ink was used as a visual tracer and creatinine solution as a quantifiable tracer. Tracers were completely aspirated by the haemodiafiltration catheter unless the infusion was at least 1 cm downstream to the arterial port. No tracer was aspirated from catheters infusing at least 2 cm downstream. Orientation of side ports did not affect tracer elimination. Co-location of central venous and haemodiafiltration catheters may lead to complete aspiration of infusions into the haemodiafilter with resultant drug under-dosing. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  19. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.

    Science.gov (United States)

    Yu, Min; Bardia, Aditya; Aceto, Nicola; Bersani, Francesca; Madden, Marissa W; Donaldson, Maria C; Desai, Rushil; Zhu, Huili; Comaills, Valentine; Zheng, Zongli; Wittner, Ben S; Stojanov, Petar; Brachtel, Elena; Sgroi, Dennis; Kapur, Ravi; Shioda, Toshihiro; Ting, David T; Ramaswamy, Sridhar; Getz, Gad; Iafrate, A John; Benes, Cyril; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A

    2014-07-11

    Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease. Copyright © 2014, American Association for the Advancement of Science.

  20. Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death

    Directory of Open Access Journals (Sweden)

    Vlahov David

    2006-01-01

    Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.

  1. Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death

    Directory of Open Access Journals (Sweden)

    David Vlahov

    Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.

  2. Engineered Thermoplasma acidophilum factor F3 mimics human aminopeptidase N (APN) as a target for anticancer drug development.

    Science.gov (United States)

    Su, Jing; Wang, Qiang; Feng, Jinhong; Zhang, Cong; Zhu, Deyu; Wei, Tiandi; Xu, Wenfang; Gu, Lichuan

    2011-05-01

    Human aminopeptidase N (hAPN) is an appealing objective for the development of anti-cancer agents. The absence of mammalian APN experimental structure negatively impinges upon the progression of structure-based drug design. Tricorn interacting factor F3 (factor F3) from Thermoplasma acidophilum shares 33% sequence identity with hAPN. Engineered factor F3 with two point directed mutations resulted in a protein with an active site identical to hAPN. In the present work, the engineered factor F3 has been co-crystallized with compound D24, a potent APN inhibitor introduced by our lab. Such a holo-form experimental structure helpfully insinuates a more bulky pocket than Bestatin-bound Escherichia coli APN. This evidence discloses that compound D24 targetting the structure of E. coli APN cannot bind to the activity cleft of factor F3 with high affinity. Thus, there is a potential risk of inefficiency to design hAPN targeting drug while using E. coli APN as the target model. We do propose here now that engineered factor F3 can be employed as a reasonable alternative of hAPN for drug design and development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Predictors of mortality in patients with extensively drug-resistant Acinetobacter baumannii pneumonia receiving colistin therapy.

    Science.gov (United States)

    Choi, Ik Sung; Lee, Yu Ji; Wi, Yu Mi; Kwan, Byung Soo; Jung, Kae Hwa; Hong, Woong Pyo; Kim, June Myong

    2016-08-01

    The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  4. [Personalized drug therapy-directed clinical pharmacology research based on genetic polymorphisms and pharmacokinetics analysis].

    Science.gov (United States)

    Hayashi, Hideki

    2013-01-01

    In this decade, the field of pharmacogenomics (PGx), which is related to pharmacokinetics (PK) or pharmacodynamics (PD), has attracted much attention because it may provide a possible explanation for individual differences in the clinical efficacy of drugs. For the development of personalized drug therapy, it is important to accumulate evidence from PK/PD/PGx analysis in clinical trials. Warfarin (WF) is one of the most widely prescribed anticoagulants for the prevention and treatment of venous and arterial thromboembolism. However, large interindividual and interethnic differences have been observed in the WF dose required to elicit the anticoagulant effect. We investigated the factors influencing the WF maintenance dose in Japanese patients. Our study confirmed a large interindividual variability in the WF maintenance dose that was due to a VKORC1 1639 G>A polymorphism and differences in body weight, age, and serum albumin. In addition, we found that the CYP4F2 genotype affects the plasma concentration of menaquinone-4, and that this finding was correlated with the WF sensitivity index in Japanese pediatric patients. Methotrexate (MTX) is an antifolate that is widely used to treat rheumatoid arthritis (RA) and cancer. The response to low-dose MTX demonstrated wide interpatient variability; however, the contributing factors remain unclear. We found that the frequency of the RFC1 80A allele was higher in RA patients treated with MTX alone compared with patients who received biological disease-modifying antirheumatic drugs (bDMARDs). This finding may support the combined use of bDMARDs and MTX. Further large-scale prospective clinical trials are required to confirm these findings.

  5. 'Forever Young'-Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises.

    Science.gov (United States)

    Busnelli, Andrea; Somigliana, Edgardo; Vercellini, Paolo

    2017-04-01

    In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as 'late-onset hypogonadism (LOH)'. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Clinical applications of intravenous lipid emulsion therapy.

    Science.gov (United States)

    Muller, Sam H; Diaz, James H; Kaye, Alan David

    2015-12-01

    Intravenous lipid emulsion (ILE; Intralipid) therapy, a standard treatment in local anesthetic toxicity, has demonstrated therapeutic efficacies for a number of different drug class-mediated toxicities. Some of these varied drug groups include antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. To meet the objective of describing the growing number of indications for Intralipid therapy and any diverse effects and/or failures of Intralipid therapy in reversing multiple drug toxicities, we queried several Internet search engines with the key words "intravenous lipid emulsion therapy," "Intralipid," "lipid emulsion," and "local anesthetic systemic toxicity," resulting in the identification of 31 case reports for descriptive analysis. These case reports included 49 separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The education of clinicians regarding the beneficial and varied roles of Intralipid therapy in different clinical settings is warranted, particularly in terms of the potential for Intralipid therapy to reverse the toxicities of non-local anesthetic drugs.

  7. Clinical predictors of aminoglycoside-induced ototoxicity in drug-resistant Tuberculosis patients on intensive therapy.

    Science.gov (United States)

    Sogebi, Olusola Ayodele; Adefuye, Bolanle Olufunlola; Adebola, Stephen Oluwatosin; Oladeji, Susan Modupe; Adedeji, Taiwo Olugbemiga

    2017-08-01

    The study objectives were to determine the incidence of aminoglycoside-induced ototoxicity in institutionalized patients on intensive phase of therapy for drug-resistant Tuberculosis (DR Tb) and also to assess clinical factors which could predict the ototoxicity. The study was a prospective analytical study among consecutive DR Tb patients who were admitted for intensive phase of therapy (of 4 months) at the DR-Tb center over a 12-month period. Patients were diagnosed as DR Tb using the Gene Xpert machine to confirm Rifampicin resistance. All eligible 70 out of 87 consenting patients were consecutively recruited into the study. Patients had baseline (admission) and serial pure tone audiometries (PTAs) performed at 4 weekly intervals until discharge after 4 months of admission. Audiometric confirmation of aminoglycoside-induced ototoxicity was done by comparing serial with baseline PTA. Among the 70 patients the male:female ratio was 1.7:1. Nine patients (12.9%) were retroviral-positive, and 16 patients (22.9%) were confirmed to have ototoxicity by audiometric criteria. The duration of treatment when ototoxicity was detected in the patients ranged 4-17 (Mean±SD; 9.4±3.4) weeks. Ototoxicity was detected in the audiometric low frequency ranges in 7 (43.8%) and at the high frequencies in 4 (25.0%) of the patients. Univariate analyses of clinical parameters found that age, underlying diabetes mellitus, deranged baseline PTAv >25dB HL, BMI on admission and retroviral status were significantly associated, while sex and previous drug regimen failure were not associated with ototoxicity. Multivariate adjusted logistic regression analyses, controlling for sex, revealed age (OR=1.068, p=0.018), BMI on admission (OR=0.673, p=0.012) and retroviral positivity (OR=8.822, p=0.014) of patients could significantly predict aminoglycoside-induced ototoxicity. Incidence of aminoglycoside-induced ototoxicity in DR Tb patients was 22.9%. The clinical predictors for ototoxicity were age

  8. Clinical efficacy of glucocorticoid therapy in treatment of drug-induced cholestatic liver disease

    Directory of Open Access Journals (Sweden)

    GE Hongyan

    2015-10-01

    Full Text Available ObjectiveTo analyze the clinical efficacy of glucocorticoid therapy in addition to conventional treatment for patients with drug-induced cholestatic liver disease. MethodsA total of 115 patients with drug-induced cholestatic liver disease who were admitted to Affiliated Hospital of Inner Mongolia University for the Nationalities from January 2010 to December 2014 were collected and divided into glucocorticoid treatment group and non-glucocorticoid treatment group. The glucocorticoid treatment group was given methylprednisolone sodium succinate 120 mg once daily by intravenous injection in addition to conventional treatment. The indicator for glucocorticoid response was defined as 10% decrease of total bilirubin (TBil on the third day or 30% decrease on the seventh day. Then the patients were orally given prednisone tablets 10 mg three times daily based on the level of TBil, and the administration of prednisone tablets was adjusted to twice daily a week later. The course of treatment was less than three weeks. Comparison of continuous data in normal distribution between the two groups was made by t test, and comparison of continuous data not in normal distribution between the two groups was made by rank sum test. ResultsThe levels of gamma-glutamyl transpeptidase (GGT, alanine aminotransferase (ALT, and TBil in the glucocorticoid treatment group decreased significantly on days 3, 7, and 14 of treatment compared with those before treatment (tGGT=3.64, 13.08, 16.22; tALT=2.39, 4.73, 8.36; tTBil=3.46, 7.41, 13.17; all P<0.05. Compared with the non-glucocorticoid treatment group, the glucocorticoid treatment group had significantly lower AST and ALT levels before treatment and on days 3 and 7 of treatment (all P>0.05. The GGT, AST, and TBil levels in the glucocorticoid treatment group were significantly lower than those in the non-glucocorticoid treatment group on day 14 of treatment (t=7.074, 2.929, 2.018; all P<0.05. The average decreasing

  9. Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals

    Science.gov (United States)

    Thess, Andreas; Grund, Stefanie; Mui, Barbara L; Hope, Michael J; Baumhof, Patrick; Fotin-Mleczek, Mariola; Schlake, Thomas

    2015-01-01

    Being a transient carrier of genetic information, mRNA could be a versatile, flexible, and safe means for protein therapies. While recent findings highlight the enormous therapeutic potential of mRNA, evidence that mRNA-based protein therapies are feasible beyond small animals such as mice is still lacking. Previous studies imply that mRNA therapeutics require chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system. Here we show that chemically unmodified mRNA can achieve those goals as well by applying sequence-engineered molecules. Using erythropoietin (EPO) driven production of red blood cells as the biological model, engineered Epo mRNA elicited meaningful physiological responses from mice to nonhuman primates. Even in pigs of about 20 kg in weight, a single adequate dose of engineered mRNA encapsulated in lipid nanoparticles (LNPs) induced high systemic Epo levels and strong physiological effects. Our results demonstrate that sequence-engineered mRNA has the potential to revolutionize human protein therapies. PMID:26050989

  10. Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.

    Science.gov (United States)

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial communities, whole-cell microorganisms or purified enzymes. In the review these processes are described. Drug design is an iterative process which begins when a chemist identifies a compound that displays an interesting biological profile and ends when both the activity profile and the chemical synthesis of the new chemical entity are optimized. Traditional approaches to drug discovery rely on a stepwise synthesis and screening program for large numbers of compounds to optimize activity profiles. Over the past ten to twenty years, scientists have used computer models of new chemical entities to help define activity profiles, geometries and relativities. This article introduces inter alia the concepts of molecular modelling and contains references for further reading.

  11. Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens.

    Science.gov (United States)

    Vittorino Gaddi, A; Benedetto, D; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

    2014-01-01

    To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and switching therapy. A timespan of 5 years was considered, from 4 years before to 1 year after the index date (i.e. date of the prescription selected in the recruitment period). A medication possession ratio (MPR) with a cut-off value of 80% was used to measure medication adherence. Descriptive statistics and multiple logistic regression were used to define the objectives, while P FDCT, 1 (IQR 0.29, 68,5% compliant); and LDCT, 0.89 (IQR 0.33, 60.3% compliant). FDCT and LDCT were significantly correlated with MPR. Compliance was 48.9% in the prevalent patient cohort (i.e. patients prescribed oral antidiabetic therapy in both prerecruitment and recruitment periods); median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.52); FDCT, 1 (IQR 0.28); and LDCT, 0.90 (IQR 0.32). Compliance was 43.0% in the incident patient cohort (i.e. patients who were first prescribed oral antidiabetic therapy in the recruitment period); median MPRs for the treatment regimens were: MT, 0.70 (IQR, 0.58); FDCT, 1 (IQR 0

  12. Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia.

    Science.gov (United States)

    Parchem, N L; Bauer, K A; Cook, C H; Mangino, J E; Jones, C D; Porter, K; Murphy, C V

    2016-09-01

    Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy</