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Sample records for antiarrhythmic drug therapy

  1. Optimal antiarrhythmic drug therapy for electrical storm

    OpenAIRE

    Sorajja, Dan; Munger, Thomas M.; Shen, Win-Kuang

    2015-01-01

    Abstract Electrical storm, defined as 3 or more separate episodes of ventricular tachycardia or ventricular fibrillation within 24 hours, carries significant morbidity and mortality. These unstable ventricular arrhythmias have been described with a variety of conditions including ischemic heart disease, structural heart disease, and genetic conditions. While implantable cardioverter defibrillator implantation and ablation may be indicated and required, antiarrhythmic medication remains an imp...

  2. [Non-antiarrhythmic drug therapy for the prevention of atrial fibrillation?].

    Science.gov (United States)

    Fauchier, L; Zannad, N; Clementy, N; Pierre, B; Cosnay, P; Babuty, D

    2010-12-01

    In atrial fibrillation (AF), the absence of a clear benefit of a rhythm-control strategy over a rate-control strategy seen in recent trials may be due to the fact that many of the usual antiarrhythmic strategy have significant weaknesses. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed 'upstream'of the electrical aspects of AF, towards the underlying anatomical substrate and atrial remodelling, have been proposed as new pharmacological therapeutic approaches. Potential upstream therapies for AF comprise a variety of agents such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), statins, N-3 polyunsaturated fatty acids and steroids. On the basis of experimental data, clinical studies have provided information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In patients with heart failure or hypertension, data are sufficient to support the use of ACEI or ARB as treatment that may decrease the risk of AF beyond their other beneficial effects. Similarly, it is highly possible that the use of statin in patients with a recognized indication may be associated with a benefit against AF. However, in most clinical settings, the evidence appears to be insufficient to drive changes in therapy management per se, and large-scale, randomized controlled trials with adequately defined endpoints are still needed. The results from these trials may help to understand the complex mechanisms that lead to AF, and may clarify the benefit-to-risk ratio of these new therapeutic approaches. PMID:21211623

  3. Use of antiarrhythmic drugs in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Hon-Chi Lee; Kristin TL Huang; Win-Kuang Shen

    2011-01-01

    Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability.Cardiac arrhythmias,including atrial fibrillation,sudden cardiac death,and bradycardia requiring pacemaker placement,all increase exponentially after the age of 60.It is important to distinguish between the normal,physiological consequences of aging on cardiacelectrophysiology and the abnormal,pathological alterations.The age-related cardiac changes include ventricular hypertrophy,senileamyloidosis,cardiac valvular degenerative changes and annular calcification,fibrous infiltration of the conduction system,and loss of naturalpacemaker cells and these changes could have a profound effect on the development of arrhythmias.The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intracellular Ca2+ overload which promote the development of cardiac an-hythmias.As ion channels are the substrates of antiarrhythmic drugs,it follows that the pharmacoldnetics and pharmacodynamics of these drugs will also change with age.Aging alters the absorption,distribution,metabolism,and elimination of antiarrhythmic drugs,so liver and kidney function must be monitored to avoid potential adverse drug effects,and antiarrhythmic dosing may need to be adjusted for age.Elderly patients are also more susceptible to the side effects of many antiarrhythmics,including bradycardia,orthostatic hypotension,urinary retention,and falls.Moreover,the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polyphanmacy,and the astute physician must pay careful attention to potential drug-drug interactions.Finally,it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology,disease processes,and medication regimen.

  4. Targeting ryanodine receptors for anti-arrhythmic therapy

    Institute of Scientific and Technical Information of China (English)

    Mark D McCAULEY; Xander H T WEHRENS

    2011-01-01

    Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca2+) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca2+ release has been linked to arrhythmogenesis in both the inherited arrhythmia synSeveral classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca2+ leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.

  5. Consequences of antiarrhythmic drugs on cardiac energetics

    Czech Academy of Sciences Publication Activity Database

    Převorovská, Světlana; Maršík, František

    Plzeň : Západočeská univerita, 2007, s. 1-2. ISBN 978-80-7043-607-3. [IMACS 2007. Plzeň (CZ), 10.09.2007-13.09.2007] R&D Projects: GA ČR(CZ) GA106/03/0958; GA ČR GA106/03/1073 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac energetics * antiarrhythmic drugs * numerical simulation Subject RIV: BK - Fluid Dynamics

  6. The implantable defibrillator and antiarrhythmic drugs--competitive and complementary treatment for severe ventricular arrhythmia.

    Science.gov (United States)

    Dorian, P; Newman, D

    1993-11-01

    Most patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) are at high risk of recurrence. Implanted defibrillators (ICDs) are highly effective in sensing and converting VT or VF to a perfusing rhythm. "Conventional" antiarrhythmic agents, which primarily block cardiac sodium channels, are relatively ineffective in preventing arrhythmia recurrence; amiodarone and sotalol appear to be effective in reducing recurrence and mortality rates, although the extent of benefit is not well understood. Despite the apparent advantage of ICDs, they have short- and long-term complications, are costly, and their benefit in prolonging the quantity or quality of life remains unproven. Randomized clinical trials which compare the effect of ICDs with that of antiarrhythmic drugs on mortality, cost, and quality of life will be necessary to understand how patients with malignant arrhythmias ought to be treated. If an ICD is implanted, adjunctive therapies need to be considered to treat the underlying heart disease and to derive optimum benefit from the device. Drugs may have beneficial or adverse interactions with devices, and the full understanding of these interactions requires further study. PMID:8269662

  7. Idiopathic ventricular tachycardia: transcatheter ablation or antiarrhythmic drugs?

    Directory of Open Access Journals (Sweden)

    Claudio Tondo; Corrado Carbucicchio; Antonio Dello Russo; Benedetta Majocchi; Martina Zucchetti; Francesca Pizzamiglio; Fabrizio Bologna; Fabio Cattaneo; Daniele Colombo; Eleonora Russo; Michela Casella

    2015-02-01

    Full Text Available Introduction Ventricular tachycardia or frequent premature ventricular contractions (PVCs can occur in the absence of any detectable structural heart disease. In this clinical setting, these arrhythmias are termed idiopathic. Usually, they carry a benign prognosis and any potential ablative intervention is carried out if patients are highly symptomatic or, more importantly, if frequent ventricular arrhythmias can lead to ventricular dysfunction. Methods In this paper, different forms of idiopathic ventricular tachycardia are reviewed. Outflow tract ventricular tachycardia from the right ventricle is the most frequent form of the so-called idiopathic ventricular tachycardia. Other forms of idiopathic ventricular arrhythmias include ventricular tachycardia/PVCs arising from tricuspid annulus, from the mitral annulus, inter-fascicular ventricular tachycardia and papillary muscle ventricular tachycardia. When interventional treatment is deemed necessary, detailed mapping ( earliest activation during VT/PVC, pace mapping is crucial as to identify the successful ablation site. Catheter ablation more than antiarrhythmic drug treatment is usually highly effective in eliminating idiopathic ventricular arrhythmias and providing prevention of recurrence. Conclusion Idiopathic VTs are not considered life-threatening arrhythmias and, prevention of recurrences is often achieved by means of catheter ablation that provides an improvement of quality of life. The overall acute success rate of catheter ablation is about 85-90% with a long–term prevention of arrhythmia recurrence of about 75-80%. It is advisable that the procedure is carried out by electrophysiologists with expertise in VT catheter ablation and extensive knowledge of cardiac anatomy as to ensure a high success rate and reduce the likelihood of major complications.

  8. A general mechanism for drug promiscuity: Studies with amiodarone and other antiarrhythmics.

    Science.gov (United States)

    Rusinova, Radda; Koeppe, Roger E; Andersen, Olaf S

    2015-12-01

    Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels' sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics--amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific--perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane-like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents. PMID:26573624

  9. Interactions between antiarrhythmic drugs and food Interacciones entre fármacos antiarrítmicos y alimentos

    OpenAIRE

    B. Jáuregui-Garrido; Jáuregui-Lobera, I

    2012-01-01

    Objective: A drug interaction is defined as any alteration, pharmacokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. These interactions can affect the antiarrhythmic drugs, altering their therapeutic efficacy and adverse effects. The aim of this study was to conduct a review of available data about interactions between antiarrhythmic drugs and food. Methods: The purpose of this review was to rep...

  10. ST segment elevation in the right precordial leads following administration of class Ic antiarrhythmic drugs

    OpenAIRE

    Yasuda, M.; Nakazato, Y.; Yamashita, H.; Sekita, G; Kawano, Y.; Mineda, Y; Nakazato, K.; Tokano, T; Sumiyoshi, M; Nakata, Y.

    2001-01-01

    Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and...

  11. Lung injury by amiodarone, an antiarrhythmic drug, in male rats.

    Science.gov (United States)

    Padmavathy, B; Niranjali, S; Devaraj, H

    1992-07-01

    Administration of single dose (175 mg/kg body wt) of amiodarone dissolved in water through gavage for 3 weeks damaged the lung and changed the content of lung lavage. Activities of bronchoalveolar lavage (BAL) angiotensin converting enzyme (ACE) and lactate dehydrogenase (LDH) increased significantly. Also, the protein and lactate content of the lavage fluid increased significantly over the control. The drug also produced marked changes in morphology of the lung of experimental animals. PMID:1459640

  12. Numerical simulation of antiarrhythmic drugs effects on cardiac action potential

    Czech Academy of Sciences Publication Activity Database

    Převorovská, Světlana; Maršík, František

    Brno : Brno University of Technology, 2006 - (Burša, J.; Fuis, V.), s. 170-171 ISBN 80-214-3232-2. [ Human Biomechanics 2006. Hrotovice (CZ), 13.11.2006-16.11.2006] R&D Projects: GA ČR(CZ) GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : human cardiovascular system * cardiac action potential * antiarrhytmmic drugs-cell channel interaction Subject RIV: BK - Fluid Dynamics

  13. THE POSSIBILITIES OF ANTIARRHYTHMIC THERAPY IN PRIMARY PREVENTION OF DEATH IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS

    Directory of Open Access Journals (Sweden)

    Yu. A. Bunin

    2016-01-01

    Full Text Available Highlights of primary prevention of death in patients with ventricular arrhythmias (VA are discussed. Overview of all main clinical trials exploring various anti-arrhythmic drugs in prevention of death in patients with VA is presented. It is emphasized that in patients with organic heart disease and VA only beta-blockers and amiodarone are able to reduce mortality, while other drugs have no effect on mortality, or they even increase mortality mainly due to arrhythmogenic effect. Recent clinical studies of the cardioverter-defibrillators efficacy in these patients are presented. It is shown that the use of cardioverter defibrillators compared with pharmacotherapy is more effective in prevention of fatal outcomes.

  14. Voltage and frequency dependent block of sodium current in cardiac cells. Comparison of the effect of two antiarrhythmic drugs

    Czech Academy of Sciences Publication Activity Database

    Matějovič, P.; Bahníková, M.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    Brno : Brno University of Technology, 2002 - (Jan, J.; Kozumplík, J.; Provazník, I.), s. 214-216 ISBN 80-214-2633-0. ISSN 1211-412X. [Biosignal 2002. Brno (CZ), 26.06.2002-28.06.2002] Institutional research plan: CEZ:AV0Z2076919 Keywords : cardiac cell * sodium current * antiarrhythmic drugs Subject RIV: BO - Biophysics

  15. A benefit-risk assessment of class III antiarrhythmic agents

    DEFF Research Database (Denmark)

    Elming, Hanne; Brendorp, Bente; Pehrson, Steen;

    2004-01-01

    relief. Since many patients experience a decrease in physical performance as well as a diminished quality of life during arrhythmia there is still a need for antiarrhythmic drug therapy. The development of new antiarrhythmic agents has changed the focus from class I to class III agents since it became...... evident that with class I drug therapy the prevalence of mortality is considerably higher. This review focuses on the benefits and risks of known and newer class III antiarrhythmic agents. The benefits discussed include the ability to maintain sinus rhythm in persistent atrial fibrillation patients, and...... reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia....

  16. A benefit-risk assessment of class III antiarrhythmic agents

    DEFF Research Database (Denmark)

    Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian;

    2002-01-01

    With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural hear...

  17. Interactions between antiarrhythmic drugs and food Interacciones entre fármacos antiarrítmicos y alimentos

    Directory of Open Access Journals (Sweden)

    B. Jáuregui-Garrido

    2012-10-01

    Full Text Available Objective: A drug interaction is defined as any alteration, pharmacokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. These interactions can affect the antiarrhythmic drugs, altering their therapeutic efficacy and adverse effects. The aim of this study was to conduct a review of available data about interactions between antiarrhythmic drugs and food. Methods: The purpose of this review was to report an update of the existing literature data on the main findings with respect to food and antiarrhythmic drugs interactions by means of a search conducted in PubMed, which yielded a total of 250 articles initially. Results: After excluding different articles which were not focusing on the specific objective, the main results refer to interactions among antiarrhythmic drugs and food in general, grapefruit juice, and others like fibre or medicinal plants. Discussion: Food may affect the bioavailability of antiarrhythmic drugs and in some specific cases (dairy products, rich-in-protein diets, grapefruit juice, this should be carefully considered. The best recommendation seems to advise patients to remove the grapefruit juice from their diet when treatment with these drugs. Fibre should be separated from taking these drugs and regarding medicinal plants and given their increased use, the anamnesis must include information about its use, the reason for that use and what types of plants are used, all in order to give the corresponding recommendations.Objetivo: La interacción de medicamentos se define como cualquier alteración, farmacocinética y/o farmacodinámica, producida por diferentes sustancias, otros tratamientos, factores dietéticos y hábitos como beber y fumar. Estas interacciones pueden afectar a los fármacos antiarrítmicos, alterando su eficacia terapéutica y sus efectos adversos. El objetivo de este estudio fue realizar una revisión de los

  18. Radiofrequency catheter ablation maintains its efficacy better than antiarrhythmic medication in patients with paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Raatikainen, M J Pekka; Hakalahti, Antti; Uusimaa, Paavo; Nielsen, Jens Cosedis; Johannessen, Arne; Hindricks, Gerhard; Walfridsson, Håkan; Pehrson, Steen; Englund, Anders; Hartikainen, Juha; Kongstad, Ole; Mortensen, Leif Spange; Hansen, Peter Steen

    2015-01-01

    BACKGROUND: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order...... events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P=0.10). CONCLUSIONS: In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic...

  19. PROPAFENONE, A NEW EFFECTIVE ANTIARRHYTHMIC DRUG. REPORT OF 2 YEARS CLINICAL EXPERIMENT WITH PROPAFENONE (WITH BRIEF REVIEW OF ARTICLES)

    OpenAIRE

    IRAJ NAZERY; ARCHIMEDES SANATY

    1986-01-01

    Propafenone HCI (p), is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p) in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics) . Intravenously adminis...

  20. Cost Effectiveness of Implantable Cardioverter Defibrillator Therapy versus Drug Therapy for Patients at High Risk of Sudden Cardiac Death

    OpenAIRE

    Spath, Marian A.; Bernie J. O'Brien

    2002-01-01

    The implantable cardioverter defibrillator (ICD) is a therapy for patients at risk of sudden cardiac death due to ventricular tachycardia (VT) or ventricular fibrillation (VF). But the apparent high cost of ICD therapy relative to antiarrhythmic drugs such as amiodarone has raised questions about the cost effectiveness of ICD therapy versus drug therapy. To inform this debate we reviewed the literature on ICD cost effectiveness. An electronic and manual search was conducted for articles publi...

  1. Acupuncture Antiarrhythmic Effects on Drug Refractory Persistent Atrial Fibrillation: Study Protocol for a Randomized, Controlled Trial

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    Jimin Park

    2015-01-01

    Full Text Available Background. Atrial fibrillation (AF is the most common form of arrhythmia. Several trials have suggested that acupuncture may prevent AF. However, the efficacy of acupuncture for AF prevention has not been well investigated. Therefore, we designed a prospective, two-parallel-armed, participant and assessor blinded, randomized, sham-controlled clinical trial to investigate acupuncture in persistent AF (ACU-AF. Methods. A total of 80 participants will be randomly assigned to active acupuncture or sham acupuncture groups in a 1 : 1 ratio. Both groups will take the same antiarrhythmic medication during the study period. Patients will receive 10 sessions of acupuncture treatment once a week for 10 weeks. The primary endpoint is AF recurrence rate. Secondary endpoints are left atrium (LA and left atrial appendage (LAA changes in function and volume, and inflammatory biomarker changes. Ethics. This study protocol was approved by the institutional review boards (IRBs of Kyung Hee University Hospital (number 1335-04. This trial is registered with clinicaltrials.gov NCT02110537.

  2. Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

    DEFF Research Database (Denmark)

    Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

    2015-01-01

    Torsades de Pointes (TdP) is a potentially lethal cardiac arrhythmia and a known adverse effect of many drugs secondary to block of the rapidly activating delayed rectifier potassium current (IKr). In animal models antipsychotic drugs have shown reduced pro-arrhythmic potential compared to drugs...

  3. Class IC antiarrhythmic drug induced atrial flutter: electrocardiographic and electrophysiological findings and their importance for long term outcome after right atrial isthmus ablation

    OpenAIRE

    Nabar, A; Rodriguez, L.; Timmermans, C; van Mechelen, R; Wellens, H

    2001-01-01

    OBJECTIVE—To describe the electrocardiographic and electrophysiological findings of new atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation, and to report the long term results of right atrial isthmus ablation in relation to the ECG pattern of spontaneous atrial flutter.
DESIGN—Retrospective analysis.
SETTING—Tertiary care academic hospital.
PATIENTS—24 consecutive patients with atrial fibrillation (age 54 (12) years; 5 female, 19 male)...

  4. PROPAFENONE, A NEW EFFECTIVE ANTIARRHYTHMIC DRUG. REPORT OF 2 YEARS CLINICAL EXPERIMENT WITH PROPAFENONE (WITH BRIEF REVIEW OF ARTICLES

    Directory of Open Access Journals (Sweden)

    IRAJ NAZERY

    1986-05-01

    Full Text Available Propafenone HCI (p, is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics . Intravenously administered, (P was effective in 85% of patients with paroxysmal reentrant supraventricular tachycardia (PRSVT, 75% of those with paroxysmal atrial fibrillation (PAF , 50% and 42% of those with refractory premature ventricular contractions (PVC and ventricular tachycardia (V. Tach, respectively. Orally administered, (P was effective in 73% of those with resistant PVCs and nonsustained ventricular tachycardia (NSV Tach, and 75% of those with resistant sustained ventricular tachycardia (RSVT •

  5. Adenylyl Cyclase Signaling in the Developing Chick Heart: The Deranging Effect of Antiarrhythmic Drugs

    Directory of Open Access Journals (Sweden)

    Lucie Hejnova

    2014-01-01

    Full Text Available The adenylyl cyclase (AC signaling system plays a crucial role in the regulation of cardiac contractility. Here we analyzed the key components of myocardial AC signaling in the developing chick embryo and assessed the impact of selected β-blocking agents on this system. Application of metoprolol and carvedilol, two commonly used β-blockers, at embryonic day (ED 8 significantly downregulated (by about 40% expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gsα protein at ED9. Activity of AC stimulated by forskolin was also significantly reduced under these conditions. Interestingly, when administered at ED4, these drugs did not produce such profound changes in the myocardial AC signaling system, except for markedly increased expression of Giα protein. These data indicate that β-blocking agents can strongly derange AC signaling during the first half of embryonic heart development.

  6. Anti-arrhythmic Medication Propafenone a Potential Drug for Alzheimer's Disease Inhibiting Aggregation of Aβ: In Silico and in Vitro Studies.

    Science.gov (United States)

    Ngo, Son Tung; Fang, Shang-Ting; Huang, Shu-Hsiang; Chou, Chao-Liang; Huy, Pham Dinh Quoc; Li, Mai Suan; Chen, Yi-Cheng

    2016-07-25

    Alzheimer's disease (AD) is the most common form of dementia caused by the formation of Aβ aggregates. So far, no effective medicine for the treatment of AD is available. Many efforts have been made to find effective medicine to cope with AD. Curcumin is a drug candidate for AD, being a potent anti-amyloidogenic compound, but the results of clinical trials for it were either negative or inclusive. In the present study, we took advantages from accumulated knowledge about curcumin and have screened out four compounds that have chemical and structural similarity with curcumin more than 80% from all FDA-approved oral drugs. Using all-atom molecular dynamics simulation and the free energy perturbation method we showed that among predicted compounds anti-arrhythmic medication propafenone shows the best anti-amyloidogenic activity. The in vitro experiment further revealed that it can inhibit Aβ aggregation and protect cells against Aβ induced cytotoxicity to almost the same extent as curcumin. Our results suggest that propafenone may be a potent drug for the treatment of Alzheimer's disease. PMID:27304669

  7. Drug therapies in dermatology.

    Science.gov (United States)

    Aslam, Arif; Griffiths, Christopher E M

    2014-02-01

    This article explores the current and emerging therapies for skin disease, with a particular focus on chronic plaque psoriasis and metastatic malignant melanoma. We discuss the current biological therapies used for psoriasis and those on the horizon, including small molecules and biosimilars. We also summarise the recent advances in the use of novel therapeutic agents in other dermatological diseases and outline the promise of translational research and stratified medicine approaches in dermatology. Better matching of patients with therapies is anticipated to have a major effect on both clinical practice and the development of new drugs and diagnostics. PMID:24532745

  8. [Drug therapy for cough].

    Science.gov (United States)

    Koskela, Heikki; Naaranlahti, Toivo

    2016-01-01

    An efficient therapy for cough usually requires identification and treatment of the underlying disease, like asthma. However an underlying disease in cough is not found in all cases and conventional treatment of the underlying disease is ineffective against cough. Drug therapy options are available also for these situations. Honey or menthol can be tried for cough associated with respitatory infections, antihistamines for cough associated with allergic rhinitis, blockers of the leukotriene receptor or muscarinic receptor for asthma-associated cough and morphine for cough associated with a malignant disease. Menthol, blockers of the muscarinic receptor, or dextrometorphan can be tried for prolonged idiopathic cough. Codeine is not necessary in the treatment of cough. Refraining from drug treatment should always be considered. PMID:27089619

  9. Treatment strategy of antiarrhythmic drugs in atrial fibrillation%房颤抗心律失常药物治疗策略的选择

    Institute of Scientific and Technical Information of China (English)

    郑刚

    2012-01-01

    The prevalence of atrial fibrillation (AF) is extensively increased. AF can cause a number of clinical serious outcomes, including stroke, life quantity and movable ability descent, hospitalization rate increment, left ventricular dysfunction and death. Based on updated clinical evidence, this review presents a solution for the treatment strategy of antiarrhythmic drugs in AF patients.%房颤(AF)病例分布广,发病率增长快,相关临床后果严重,如脑卒中、生活质量及活动能力下降、住院率增加、左室功能下降乃至死亡等.对AF患者的抗心律失常药物治疗,必须面对两种治疗策略的选择.本文综合近期陆续发表的一些临床研究结果,初步探讨临床治疗策略选择.

  10. Intoxicaciones medicamentosas (I: Psicofármacos y antiarrítmicos Acute pharmacologic poisoning (I: Psychotropic and antiarrhythmic drugs

    Directory of Open Access Journals (Sweden)

    I. Osés

    2003-01-01

    Full Text Available En la valoración de la Intoxicación Medicamentosa Aguda (IMA en pacientes graves con dosis potencialmente no tóxicas del teórico fármaco responsable es importante insistir en la anamnesis en la coingesta de otros fármacos o tóxicos. Inicialmente se prestará atención a las medidas de soporte vital, oxigenando, protegiendo la vía aérea y expandiendo la volemia. El ECG es una herramienta diagnóstica de primer orden en las IMA, sobre todo por antidepresivos tricíclicos (ADT y medicación cardiovascular. Su monitorización continua durante las primeras 12-24 horas suele ser necesaria en la mayoría de los casos. Las benzodiacepinas no suelen producir intoxicaciones graves. El uso del flumazenilo se reservará a los casos de depresión respiratoria, coma profundo o de causa no filiada. Pueden dar lugar a convulsiones, sobre todo en caso de intoxicación mixta con antidepresivos, y síndrome de abstinencia. Los ADT poseen una potencial gravedad enorme, pudiendo originar arritmias mortales. El rango terapéutico del litio es muy estrecho, pudiendo producirse signos de toxicidad fundamentalmente digestiva y neurológica. En caso de intoxicación por digoxina, se considerará el uso de anticuerpos antidigital en caso de bradiarritmias graves, bloqueos AV o PCR. El glucagón es el antídoto para la intoxicación grave por ß-bloqueantes y para la hipotensión refractaria en caso de calcioantagonistas.In the evaluation of Acute Drug Poisoning (ADP in patients seriously ill with a potentially non-toxic dose of the drug that is theoretically responsible, it is important to insist on anamnesis in the coingestion of other drugs or toxics. Initially attention is given to life support measures, oxygenation, protection of the airway and expanding the volemia. The ECG is a diagnostic tool of the first order in ADPs, above all for tricyclic antidepressants (TAD and cardio-vascular drugs. In the majority of cases continuous monitoring is usually

  11. [Drug therapy of arthrosis].

    Science.gov (United States)

    Steinmeyer, J

    2001-11-01

    Osteoarthritis is one of the most common and economically important chronic diseases amongst adults, especially those of a senior age. There now exists a range of effective medications, which either alone or in combination can alleviate the symptoms of the disease and improve the quality of life. Because these medications are not always sufficiently effective and must sometimes be interrupted due to side effects, a large arsenal of active agents is necessary. Alleviation of pain and inhibition of inflammation are the primary goals of pharmacotherapy, whereby the objective is to return an active or transiently painful, decompensated osteoarthritis to a latent (silent, pain-free) condition. This therapeutic goal can almost always be accomplished by using analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), or intraarticular injection of glucocorticoids. The main problem in administering NSAIDs is their gastrointestinal toxicity,for which a prophylactic medication (e.g., simultaneous application of misoprostol or switching to a COX-2 selective NSAID) should be considered especially with risk groups. The newly developed COX-2 selective NSAIDs represent a true enrichment of our therapeutic options. The spectrum of indications for COX-2 selective NSAIDs should in the future correspond to that of older NSAID preparations, providing that no as yet unknown and serious side effects come to light from their use. Pharmacological results published until now confirm that a clinically relevant analgesic and/or anti-inflammatory effect is associated with the use of SYSA-DOAs (symptomatic slow acting drugs in osteoarthritis). However, no clinical studies exist which can positively confirm prevention of morphologically recognizable cartilage defects in man, or a slowing down or reversal of any progressively developing joint cartilage destruction by any individual medication. Neither the benefits, risks, pharmaceutical quality, nor composition of Orthokin are known, and for

  12. [Drug therapy in interventional radiology].

    Science.gov (United States)

    Sumkauskaite, M; Bryant, M; Kortes, N; Stampfl, U; Radeleff, B

    2015-06-01

    In the context of pre-interventional drug therapy, a premedication is given to patients who are known to have an allergy to contrast media, have renal impairment or hyperthyroidism. An already existing anticoagulation therapy, in anticipation of the planned intervention, must be reviewed and changed or even suspended as required. For peri-interventional drug therapy it is important to consider how strenuous the procedure will be as well as the general condition of the patient. Further discussion with anesthetists may be required for the planning of pain therapy or sedation during the procedure. These factors help to ensure maximum patient comfort as well as the success of the intervention. Post-interventional anticoagulation therapy, usually started peri-interventionally, plays an important role in minimizing the risk of acute thrombosis as well as in maintaining long-term functioning of the implanted material. The form of the anticoagulation therapy is set according to the type of intervention. PMID:26063076

  13. Drug Therapy in Diarrhea

    OpenAIRE

    Khalili, M

    1985-01-01

    The drug used in diarrhea must be effective in that they reduce the secretion and increase the absorption of the intestinal mucosa. This seems to be only possible with morphine derivatives. But these are not recommended as they may cause ileus. Antibiotics are indicated in only few cases of severe intestinal infections. Other frequently used drugs such as adsorbents are practically of no effect. Thus, rehydration, electrolyte substitution and realimentation remain the most effective method of...

  14. Drug Therapy in Diarrhea

    Directory of Open Access Journals (Sweden)

    M Khalili

    1985-09-01

    Full Text Available The drug used in diarrhea must be effective in that they reduce the secretion and increase the absorption of the intestinal mucosa. This seems to be only possible with morphine derivatives. But these are not recommended as they may cause ileus. Antibiotics are indicated in only few cases of severe intestinal infections. Other frequently used drugs such as adsorbents are practically of no effect. Thus, rehydration, electrolyte substitution and realimentation remain the most effective method of treatment of acute diarrhea in infants.

  15. Monitoring drug therapy.

    Science.gov (United States)

    Buclin, Thierry; Gotta, Verena; Fuchs, Aline; Widmer, Nicolas; Aronson, Jeffrey

    2012-06-01

    Drug development has improved over recent decades, with refinements in analytical techniques, population pharmacokinetic-pharmacodynamic (PK-PD) modelling and simulation, and new biomarkers of efficacy and tolerability. Yet this progress has not yielded improvements in individualization of treatment and monitoring, owing to various obstacles: monitoring is complex and demanding, many monitoring procedures have been instituted without critical assessment of the underlying evidence and rationale, controlled clinical trials are sparse, monitoring procedures are poorly validated and both drug manufacturers and regulatory authorities take insufficient account of the importance of monitoring. Drug concentration and effect data should be increasingly collected, analyzed, aggregated and disseminated in forms suitable for prescribers, along with efficient monitoring tools and evidence-based recommendations regarding their best use. PK-PD observations should be collected for both novel and established critical drugs and applied to observational data, in order to establish whether monitoring would be suitable. Methods for aggregating PK-PD data in systematic reviews should be devised. Observational and intervention studies to evaluate monitoring procedures are needed. Miniaturized monitoring tests for delivery at the point of care should be developed and harnessed to closed-loop regulated drug delivery systems. Intelligent devices would enable unprecedented precision in the application of critical treatments, i.e. those with life-saving efficacy, narrow therapeutic margins and high interpatient variability. Pharmaceutical companies, regulatory agencies and academic clinical pharmacologists share the responsibility of leading such developments, in order to ensure that patients obtain the greatest benefit and suffer the least harm from their medicines. PMID:22360377

  16. 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

  17. Alternative Drugs in Pain Therapy

    OpenAIRE

    İlker Kelle

    2006-01-01

    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, ...

  18. Theophylline and Antiarrhythmics

    Science.gov (United States)

    Vandemark, F. L.

    Liquid chromatography has become a major analytical technique in the laboratory concerned with therapeutic drug monitoring. This acceptance arises from a number of important factors, including the unusual versatility of the technique, its potential use in the routine determination of drug substances, and the nondestructive nature of the detection systems commonly used.

  19. [Hemophilia B replacement therapy drugs].

    Science.gov (United States)

    Yan, Hong; Zeng, Fanyi

    2016-02-01

    Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs. PMID:27382766

  20. Determination of the novel antiarrhythmic drug sulcardine sulfate in human plasma by liquid chromatography tandem mass spectrometry and its application in a clinical pharmacokinetic study.

    Science.gov (United States)

    Jia, Jingying; Liu, Gangyi; Zhang, Mengqi; Lu, Youli; Lu, Chuan; Liu, Yun; Zheng, Hongcao; Wang, Wei; Gui, Yuzhou; Yu, Chen; Li, Shuijun; Wang, Yiping

    2016-08-01

    Sulcardine sulfate (Sul), a novel antiarrhythmic agent, is currently in phase I and phase II clinical trials. To elucidate its clinical pharmacokinetic characteristics, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of Sul in human plasma. Plasma samples were precipitated by acetonitrile and isotope-labeled sulcardine was added as internal standard. The analysis was carried out on a Capcell Pak C18 MG III column (100 × 2.0 mm, 5 μm) with 0.1% formic acid in acetonitrile solution and water (17:83, v/v) as mobile phase. The linear range was 5.0-1000 ng/mL for Sul, with a lower limit of quantification of 5.0 ng/mL. The intra- and inter-batch CVs were within ±11.0% and the accuracies were 4.9-107.3%. Our method, for the first time, allows the rapid (only 3.0 min) and accurate quantification of Sul in human plasma. The method has been successfully applied in the pharmacokinetic study of Sul in a clinical trial following oral administration of Sul to healthy volunteers. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26715470

  1. Public understanding of drug therapy.

    Science.gov (United States)

    Herxheimer, Andrew

    2012-06-01

    Knowing some basic principles about medicines would help patients to understand drug therapy and to help and encourage them to use it well. These principles relate to the categories and names of drugs, their different uses, how they reach the site of action (absorption, distribution, fate), how they produce their effects, both beneficial and harmful, the time courses of drug actions, how the pattern and intensity of the effects of a drug depend on dose and timing, drug interactions, how drug effects are demonstrated and investigated and sources of information and their trustworthiness. These basic principles are an essential part of health literacy and understanding them would enable individuals to comprehend better the information that they are likely to receive about medicines that they will take. Different populations need different types of education. For schoolchildren, the principles could fit into biology and domestic science teaching, starting in the later years of primary school or early in secondary school. A teaching package would also be needed for their teachers. For adults, web-based learning seems the most practical option. Web-based programmes could be supported by the NHS and professional bodies and through public libraries and local community health services. Specific groups for targeting could include young mothers and carers of chronically ill people. For retired people, one could envisage special programmes, perhaps in collaboration with the University of the Third Age. Conversations between patients and professionals would then become more effective and help shared decision making. PMID:22360596

  2. ANTIARRHYTHMIC EFFICACY OF PROPAFENONE IN PATIENTS WITH PERSISTENT ATRIAL FIBRILLATION

    Directory of Open Access Journals (Sweden)

    R. D. Kurbanov

    2016-01-01

    Full Text Available Aim. To assess propafenone antiarrhythmic efficacy and optimal timing of the drug administration for relief of persistent atrial fibrillation (PAF. Material and methods. 24 patients (19 men, 5 women, aged 53,8±13,3 with PAF (duration is more than 7 days were included in the study. PAF was confirmed clinically as well as by ECG and daily ECG monitoring. Indications for sinus rhythm recovery by propafenone were defined in according to the ACC/AHA/ESC recommendations (2006. 12-lead ECG was performed before the fist administration and 2, 4, 8, 12, 24 hours and some next days after propafenone therapy start. Echocardiography and thyroid hormone tests were also performed. Propafenone was administered additionally to standard treatment of the underlying disease and oral anticoagulants. The first dose of propafenone was 300 mg, after 4 hours patients received next dose of 300 mg if atrial fibrillation persisted and no side effects were observed, then doses of 300 mg were administered every 6-8 hours (but not more than 900-1200 mg per day during 5 days. Maintenance propafenone dose of 450-600 mg daily was used in case of sinus rhythm recovery. Results. Sinus rhythm was restored in 41,6% of patients taking propafenone, and time of sinus rhythm recovery was 53,1±28,9 hours after therapy start. Propafenone antiarrhythmic efficacy in the loading dose (300 mg was 4,2%. Propafenone efficacy during the first 24 hours (dose of 700±282,8 mg was 12,5%. The maximum rate of sinus rhythm recovery was observed during the first 2-3 days of propafenone receiving (60% of all patients with rhythm recovery. Patients with unrecovered sinus rhythm had longer duration of PAF in comparison with this in effectively treated patients, 105,8±89,0 vs 39,7±38,9 days (p<0,05, respectively, as well as the more prominent basal pulse deficit, 24,6±15,0 vs 13,56±5,7 beats per minute (p<0,05, respectively. Cardiac and transient noncardiac side effects were registered in 8,6 and 4

  3. Emerging drug therapies for frailty.

    Science.gov (United States)

    Jeffery, Christopher A; Shum, David W C; Hubbard, Ruth E

    2013-01-01

    The metaphor of a frail older person as a car running out of petrol seems to have resonance in the lay media. Though it may be an over simplistic representation of a complex and dynamic process, it does facilitate discussion with patients and their relatives about the appropriateness of interventions, such as whether or not there is enough fuel (physiological reserves) to get up a really steep hill (undergo a coronary bypass graft). It can also be used as a way to emphasise what can be done to help. For example, in some longitudinal studies, 5% of older patients are less frail after 5 years follow up, suggesting there are things that can still be done to "fill up the tank". This review will consider whether drug therapies can fulfil this role. Frail older people are often prescribed long lists of medications but it is debatable whether current treatments actually address the causes or consequences of frailty itself. Here, we explore the associations between frailty and co-morbidity and evaluate whether the management of chronic disease may impact frailty development or progression. We consider how the management of hypertension may have an important role in the prevention of frailty, mediated by reduction of cerebrovascular disease, but why aggressive management of hypertension may have negative consequences for those who are already frail. We also summarise the evidence linking immunosenescence, inflammation and endocrine changes to frailty and investigate whether targeted drug therapy has the potential to influence frailty pathophysiology. PMID:23141547

  4. 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.

  5. Electrophysiological Basis for the Antiarrhythmic Actions of Ranolazine

    OpenAIRE

    Antzelevitch, Charles; Burashnikov, Alexander; Sicouri, Serge; Belardinelli, Luiz

    2011-01-01

    Ranolazine is an FDA-approved anti-anginal agent. Experimental and clinical studies have shown that ranolazine has anti-arrhythmic effects in both ventricles and atria. In the ventricles, ranolazine can suppress arrhythmias associated with acute coronary syndrome, long QT, heart failure, ischemia, and reperfusion. In atria, ranolazine effectively suppresses atrial tachyarrhythmias and fibrillation (AF). Recent studies have shown that the drug may be effective and safe in suppressing AF when u...

  6. Acupuncture therapy for drug addiction.

    Science.gov (United States)

    Motlagh, Farid Esmaeili; Ibrahim, Fatimah; Rashid, Rusdi Abd; Seghatoleslam, Tahereh; Habil, Hussain

    2016-01-01

    Acupuncture therapy has been used to treat substance abuse. This study aims to review experimental studies examining the effects of acupuncture on addiction. Research and review articles on acupuncture treatment of substance abuse published between January 2000 and September 2014 were searched using the databases ISI Web of Science Core Collection and EBSCO's MEDLINE Complete. Clinical trial studies on the efficacy of acupuncture therapy for substance abuse were classified according to substance (cocaine, opioid, nicotine, and alcohol), and their treatment protocols, assessments, and findings were examined. A total of 119 studies were identified, of which 85 research articles addressed the efficacy of acupuncture for treating addiction. There were substantial variations in study protocols, particularly regarding treatment duration, frequency of electroacupuncture, duration of stimulation, and choice of acupoints. Contradictory results, intergroup differences, variation in sample sizes, and acupuncture placebo effects made it difficult to evaluate acupuncture effectiveness in drug addiction treatment. This review also identified a lack of rigorous study design, such as control of confounding variables by incorporating sham controls, sufficient sample sizes, reliable assessments, and adequately replicated experiments. PMID:27053944

  7. Qtc interval as a guide to select those patients with congestive heart failure and reduced left ventricular systolic function who will benefit from antiarrhythmic treatment with dofetilide

    DEFF Research Database (Denmark)

    Brendorp, B; Elming, H; Jun, L;

    2001-01-01

    BACKGROUND: A prolonged QTc interval is considered a contraindication for class III antiarrhythmic drugs, but the influence of a normal or a slightly increased baseline QTc interval on the risk or benefit of treatment with a class III antiarrhythmic drug is not sufficiently clarified. METHODS AND...

  8. 植入ICD的患者均需使用抗心律失常药吗?%Antiarrhythmic Drugs for All Patients With an ICD?

    Institute of Scientific and Technical Information of China (English)

    Richard L. Page; 王琳

    2007-01-01

    通常认为,在应用植入式复律除颤器(implantable cardioverter defibrillator,ICD)早期联合应用抗心律失常药物是多余的,这就像用了腰带又加吊带。直到不久前人们才发现,随着时间的推移,许多病人最终仍需在ICD的基础上使用抗心律失常药。在JAMA杂志中,Connolly及其同事报告了“植入式复律除颤器病人最佳药物治疗试验”(Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients,OPTIC)。他们提出这样一个问题,即在植入ICD时是否应该应用抗心律失常药物并加上一种β-阻滞剂,以减少ICD放电。为了回答这个问题,关键是要了解ICD和抗心律失常药物的相互作用以及联合应用的效果。

  9. Understanding Side Effects of Drug Therapy

    Science.gov (United States)

    ... by drug therapy. Low-fat dairy products like milk, cottage cheese and yogurt also supply a good amount of protein and calcium, along with other important vitamins and minerals. People living with cancer have different nutrition goals ...

  10. Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Galpin, Jason D; Frankel, Adam; Ahern, Christopher A

    2011-01-01

    Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan-Williams cl...

  11. Drug therapy in spinal tuberculosis

    OpenAIRE

    Rajasekaran, S.; Khandelwal, Gaurav

    2012-01-01

    Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and henc...

  12. PAROXYSMAL ATRIAL FIBRILLATION: CHOICE OF CARDIOVERSION THERAPY

    Directory of Open Access Journals (Sweden)

    B. A. Tatarskii

    2015-12-01

    Full Text Available Characteristics and classification of different patterns of paroxysmal atrial fibrillation are presented. Main indications to restoration of sinus rhythm are discussed. The features of main medications used to terminate of atrial fibrillation are given. The choice of antiarrhythmic drug is considerate. Necessity of individual approach to therapy tactics is proved.

  13. Acupuncture therapy for drug addiction

    OpenAIRE

    Motlagh, Farid Esmaeili; Ibrahim, Fatimah; Rashid , Rusdi Abd.; SEGHATOLESLAM, Tahereh; Habil, Hussain

    2016-01-01

    Acupuncture therapy has been used to treat substance abuse. This study aims to review experimental studies examining the effects of acupuncture on addiction. Research and review articles on acupuncture treatment of substance abuse published between January 2000 and September 2014 were searched using the databases ISI Web of Science Core Collection and EBSCO’s MEDLINE Complete. Clinical trial studies on the efficacy of acupuncture therapy for substance abuse were classified according to substa...

  14. HIV-1 Antiretroviral Drug Therapy

    OpenAIRE

    Arts, Eric J.; Hazuda, Daria J.

    2012-01-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with ...

  15. [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...

  16. Fracture healing and drug therapies in osteoporosis

    OpenAIRE

    Hoang-Kim, Amy; Gelsomini, Letizia; Luciani, Deianira; Moroni, Antonio; Giannini, Sandro

    2009-01-01

    Fracture repair has not been fully optimised and there is opportunity to increase the healing rate and reduce the number of complications using pharmacological means. While most anti-osteoporosis drugs have been widely tested for their ability to decrease the risk of osteoporotic fractures, fragility fractures still occur in patients under medical intervention. The primary purpose of this systematic review is to understand these underlying mechanisms between bone and drug therapies in osteopo...

  17. 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.

  18. A New Anti-arrhythmic Agent Developed

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ In cooperation with colleagues from the China Pharmaceutical University over the past 15 years, researchers from the Shanghai Institute of Materia Medica (SIMM), a pharmaceutical research arm of CAS, have developed a new injection of acehytisine hydrochloride as a natural medication against heart rhythm disorders. The drug was officially approved on August 22, 2005 by China's State Food & Drug Administration (SFDA) as a new and marketable pharmaceutical for clinical therapy.

  19. Photodynamic therapy, new drugs, new lasers

    International Nuclear Information System (INIS)

    In the mid-1970's Dougherty and co-workers reintroduced hematoporphyrin derivative (HpD) as tumor localizer and photosensitizer for the detection and treatment of neoplastic disease. The efforts of this group led to the introduction of the combination of HpD and lasers for the treatment of a number of human neoplasms. During the late 1970's and throughout most of the 1980's efforts were made to determine the active component in the mixture of porphyrins which comprise HpO. The standard light source used in HpD was the argon-dye laser. Recently new photosensitizers for photodynamic therapy have been introduced. These newer photosensitizers are pure and not mixtures and are associated with less side effects than HpD. Concomitant with the development of new photosensitizers has been the development of new laser systems for photodynamic therapy. In this paper current developments in new drugs and new lasers for photodynamic therapy are presented

  20. Carbon materials for drug delivery & cancer therapy

    Directory of Open Access Journals (Sweden)

    Zhuang Liu

    2011-07-01

    Full Text Available Carbon nanotubes and graphene are both low-dimensional sp2 carbon nanomaterials exhibiting many unique physical and chemical properties that are interesting in a wide range of areas including nanomedicine. Since 2004, carbon nanotubes have been extensively explored as drug delivery carriers for the intracellular transport of chemotherapy drugs, proteins, and genes. In vivo cancer treatment with carbon nanotubes has been demonstrated in animal experiments by several different groups. Recently, graphene, another allotrope of carbon, has also shown promise in various biomedical applications. In this article, we will highlight recent research on these two categories of closely related carbon nanomaterials for applications in drug delivery and cancer therapy, and discuss the opportunities and challenges in this rapidly growing field.

  1. Potential drug therapy problems on an elderly nursing home population

    OpenAIRE

    Dias Junior, Carlos A.C.; Ribeiro, Andréia; Soares, Adriana C; Pereira, Mariana L.; Nascimento, Mariana M.G.

    2011-01-01

    The elderly population and the incidence of chronic diseases are growing rapidly in Brazil. This raises the demand for health services (like Nursing Homes - NH) and drugs, exposing this population to Potential Drug Therapy Problems (PDTP). A cross-sectional study in a Brazilian NH was developed through prescription analyses. PDTP were accounted when one of the following were detected: double therapy (DT); sub-dose; overdose; drug-drug interaction (DDI); food-drug interaction (FDI); Potentiall...

  2. Drug: D00477 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00477 Drug Procainamide hydrochloride (JP16/USP); Procan SR (TN); Procanbid (TN); ...r agents 212 Antiarrhythmic agents 2121 Procainamides D00477 Procainamide hydrochloride (JP16/USP) Anatomica...TIARRHYTHMICS, CLASS I AND III C01BA Antiarrhythmics, class Ia C01BA02 Procainamide D00477 Procai...namide hydrochloride (JP16/USP) USP drug classification [BR:br08302] Cardiovascular Agents Antiarrhythmics Procai...namide D00477 Procainamide hydrochloride (JP16/USP) Target-based classification of drug

  3. Drug-therapy networks and the predictions of novel drug targets

    OpenAIRE

    Spiro, Zoltan; Kovacs, Istvan A.; Csermely, Peter

    2008-01-01

    Recently, a number of drug-therapy, disease, drug, and drug-target networks have been introduced. Here we suggest novel methods for network-based prediction of novel drug targets and for improvement of drug efficiency by analysing the effects of drugs on the robustness of cellular networks.

  4. 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. PMID:25561484

  5. [Metabolomics has the potential to improve drug therapy.

    Science.gov (United States)

    Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder; Rasmussen, Henrik Berg

    2014-03-17

    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 "individualized". In this chase metabolomics is a hot topic. The aim of this paper is to review the concepts of metabolomics and the possible applications in regard to drug development, drug therapy and diagnosis, prognosis and monitoring of diseases. PMID:25096206

  6. Metabolomics has the potential to improve drug therapy

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder; Rasmussen, Henrik Berg

    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 mor...... "individualized". In this chase metabolomics is a hot topic. The aim of this paper is to review the concepts of metabolomics and the possible applications in regard to drug development, drug therapy and diagnosis, prognosis and monitoring of diseases....

  7. Drug therapy in cardiac arrest: a review of the literature.

    Science.gov (United States)

    Lundin, Andreas; Djärv, Therese; Engdahl, Johan; Hollenberg, Jacob; Nordberg, Per; Ravn-Fischer, Annika; Ringh, Mattias; Rysz, Susanne; Svensson, Leif; Herlitz, Johan; Lundgren, Peter

    2016-01-01

    The aim of this study was to review the literature on human studies of drug therapy in cardiac arrest during the last 25 years. In May 2015, a systematic literature search was performed in PubMed, Embase, the Cochrane Library, and CRD databases. Prospective interventional and observational studies evaluating a specified drug therapy in human cardiac arrest reporting a clinical endpoint [i.e. return of spontaneous circulation (ROSC) or survival] and published in English 1990 or later were included, whereas animal studies, case series and reports, studies of drug administration, drug pharmacology, non-specified drug therapies, preventive drug therapy, drug administration after ROSC, studies with primarily physiological endpoints, and studies of traumatic cardiac arrest were excluded. The literature search identified a total of 8936 articles. Eighty-eight articles met our inclusion criteria and were included in the review. We identified no human study in which drug therapy, compared with placebo, improved long-term survival. Regarding adrenaline and amiodarone, the drugs currently recommended in cardiac arrest, two prospective randomized placebo-controlled trials, were identified for adrenaline, and one for amiodarone, but they were all underpowered to detect differences in survival to hospital discharge. Of all reviewed studies, only one recent prospective study demonstrated improved neurological outcome with one therapy over another using a combination of vasopressin, steroids, and adrenaline as the intervention compared with standard adrenaline administration. The evidence base for drug therapy in cardiac arrest is scarce. However, many human studies on drug therapy in cardiac arrest have not been powered to identify differences in important clinical outcomes such as survival to hospital discharge and favourable neurological outcome. Efforts are needed to initiate large multicentre prospective randomized clinical trials to evaluate both currently recommended and

  8. Drug: D06172 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06172 Drug Tocainide (USAN/INN) C11H16N2O 192.1263 192.2575 D06172.gif Cardiac dep...01 CARDIAC THERAPY C01B ANTIARRHYTHMICS, CLASS I AND III C01BB Antiarrhythmics, class Ib C01BB03 Tocainide D06172 Tocai...HSA:6323] [KO:K04833] Tocainide [ATC:C01BB03] D06172 Tocainide (USAN/INN) voltage-gated sodium channel (SCN2...A) [HSA:6326] [KO:K04834] Tocainide [ATC:C01BB03] D06172 Tocainide (USAN/INN) voltage-gated sodium channel (...SCN3A) [HSA:6328] [KO:K04836] Tocainide [ATC:C01BB03] D06172 Tocainide (USAN/INN)

  9. Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts.

    Directory of Open Access Journals (Sweden)

    Yun-Ping Lim

    Full Text Available The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD.We used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010. We identified an additional 19,497 patients with antiarrhythmic history in the same period who did not develop MNLIHD and were frequency-matched using age, sex, and index year to form a control group. Five commercially available antiarrhythmic agents, amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.The adjusted odds ratio (OR of MNLIHD was 1.60 (95% confidence interval [CI], 1.45-1.77 for amiodarone users versus nonamiodarone users. In subgroup analysis, amiodarone use was significantly associated with an increased risk of MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5 for patients with comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06 for those without comorbidities. After adjustment for age, sex, statins, anti-diabetes medications, non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with annual mean defined daily doses of ≤ 30, 31-145, and >145, respectively.The results of the present study indicated that amiodarone might be associated with the development of MNLIHD in a dose-dependent manner, particularly among patients with comorbidities.

  10. [PRINCIPLES OF POSTOPERATIVE DRUG THERAPY OF COMPLICATED DUODENAL ULCERS].

    Science.gov (United States)

    Denisova, E V; Nazarov, V E

    2015-01-01

    The article highlights the principles of individualized drug therapy of complicated duodenal ulcers in the postoperative period, based on the removal of the pathophysiological changes that occurred after different types of medical or surgical benefits. PMID:26415272

  11. POTASSIUM CHANNELS AS DRUGS TARGETS IN THERAPY OF CARDIOVASCULAR DESEASES: 25 YEARS LATER

    Directory of Open Access Journals (Sweden)

    Protić Dragana

    2013-01-01

    Full Text Available Potassium channels are the most variable ion channel group. They participate in numerous cardiovascular functions, for example regulation of vascular tone, maintenance of resting cardiac membrane potential and excitability of cardiac conduction tissue. Both drugs and endogenous ligands could modulate potassium channel function, belonging to the potassium channel blockers or openers. Modulation of potassium channels could be a therapeutic or adverse drug action. Class III antiarrhythmic agents block the potassium channels, thereby prolonging repolarization phase of action potential with resulting prolongation of effective refractory period. Their effectiveness against supraventricular and ventricular arrhythmias should be weighted against their proarrhythmogenic potential. In addition, numerous other antiarrhythmic agents could modulate potassium channels as well. Diazoxide, minoxidil and nicorandil (well known arterial vasodilators, as well as numerous newly synthesized substances with still unknown therapeutic potential, belong to the potassium channel activators/ openers. Therapeutic use of such vasodilators may involve treatment of hypertension (diazoxide, minoxidil and stable angina (nicorandil. Their use might be accompanied with side effects, such as vasodilation, edema, hypotension and reflex tachycardia. Potassium channel openers have also an important role in the treatment of peripheral vascular disease and pulmonary hypertension. In the future, drugs with selective effects on the vascular or cardiac potassium channels could be useful therapeutic agents.

  12. Drug addiction therapy. A dance to the music of time.

    Science.gov (United States)

    Goodison, L; Schafer, H

    1999-10-21

    Dance therapy can play a useful role in the treatment and rehabilitation of women with drug addiction. It works by raising self-esteem through an improved relationship with the body, giving women the strength to help combat their habit. The benefits of dance therapy for women at the detox unit of Holloway Prison have been confirmed by prison staff. PMID:10662323

  13. Bone scintigraphy during therapy with cytostatically acting drugs

    International Nuclear Information System (INIS)

    Case reports show up, that bone scintigraphy during therapy of metastasing cancer of mamma or prostata with cytostatically acting drugs may reveal 'pseudonormal' results. False negative diagnosis can be excluded only by carefully regarding drug history. Gamma-camera with wholebody scan device for scintigraphy in two projections simplifies safe evaluation significantly. (orig.)

  14. Liposomal drug delivery in multimodal cancer therapy

    OpenAIRE

    2011-01-01

    Encapsulating cytostatics into lipid vesicles, i.e. liposomes, improves tumour drug accumulation and reduce adverse effects. Liposomal doxorubicin (DXR) has been used in the treatment of a variety of cancers and may also be suitable for combining with other treatment modalities. By modulating liposomal membranes, liposomes can be made ultrasound (US) sensitive releasing encapsulated drug in tumour tissue upon external US stimulation and may thereby improve therapeutic outcome. Moreover, as DX...

  15. Public health implications of antiretroviral therapy and HIV drug resistance.

    Science.gov (United States)

    Wainberg, M A; Friedland, G

    1998-06-24

    Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy. PMID:9643862

  16. Drug therapy for obesity in the elderly.

    Science.gov (United States)

    Dvorak, R; Starling, R D; Callés-Escandon, J; Sims, E A; Poehlman, E T

    1997-11-01

    The prevalence of obesity is increasing rapidly in the US and other developed countries. Even though the percentage of older individuals is increasing worldwide, obesity has only recently become a recognised problem in this population. Obesity occurs when energy intake chronically exceeds energy expenditure. Moreover, advancing age is associated with an inability to couple energy intake with energy expenditure. Obesity contributes to many adverse health outcomes, including non-insulin-dependent (type II) diabetes mellitus, as well as to an increase in both cardiovascular and all-cause mortality. Only recently has the medical community begun to accept obesity as a disease with a multifactorial pathogenesis that requires systematic lifestyle changes and pharmacological treatment. Several groups of drugs are available for the pharmacotherapy of obesity; anorectic medications (e.g. fenfluramine, dexfenfluramine); substances affecting energy expenditure and body composition [e.g. chromium (chromium picolinate), ephedrine, anabolic steroids, beta 3-adrenoceptor agonists]; and drugs affecting the absorption of nutrients (e.g. orlistat). To date, few drugs have produced and sustained a significant bodyweight loss. However, some drugs induce a significant short term reduction in bodyweight compared with placebo. Moreover, there is a paucity of information regarding the effectiveness of these drugs in the treatment of obesity in the elderly. Furthermore, it is even debated whether obesity should be treated with drug intervention in the elderly. Clinicians prescribing medications for obesity treatment in the elderly need to carefully consider the benefit: risk ratio, given the high prevalence of polypharmacy in elderly patients. Furthermore, physiological changes that occur with aging may affect the pharmacokinetics of administered drugs and need to be taken into consideration. PMID:9359021

  17. Drug loaded magnetic nanoparticles for cancer therapy

    International Nuclear Information System (INIS)

    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

  18. Immunoprotective therapy with targeted anticancer drugs

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka; Strohalm, Jiří; Hoste, K.; Jelínková, Markéta; Hovorka, Ondřej; Kovář, Marek; Plocová, Daniela; Šírová, Milada; Šťastný, Marek; Ulbrich, Karel

    2001-01-01

    Roč. 172, - (2001), s. 21-28. ISSN 1022-1360 R&D Projects: GA ČR GV307/96/K226; GA MZd NC5050 Institutional research plan: CEZ:AV0Z5020903 Keywords : doxorubicin * mitomycin * immunoprotective therapy Subject RIV: EC - Immunology Impact factor: 0.634, year: 2001

  19. 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 pat

  20. Progress in drug therapies for HIV infection.

    OpenAIRE

    Broder, S; Fauci, A S

    1988-01-01

    The discovery of effective therapies for HIV requires a fundamental knowledge of retroviral infections. Research by the Public Health Service and collaborating organizations on oncogenic viruses, including retroviruses, has provided much of the basic understanding of retroviruses in general and anti-retroviral therapeutic strategies in particular. Early work by the Viral Cancer and Developmental Therapeutic Programs of the National Cancer Institute and the Intramural Research Program of the N...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... 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......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...

  2. Treating Women Drug Abusers: Action Therapy and Trauma Assessment

    OpenAIRE

    Uhler, Ann S.; Parker, Olga V.

    2002-01-01

    The authors suggest that action therapy, a group of techniques including psychodrama, drama therapy, and role training, warrants research attention to determine whether it is well suited to the special characteristics and needs of women clients. In addition, the authors call on researchers to develop a new standardized tool for counselors to use during initial interviews to determine whether women presenting for drug abuse treatment also have significant issues related to trauma. The authors ...

  3. [Driving fitness in therapy with antidepressive drugs].

    Science.gov (United States)

    Soyka, M; Dittert, S; Gartenmeier, A; Schäfer, M

    1998-04-01

    The driving ability of patients under therapy with antidepressives is seen less restrictive than some years ago. The inhibition of psychomotor performance is of special interest. Some empirical studies point at antidepressives increasing the risk for accidents at least in elderly patients. Different groups of antidepressants apparently show different effects. Tricyclic antidepressants were shown to worsen cognitive and psychomotor performance in some patients while serotonin reuptake inhibitors and some other new antidepressants may cause less behavioral toxicity. Methodological problems in assessing driving ability and some recent findings are discussed. PMID:9587241

  4. 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.

  5. Totally drug-resistant tuberculosis and adjunct therapies.

    Science.gov (United States)

    Parida, S K; Axelsson-Robertson, R; Rao, M V; Singh, N; Master, I; Lutckii, A; Keshavjee, S; Andersson, J; Zumla, A; Maeurer, M

    2015-04-01

    The first cases of totally drug-resistant (TDR) tuberculosis (TB) were reported in Italy 10 years ago; more recently, cases have also been reported in Iran, India and South Africa. Although there is no consensus on terminology, it is most commonly described as 'resistance to all first- and second-line drugs used to treat TB'. Mycobacterium tuberculosis (M.tb) acquires drug resistance mutations in a sequential fashion under suboptimal drug pressure due to monotherapy, inadequate dosing, treatment interruptions and drug interactions. The treatment of TDR-TB includes antibiotics with disputed or minimal effectiveness against M.tb, and the fatality rate is high. Comorbidities such as diabetes and infection with human immunodeficiency virus further impact on TB treatment options and survival rates. Several new drug candidates with novel modes of action are under late-stage clinical evaluation (e.g., delamanid, bedaquiline, SQ109 and sutezolid). 'Repurposed' antibiotics have also recently been included in the treatment of extensively drug resistant TB. However, because of mutations in M.tb, drugs will not provide a cure for TB in the long term. Adjunct TB therapies, including therapeutic vaccines, vitamin supplementation and/or repurposing of drugs targeting biologically and clinically relevant molecular pathways, may achieve better clinical outcomes in combination with standard chemotherapy. Here, we review broader perspectives of drug resistance in TB and potential adjunct treatment options. PMID:24809736

  6. Drug therapy of attention deficit hyperactivity disorder: Current trends

    Directory of Open Access Journals (Sweden)

    Avinash De Sousa

    2012-01-01

    Full Text Available Attention deficit hyperactivity disorder is a developmental disorder with an age onset prior to 7 years. Children with ADHD have significantly lower ability to focus and sustain attention and also score higher on impulsivity and hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of ADHD treatment for decades with evidence supporting their use. However, recent years have seen emergence of newer drugs and drug delivery systems, like osmotic release oral systems and transdermal patches, to mention a few. The use of nonstimulant drugs like atomoxetine and various other drugs, such as a-agonists, and a few antidepressants, being used in an off-label manner, have added to the pharmacotherapy of ADHD. This review discusses current trends in drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the future.

  7. Drug Therapy for Small Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Ramachandran Meenakshisundaram

    2010-03-01

    Full Text Available Abdominal aortic aneurysm is often asymptomatic, less recognized, and causes considerable mortalityand morbidity, if missed. The incidence varies from country to country and the occurrence is influencedby modifiable (smoking, coronary heart disease, hypertension, dyslipidemia, and prolonged steroid therapyand non-modifiable risk factors (increasing age, male gender, and positive family history. Most ofthe patients with such aneurysm do not exhibit symptoms and the diagnosis is made accidentally duringroutine medical investigations, abdominal ultrasonography, or by an astute surgeon during an abdominalprocedure. Sometimes the diagnosis is made in an emergency room, if the attending resident/doctor isaware of it. Despite good diagnosis and effective management, the outcomes of complicated cases arepoor and the treatment cost is prohibitive. Hence, we reviewed the literature to find out the pathogenesisof such aneurysms and the usefulness of available drugs in its prevention.

  8. ANALYSIS OF PRESCRIPTION PATTERN AND DRUG UTILIZATION IN ASTHMA THERAPY

    Directory of Open Access Journals (Sweden)

    Patel Pinal D.

    2012-07-01

    Full Text Available This drug utilization or prescription-monitoring study was conducted to evaluate the drug-prescribing trend of anti-asthmatic drugs in retailed pharmacy outlets during 2009 and 2011 in urban and rural area of Saurashtra region, Gujarat, India. The study was conducted on 601 patients, using a developed prescription auditing Performa. Data was recorded from the co-operating patients by interviewing and information was filled in the performa. The data suggested that punctuality in professionalism like mentioning own (physicians name, patients name, diagnosis and minimum qualification of MD/MS was observed to be higher in urban than the rural. There was no significant sex difference. Bronchial asthma was found to be more prevalent in the age group 41 to 60 years. Patients were found to consult the doctor 2 to 7 days after symptoms and pay consulting fee more than Rs.20=00. The collected information suggested that bronchodilators were the most frequently prescribed anti-asthmatic drugs followed by corticosteroids and methylxanthine preparation. Analysis of prescription revealed that multiple drug therapy was opted for a significant number of patients as compared to single drug therapy. In combination therapy, the three-drug combination was the most often prescribed. Number of partial purchase of drugs as per the prescriptions was found to be higher in rural area than urban area. Lack of money was one of the reasons for partial prescription. Thus, it can be concluded that the present prescribing pattern of antiasthmatics in Saurashtra region does not completely meet standard guidelines for the asthma treatment. Hence there is a need of awareness amongst the physicians of Saurashtra region so that they can follow the guidelines while treating asthma. Also the patients must be encouraged to complete whole treatment for improving the health. It has been also concluded that a study may be more meaningful to further improve the dispensing practices of the

  9. Cardiovascular safety monitoring during oncology drug development and therapy.

    Science.gov (United States)

    Turner, J Rick; Panicker, Gopi Krishna; Karnad, Dilip R; Cabell, Christopher H; Lieberman, Ronald; Kothari, Snehal

    2014-01-01

    Assessments of cardiac and cardiovascular toxicity are prominent components of drug safety endeavors during drug development and clinical practice. Oncologic drugs bring several challenges to both domains. First, during drug development, it is necessary to adapt the ICH E14 "Thorough QT/QTc Study" because the cytotoxic nature of many oncologics precludes their being administered to healthy individuals. Second, appropriate benefit-risk assessments must be made by regulators: given the benefit these drugs provide in life-threatening illnesses, a greater degree of risk may be acceptable when granting marketing authorization than for drugs for less severe indications. Third, considerable clinical consideration is needed for patients who are receiving and have finished receiving pharmacotherapy. Paradoxically, although such therapy has proved very successful in many cases, with disease states going into remission and patients living for many years after cessation of treatment, cardiotoxicities can manifest themselves relatively soon or up to a decade later. Oncologic drugs have been associated with various off-target cardiovascular responses, including cardiomyopathy leading to heart failure, cardiac dysrhythmias, thromboembolic events, and hypertension. Follow-up attention and care are, therefore, critical. This article reviews the process of benefit-risk estimation, provides an overview of nonclinical and preapproval clinical assessment of cardiovascular safety of oncology drugs, and discusses strategies for monitoring and management of patients receiving drugs with known cardiotoxicity risk. These measures include cardiac function monitoring, limitation of chemotherapy dose, use of anthracycline analogs and cardioprotectants, and early detection of myocardial cell injury using biomarkers. PMID:24451296

  10. [Cost reducing of or by drugs. More rationality and efficiency in drug therapy].

    Science.gov (United States)

    Glaeske, G

    2010-08-01

    The expenditure incurred in the German statutory health insurance (SHI) in relation to drugs, are characterized not only by the amount of drug prices, but also by their degree of efficient usage. The prevention of superfluous and inappropriate pharmaceutical supply leads to direct savings in expenditure, a drug-based guideline-oriented therapy, and prevention of diseases and deficiency symptoms leads to savings by avoiding hospitalizations, operations, and maintaining the ability to work. Prescriptions of new and expensive me-too drugs with no additional benefit bind financial resources of the SHI, which should be available for pharmaceutical therapeutic innovations. PMID:20552155

  11. Bioinformatics in cancer therapy and drug design

    International Nuclear Information System (INIS)

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  12. Echinocandins: A ray of hope in antifungal drug therapy

    Directory of Open Access Journals (Sweden)

    Grover Neeta

    2010-01-01

    Full Text Available Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall. Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis. The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.

  13. Iatrogenic disease: a hazard of multiple drug therapy.

    Science.gov (United States)

    D'Arcy, P F

    1976-12-01

    The term ''iatrogenic disease'' means disease caused by therapy prescribed by doctors. Most such diseases are drug induced. Adverse effects of drugs have been more common in seriously ill patients who have received many drugs. Drug interaction has often been the cause. Most have been dose-related from cumulative pharmacologic effects. Reported data have been incomplete. Individual variability due to a genetic basis has been a factor. Environmental influences, such as smoking, atmospheric pollution, and hardness of the water supply may be involved. Sometimes the patient's metabolism has been impaired by concomitant liver or kidney malfunction. In such cases the drug, or its metabolites, may build up to a toxic level. A lowered threshold to the normal action of a drug is frequent among the very old and the very young. Geriatric patients have a considerable reduction in the reserve capacity of many organs. Hypersensitivity to a drug may be present. Skin rashes and eruptions are most common in this type of allergic reaction although jaundice and hemolytic anemia have followed. Polypharmacy increases the risk. Some patients make errors in taking prescribed drugs. Also, additional self-medication is common. Drug-food interactions may occur. Needed vitamins may be absorbed and eliminated by the use of liquid paraffin as a laxative. Intestinal flora-destroying antibiotics permit other organisms to grow. Alcohol is an additional hazard. Oral contraceptive use may be followed by anemia, and may react with other drugs. A list of such known reactions is given. Delayed iatrogenic neoplasia is being considered. Effects on the progeny have been shown with several drugs. Forewarning creates awareness and caution. PMID:798237

  14. Antiarrhythmic Mechanisms of SK Channel Inhibition in the Rat Atrium

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Wang, Xiaodong; Axelsen, Lene Nygaard;

    2015-01-01

    period (ERP) and slowing the conduction velocity. We therefore aimed at elucidating these properties of SK channel inhibition and the underlying antiarrhythmic mechanisms by using; microelectrode action potential recordings and conduction velocity measurements in isolated rat atrium. Automated patch-clamping...... and two-electrode voltage-clamp was used to access INa and IK,ACh respectively. RESULTS: The SK channel inhibitor N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) exhibited antiarrhythmic effects. ICA prevented electrically induced runs of atrial fibrillation in the isolated right atrium and...... channel inhibition by ICA (10-30 µM) demonstrated prominent depression of other sodium channel-dependent parameters. ICA did not inhibit IK,ACh, but at concentrations above 10 µM ICA use-dependently inhibited INa. CONCLUSION: SK channel inhibition modulates multiple parameters of the action potential. It...

  15. Pulmonary fibrosis associated with psychotropic drug therapy: a case report

    Directory of Open Access Journals (Sweden)

    Thornton Clare

    2009-11-01

    Full Text Available Abstract Introduction Sertraline and Risperidone are commonly used psychotropic drugs. Sertraline has previously been associated with eosinopilic pneumonia. Neither drug is recognised as a cause of diffuse fibrotic lung disease. Our report represents the first such case. Case Presentation We describe the case of a 33 year old Asian male with chronic schizophrenia who had been treated for three years with sertraline and risperidone. He presented to hospital in respiratory failure following a six month history of progressive breathlessness. High resolution CT scan demonstrated diffuse pulmonary fibrosis admixed with patchy areas of consolidation. Because the aetiology of this man's diffuse parenchymal lung disease remained unclear a surgical lung biopsy was undertaken. Histological assessment disclosed widespread fibrosis with marked eosinophillic infiltration and associated organising pneumonia - features all highly suggestive of drug induced lung disease. Following withdrawal of both sertraline and risperidone and initiation of corticosteroid therapy the patient's respiratory failure resolved and three years later he remains well albeit limited by breathlessness on heavy exertion. Conclusion Drug induced lung disease can be rapidly progressive and if drug exposure continues may result in respiratory failure and death. Prompt recognition is critical as drug withdrawal may result in marked resolution of disease. This case highlights sertraline and risperidone as drugs that may, in susceptible individuals, cause diffuse pulmonary fibrosis.

  16. 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.

  17. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Walfridsson, H; Walfridsson, U; Nielsen, J Cosedis;

    2015-01-01

    AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In...... made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported...... improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211....

  18. 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.

  19. Catheter Ablation as First-Line Therapy for Atrial Fibrillation: Ready for Prime-Time?

    Science.gov (United States)

    Carrizo, Aldo G; Morillo, Carlos A

    2016-07-01

    Current guidelines include atrial fibrillation (AF) catheter ablation as part of the management strategy in patients that have failed at least one oral antiarrhythmic drug treatment course. However, growing evidence derived from both randomized and non-randomized studies demonstrate lower rates of AF recurrence and AF burden in patients with paroxysmal AF that are naïve to antiarrhythmic drug treatment. Furthermore, progression from paroxysmal AF to persistent AF appears to be delayed by early catheter ablation of AF. The current review addresses the question of the best timing for ablation in patients with paroxysmal AF and provides the rationale for offering AF ablation as first-line therapy based on the most updated evidence available. PMID:27300744

  20. Magnetic nanoparticle-based drug delivery for cancer therapy.

    Science.gov (United States)

    Tietze, Rainer; Zaloga, Jan; Unterweger, Harald; Lyer, Stefan; Friedrich, Ralf P; Janko, Christina; Pöttler, Marina; Dürr, Stephan; Alexiou, Christoph

    2015-12-18

    Nanoparticles have belonged to various fields of biomedical research for quite some time. A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles which are directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium [1]. In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so-called "magnetic drug targeting", MDT), has additionally emerged as a promising strategy of drug delivery. Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism-exploiting, tumor-specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. As it is nearly impossible to record every magnetic nanoparticle system developed so far, this review summarizes interesting approaches which have recently emerged in the field of targeted drug delivery for cancer therapy based on magnetic nanoparticles. PMID:26271592

  1. Surgical radiation and drug therapy of breast cancer

    International Nuclear Information System (INIS)

    There main components of the program of radical therapy of breast cancer are distinguished: surgical, radiation and drug. The surgical operation continues to be one of the main therapeutic methods, though there is a trend towards limitation of the amount of surgical interventions. Investigations are carried out in the performance of rational operations of the cancer of the 1 and 2 stages supplemented with pre- and postoperative irradiation. Techniques of large dose fractionation are doveloped. It is shown that in case of 2b and 3a,b stages it is oppropriate to assign a combined or complex therapy: operation, irradiation and chemotherapy. The advantages of polychemotherapy via monochemotherapy are noted. The effect of immunotherapy on the efficiency of the therapy of brest cancer is studied. A conclusion is made that a certain progress has been reached recently in the treatment of breast cancer and that only an individual approach should be used when choosing therapy tactics taking into account all vital factors

  2. Advances in drug therapy for systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Wallace Daniel J

    2010-11-01

    Full Text Available Abstract Systemic lupus erythematosus (SLE is an autoimmune disorder that afflicts 500,000 people in the United States. There has not been a new SLE drug approved in the United States since 1958. However, a guidance document issued by the Food and Drug Administration in 2005 provided a roadmap for investigators which spawned numerous ongoing clinical trials. Among these, Belimumab, a monoclonal antibody to soluble B lymphocyte stimulator, met its primary endpoints in two large trials and will probably obtain FDA approval soon. Other promising agents targeting a variety of mechanisms of action are currently in development. This minireview highlights the latest therapies under investigation in SLE and gives an overview of the pathways that are specifically being targeted.

  3. 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.

  4. Phenytoin as an effective treatment for polymorphic ventricular tachycardia due to QT prolongation in a patient with multiple drug intolerances.

    Science.gov (United States)

    Yager, Neil; Wang, Katherine; Keshwani, Najiba; Torosoff, Mikhail

    2015-01-01

    We present a case of a 69-year-old woman presenting with polymorphic ventricular tachycardia caused by QT prolongation. Owing to known intolerances to a majority of antiarrhythmic medications, one remaining option was to initiate phenytoin. Phenytoin's narrow therapeutic window, multiple drug interactions and side effect profile make it an infrequently used antiarrhythmic. It is, however, a potent antiarrhythmic agent, which may be useful in treatment of ventricular tachycardia, especially in patients with multiple drug intolerances. PMID:26071440

  5. 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. PMID:25148426

  6. Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy.

    Science.gov (United States)

    Abellan-Pose, Raquel; Csaba, Noemi; Alonso, Maria Jose

    2016-01-01

    The lymphatic system represents a major route of dissemination in metastatic cancer. Given the lack of selectivity of conventional chemotherapy to prevent lymphatic metastasis, in the last years there has been a growing interest in the development of nanocarriers showing lymphotropic characteristics. The goal of this lymphotargeting strategy is to facilitate the delivery of anticancer drugs to the lymph node-resident cancer cells, thereby enhancing the effectiveness of the anti-cancer therapies. This article focuses on the nanosystems described so far for the active or passive targeting of oncological drugs to the lymphatic circulation. To understand the design and performance of these nanosystems, we will discuss first the physiology of the lymphatic system and how physiopathological changes associated to tumor growth influence the biodistribution of nanocarriers. Second, we provide evidence on how the tailoring of the physicochemical characteristics of nanosystems, i.e. particle size, surface charge and hydrophilicity, allows the modulation of their access to the lymphatic circulation. Finally, we provide an overview of the relationship between the biodistribution and antimetastatic activity of the nanocarriers loaded with oncological drugs, and illustrate the most promising active targeting approaches investigated so far. PMID:26675222

  7. Drug therapy for advanced-stage liver cancer.

    Science.gov (United States)

    Peck-Radosavljevic, Markus

    2014-05-01

    Liver cancer was traditionally treated by surgery or interventional ablative treatments, or, if these options were not feasible, by best supportive care. Since 2008, systemic therapy with the multikinase inhibitor sorafenib has become available worldwide and has become the standard of care for unresectable/non-ablatable or advanced-stage hepatocellular carcinoma (HCC). Sorafenib is able to improve the median overall survival by approximately 3 months. Despite this significant advance in the non-surgical/non-interventional management of liver cancer, this improvement in overall survival is only a first step toward more potent, more targeted, and better tolerated oral antitumor treatments. Since the introduction of sorafenib into clinical practice, several attempts have been made to develop even more effective first-line treatments as well as an effective second-line treatment for HCC. None of these endeavors has been successful so far. The development of drug treatments for HCC has been particularly hampered by the unfortunate push to establish the diagnosis of liver cancer by non-invasive imaging alone, without requiring a liver biopsy for histologic confirmation: this precluded the very necessary search for informative biomarkers and the search for molecular targets for drug development in HCC. This important drawback is being increasingly recognized and corrected. Despite several obstacles remaining to be overcome, it seems reasonable to assume that using a rational, data-driven approach, we will be able to develop better drug treatments for liver cancer in the coming years. PMID:24945003

  8. Evaluating the Safety of Intraoperative Antiarrhythmics in Pediatric Cardiac Surgery Patients.

    Science.gov (United States)

    Beaty, Rachel S; Moffett, Brady S; Hall, Stuart; Kim, Jeffrey

    2015-10-01

    Cardiac arrhythmias occurring during the intraoperative period for cardiac surgery have been associated with excess morbidity and mortality. Several antiarrhythmics have been utilized for the management of intraoperative arrhythmias. These antiarrhythmic medications can cause undesirable adverse outcomes in the intensive care setting. The incidence and treatment of adult intraoperative arrhythmias have been studied. In addition, the prevalence, risk factors, and optimal treatment of pediatric postoperative arrhythmias have also been studied. However, the literature has not been published on intraoperative antiarrhythmia treatment during pediatric cardiac surgery. The purpose of this study was to determine the safety of intraoperative antiarrhythmic medications utilized in pediatric cardiac surgery patients. This was a retrospective review of all patients who received an intraoperative antiarrhythmic in the cardiovascular operating room at Texas Children's Hospital. Patients were included if they underwent cardiovascular surgery from November 2008 to July 2013 and were excluded if antiarrhythmics were given intraoperatively for other indications (i.e., esmolol for hypertension) or if patients were older than 18 years of age. Safety of antiarrhythmic treatment was determined by the absence or presence of adverse events. Control or recurrence of the arrhythmia was analyzed as a secondary measure to help determine antiarrhythmic efficacy. A total of 45 patients were identified (53.3 % male). Patients were a median of 0.52 years at the time of surgery. Primary surgery types were tetralogy of Fallot repair (n = 6; 13.3 %) and ventricular septal defect closure (n = 5, 11.1 %). Thirty-one patients (68.9 %) had documented adverse events after the administration of antiarrhythmics. Most of these adverse events occurred after the administration of amiodarone (n = 16; 51.6 %) followed by esmolol (n = 15; 48.4 %). Fifty-one percent of the arrhythmias resolved in the operating

  9. DRUG THERAPY OF PAROXYSMAL ATRIAL FIBRILLATION IN THE ELDERLY OVER 75 YEARS OLD

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the effectiveness and safety of various agents on paroxysmal atrial fibrillation in the elderly over 75 years old.Methods Totally 264 in-patients (75-91 years old, 185 males and 79 females) with atrial fibrillation history of less than 7 days were enrolled in this study. A total of 611 atrial fibrillation episodes were recorded, but 130 episodes (22. 3% ) of atrial fibrillation were auto-converted to sinus rhythm. The rest 481 episodes of atrial fibrillation were divided into six groups based on the drug used. Results The cardioversion ratio of atrial fibrillation were 9. 5%, 46.9%, 71.7%, 55.9%, 32.7%, and73.6%in control, cedilanid, amiodarone, propafenone, verapamil, and quinidine groups, respectively. Ventricular rate control were 5.4%, 83.6%, 84. 9%, 77.9%, 78.8%, and 11.3% in those groups, respectively. The total effective rates of amiodarone and cedilanid groups were the highest. When the ventricular rate was controlled to below 90 bpm, the patients would almost complain of no discomfort. No severe side-effect was observed in each group. Conclusion Amiodarone and cedilanid may be the proper drugs for the treatment of paroxysmal atrial fibrillation in the elderly. The above antiarrhythmics in each therapeutic group were relatively safe and effective.

  10. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system.

    Science.gov (United States)

    Faiss, S; Scherübl, H; Riecken, E O; Wiedenmann, B

    1996-01-01

    Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration. PMID:8893342

  11. Clinical evaluation of two strategies for improving patient recall of prior drug therapy.

    OpenAIRE

    Bellamy, N; Grace, E; Hanna, B.; Grant, E; Tugwell, P.; Buchanan, W W

    1984-01-01

    The ability to recall details of current and prior drug therapy was evaluated in two studies employing a total of 94 patients with inflammatory polyarthritis. Ten per cent of patients were unable to completely recall the names of their current anti-inflammatory drugs and eighty-three per cent of patients to completely recall the details of prior anti-inflammatory drug therapy. Prompting firstly with the proprietary names of drugs and thereafter with a pill board substantially enhanced recall ...

  12. Immune Cells in Cancer Therapy and Drug Delivery

    Science.gov (United States)

    Eyileten, Ceren; Majchrzak, Kinga; Pilch, Zofia; Tonecka, Katarzyna; Mucha, Joanna; Taciak, Bartlomiej; Ulewicz, Katarzyna; Witt, Katarzyna; Boffi, Alberto; Krol, Magdalena; Rygiel, Tomasz P.

    2016-01-01

    Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacity in vivo as evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment. PMID:27212807

  13. Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

    Science.gov (United States)

    Masood, Farha

    2016-03-01

    A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. PMID:26706565

  14. [Dementia of the Alzheimer type: non-drug and drug therapy].

    Science.gov (United States)

    Kressig, Reto W

    2015-04-01

    The optimal management of Alzheimer's disease (AD) involves a close alliance with AD caregivers and requires early diagnosis, multimodal management, including non-drug and drug interventions, and multispecialty care. Non-pharmacological approaches such as cognitive stimulation programs mostly benefit behavior and psychiatric symptoms in dementia patients. Pharmacologic management of AD consists of eliminating therapeutic redundancies and potentially deleterious medications (Beers Criteria). A pharmacologic foundation of Ginkgo Biloba and combination therapy with a cholinesterase inhibitor and memantine reduces decline in cognition and function, decreases and/or delays the emergence and impact of neuropsychiatric symptoms, postpones institutionalization, and works best when appropriately instituted early and maintained. Despite an existing reimbursement limitation by the health-insurance system in Switzerland, the combination of cholinesterase inhibitor and memantine is possible within the admitted MMSE ranges. PMID:25791046

  15. Non-adherence to drug therapy and drug acquisition costs in a national population - a patient-based register study

    Directory of Open Access Journals (Sweden)

    Hovstadius Bo

    2011-11-01

    Full Text Available Abstract Background Patients' non-adherence to drug therapy is a major problem for society as it is associated with reduced health outcomes. Generally, approximately only 50% of patients with chronic disease in developed countries adhere to prescribed therapy, and the most common non-adherence refers to chronic under-use, i.e. patients use less medication than prescribed or prematurely stop the therapy. Patients' non-adherence leads to high additional costs for society in terms of poor health. Non-adherence is also related to the unnecessary sale of drugs. The aim of the present study was to estimate the drug acquisition cost related to non-adherence to drug therapy in a national population. Methods We constructed a model of the drug acquisition cost related to non-adherence to drug therapy based on patient register data of dispensed out-patient prescriptions in the entire Swedish population during a 12-month period. In the model, the total drug acquisition cost was successively adjusted for the assumed different rates of primary non-adherence (prescriptions not being filled by the patient, and secondary non-adherence (medication not being taken as prescribed according to the patient's age, therapies, and the number of dispensed drugs per patient. Results With an assumption of a general primary non-adherence rate of 3%, and a general secondary non-adherence rate of 50%, for all types of drugs, the acquisition cost related to non-adherence totalled SEK 11.2 billion (€ 1.2 billion, or 48.5% of total drug acquisition costs in Sweden 2006. With the assumption of varying primary non-adherence rates for different age groups and different secondary non-adherence rates for varying types of drug therapies, the acquisition cost related to non-adherence totalled SEK 9.3 billion (€ 1.0 billion, or 40.2% of the total drug acquisition costs. When the assumption of varying primary and secondary non-adherence rates for a different number of dispensed drugs

  16. Non-adherence to drug therapy and drug acquisition costs in a national population - a patient-based register study

    OpenAIRE

    Hovstadius Bo; Petersson Göran

    2011-01-01

    Abstract Background Patients' non-adherence to drug therapy is a major problem for society as it is associated with reduced health outcomes. Generally, approximately only 50% of patients with chronic disease in developed countries adhere to prescribed therapy, and the most common non-adherence refers to chronic under-use, i.e. patients use less medication than prescribed or prematurely stop the therapy. Patients' non-adherence leads to high additional costs for society in terms of poor health...

  17. Individualizing therapy – in search of approaches to maximize the benefit of drug treatment (II)

    OpenAIRE

    Pater Cornel

    2004-01-01

    Abstract Adjusting drug therapy to the individual, a common approach in clinical practice, has evolved from 1) dose adjustments based on clinical effects to 2) dose adjustments made in response to drug levels and, more recently, to 3) dose adjustments based on deoxyribonucleic acid (DNA) sequencing of drug-metabolizing enzyme genes, suggesting a slow drug metabolism phenotype. This development dates back to the middle of the 20th century, when several different drugs were administered on the ...

  18. The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

    Science.gov (United States)

    Ge, Yanxiu; Ma, Yakun; Li, Lingbing

    2016-10-01

    Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. PMID:27400243

  19. Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

    International Nuclear Information System (INIS)

    The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: →Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. → Histology evidences the intravasation of particles enter the intracellular space. → Non-invasive imaging techniques can display the spatial arrangement of particles. → HPLC-analysis show outstanding drug enrichment in tumors after MDT.

  20. Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Alexiou, Christoph, E-mail: c.alexiou@web.d [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Tietze, Rainer; Schreiber, Eveline [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Jurgons, Roland [Franz Penzoldt Center, University Hospital Erlangen (Germany); Richter, Heike; Trahms, Lutz [PTB Berlin (Germany); Rahn, Helene; Odenbach, Stefan [TU Dresden, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Lyer, Stefan [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany)

    2011-05-15

    The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. Histology evidences the intravasation of particles enter the intracellular space. Non-invasive imaging techniques can display the spatial arrangement of particles. HPLC-analysis show outstanding drug enrichment in tumors after MDT.

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

    OpenAIRE

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

    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 wi...

  2. Clarithromycine-Induced Ventricular Tachycardia in a Geriatric Patient Using Multiple Drugs

    Directory of Open Access Journals (Sweden)

    Gulsah Karaoren

    2014-12-01

    Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.

  3. A Randomized Clinical Trial of Family Therapy in Juvenile Drug Court

    OpenAIRE

    Dakof, Gayle A.; Henderson, Craig E.; Rowe, Cynthia L.; Boustani, Maya; Greenbaum, Paul E.; Wang, Wei; Hawes, Samuel; Linares, Clarisa; Liddle, Howard A.

    2015-01-01

    The objective of this article is to examine the effectiveness of 2 theoretically different treatments delivered in juvenile drug court—family therapy represented by multidimensional family therapy (MDFT) and group-based treatment represented by adolescent group therapy (AGT)—on offending and substance use. Intent-to-treat sample included 112 youth enrolled in juvenile drug court (primarily male [88%], and Hispanic [59%] or African American [35%]), average age 16.1 years, randomly assigned to ...

  4. [Clinical aspects, diagnosis and drug therapy of hyperthyroidism].

    Science.gov (United States)

    Bürgi, U; Gerber, H; Peter, H J

    1995-08-01

    Graves' disease and toxic uni- or multinodular goiter are the most frequent causes of hyperthyroidism. Graves' disease is caused by thyroid stimulating immunoglobulins which are directed against the TSH receptor of thyroid follicular cells. Graves' disease affects more females than males and is associated with diffuse goiter and a rapid appearance of symptoms and signs of hyperthyroidism. Patients with Graves' disease are on average younger than patients with toxic nodular goiter. The diagnosis of Graves' disease is usually easy, particularly if signs of endocrine opthalmopathy are present. Toxic nodular goiter is seen more often in older patients with pre-existing goiters. Symptoms and signs of hyperthyroidism often appear only slowly. Hyperthyroidism in these older patients can be oligosymptomatic. Older patients should therefore be investigated for the presence of hyperthyroidism, even if they present only a few symptoms or signs which could suggest this diagnosis. The development of ultrasensitive TSH assays has simplified the diagnosis of hyperthyroidism and made the TRH-test, often used in the past, almost superfluous. At the present time, it is practically always possible to differentiate between Graves' disease and toxic nodular goiter as the cause of hyperthyroidism on the basis of clinical and laboratory findings alone, and in many cases thyroid scintiscans are therefore no longer necessary. A patient with newly diagnosed Graves' disease is treated with antithyroid drugs (carbimazole or PTU) for one year. If hyperthyroidism persists after this one year of antithyroid drug treatment, or if it recurs, another year of therapy with carbimazole or PTU is indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7545825

  5. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    OpenAIRE

    2011-01-01

    Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.

  6. Laser-induced enhancement of drug cytotoxicity: a new approach to cancer therapy

    Science.gov (United States)

    Flotte, Thomas J.; Anderson, T.; McAuliffe, Daniel J., Sr.; Hasan, Tayyaba; Doukas, Apostolos G.

    1993-07-01

    A new approach to drug delivery has been developed at the Wellman Laboratories of Photomedicine that is analogous to photodynamic therapy except that it utilizes high pressure impulse waves to increase the effectiveness of a variety of drugs rather than light activated drugs. This therapeutic modality offers a generic technology that can be used in a variety of conditions including infections, abscesses, and cancer.

  7. [Gastroesophageal reflux disease: pathophysiology, diagnosis and drug therapy].

    Science.gov (United States)

    Boermeester, M A; van Sandick, J W; van Lanschot, J J; Boeckxstaens, G E; Tytgat, G N; Obertop, H

    1998-06-01

    The principal mechanism leading to gastro-oesophageal reflux is an increased frequency of transient lower oesophageal sphincter relaxations; other factors are oesophageal hypersensitivity to gastric juice, hiatus hernia, and possible duodenal reflux. Patients with classical symptoms such as heartburn and regurgitation may be treated pharmaceutically combined with life style counselling. If the symptoms have not improved after 6 to 12 weeks, endoscopical examination is performed and, if necessary, 24-hour pH monitoring, barium radiographing and manometry. In the case of atypical symptoms such as dysphagia, laryngitis, asthma and chest pain, there is more reason to pursue diagnostic testing. In patients with dysphagia endoscopy is indicated to exclude malignancy. Drug treatment can be subdivided into antacids, H2 receptor antagonists, cytoprotective agents, prokinetics and proton pump inhibitors. In general practice a step-up approach to treatment is preferable, while for specialist treatment a stepdown approach is more (cost-)effective. Drawbacks of medical treatment are considerable frequency of recurrence of oesophagitis, persistence of regurgitation in 'volume refluxers' and controversial data on the possible development of (pre)malignant lesions of oesophagus and stomach. Surgical treatment is a good alternative for patients with persistent severe regurgitation during medical therapy and for young patients who prefer surgery to lifelong medication. Patients with Barrett's oesophagus should undergo regular endoscopic biopsy surveillance. PMID:9752035

  8. [Immunotropic and antihypoxant therapy of experimental drug-sensitive and drug-resistant tuberculosis].

    Science.gov (United States)

    Sukhanov, D S; Vinogradova, T I; Demidik, S N; Zabolotnyh, N V; Vasilieva, S N; Kovalenko, A L; Vitovskaya, M L

    2013-01-01

    The results of pre-clinical research of cycloferon, remaxol and runihol on the model of experimental generalized tuberculosis, caused by the MBT with a different spectrum of drug sensitivity are presented. A considerable increase of the curative effect of the therapy with the used of cycloferon and remaxol. There was manifested the strengthening of lung clearance from the office, reducing the prevalence of specific inflammation in the lungs of the index of lung damage, stimulation of sorption and destructive ability of peritoneal macrophages, inhibited in the course of development of experimental tuberculosis infection. Runihol has no impact on the effectiveness of chemotherapy in the absence of a stimulating influence on the phagocytic function of the peritoneal macrophages. PMID:23805718

  9. 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

  10. Use of intravenous antiarrhythmics to identify concealed Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Brugada Ramon

    2000-08-01

    Full Text Available Abstract Cardiology has recently witnessed the production of an overwhelming amount of data through the advances made in genetics and molecular biology research. Understanding of genetics has tremendous potential to aid in the prevention, diagnosis and treatment of the majority of diseases. Despite the high level of publicity for research discoveries, clinicians have had difficulty in discriminating between what is still basic research and what can be applied to patients. The fact is that we still lack the technology to perform genetic testing in a time frame that is acceptable to clinicians. Meanwhile, then, the only option is to rely on clinical tests that can help us better stratify the individuals at risk for a disease. For example, Brugada syndrome has benefited tremendously from genetics and molecular biology since its initial description in 1992. Genetics will provide a more definitive diagnosis for the disease in the future. For the time being, though, research has shown that the administration of an intravenous class I antiarrhythmic is very useful in identifying patients with a concealed form of the disease.

  11. Proposal for a new therapy for drug-resistant malaria using Plasmodium synthetic lethality inference ☆

    OpenAIRE

    Lee, Sang Joon; Seo, Eunseok; Cho, Yonghyun

    2013-01-01

    Many antimalarial drugs kill malaria parasites, but antimalarial drug resistance (ADR) and toxicity to normal cells limit their usefulness. To solve this problem, we suggest a new therapy for drug-resistant malaria. The approach consists of data integration and inference through homology analysis of yeast–human–Plasmodium. If one gene of a Plasmodium synthetic lethal (SL) gene pair has a mutation that causes ADR, a drug targeting the other gene of the SL pair might be used as an effective tre...

  12. [Oral drug therapy options in the treatment of erectile dysfunction].

    Science.gov (United States)

    Hrgović, Z; Hrgović, I; Thaci, D

    1998-01-01

    The erectile disfunction (ED) represent a disease where diagnostic and therapy are maial standardized. However in the pharmacological there exists a lot of administer justice and legal-insurent problems because there are to few registered medicines. In respect towards the new revolutionary development in the therapy of erectile disfunction, the injectionary therapy of the corpus cavernous loses it is permanent place. Without questions the modilities of the new oral therapy with sildenafil will replace many patients using the "injectionary therapy", concerving psychogenic, neurogenic and soft disturbance into bloodvint during the erection. Simply, it must be said, that there are no further results in the oral therapy, because of the short time research regarding sildenofil. Therefore it is not know what kind of side effects would resulting inffens of sildenafil. After taking one tablet the effects could be expected after half on hour. According to literature recent success with the new therapy in about 90%. PMID:9769638

  13. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    OpenAIRE

    Warangkana Lohcharoenkal; Liying Wang; Yi Charlie Chen; Yon Rojanasakul

    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 formula...

  14. Compliance with drug therapy in rheumatoid arthritis. A longitudinal European study

    NARCIS (Netherlands)

    Viller, F; Guillemin, F; Briancon, S; Moum, T; Suurmeijer, T; van den Heuvel, W

    2000-01-01

    Objective. To delineate compliance with drug therapy in rheumatoid arthritis parents, determine specific characteristics of compliant and noncompliant patients, and took for changes in compliance over time. Patients and methods. A prospective European cohort study (EURIDISS) recruited 556 patients i

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

    OpenAIRE

    Swatantra Kumar Singh Kushwaha; Saurav Ghoshal; Awani Kumar Rai; Satyawan Singh

    2013-01-01

    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 affec...

  16. Drug Therapy for Behavioral and Psychological Symptoms of Dementia.

    Science.gov (United States)

    Wang, Feng; Feng, Ting-Yi; Yang, Shilin; Preter, Maurice; Zhou, Jiang-Ning; Wang, Xiao-Ping

    2016-01-01

    Dementia, which can be induced by diverse factors, is a clinical syndrome characterized by the decline of cognitive function. Behavioral and psychological symptoms of dementia (BPSD) include depression, agitation, and aggression. Dementia causes a heavy burden on patients and their caregivers. Patients with BPSD should be assessed comprehensively by practitioners and offered appropriate non-pharmacologic and pharmacologic therapy. Nonpharmacologic therapy has been recommended as the basal treatment for BPSD; however, pharmacologic therapy is required under many situations. Medications, including antipsychotic agents, antidepressants, sedative and hypnotic agents, mood stabilizers, cholinesterase inhibitors, and amantadine, are extensively used in clinical practice. We have reviewed the progression of pharmacologic therapy for BPSD. PMID:26644152

  17. Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent

    Institute of Scientific and Technical Information of China (English)

    Zhi-fang YANG; Ci-zhen LI; Wei WANG; Ying-min CHEN; Ying ZHANG; Yuan-mou LIU; Hong-wei WANG

    2011-01-01

    Aim: To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone.Methods: Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells.Results: Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (Vmax) of the fAP by 24.4%, and Na+ current (INa) by 18.0%,while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and Vmax of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca2+ current (ICaL) and the K+ tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and Vmax of the fAP and sAP, and both slowed the automatic heart rate.Conclusion: Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit INa, IcaL, and Ikr currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.

  18. 抗心律失常药物基因组学与女性心血管健康%Antiarrhythmic Pharmacogenomics and Cardiovascular Health in Women

    Institute of Scientific and Technical Information of China (English)

    李翠兰; 胡大一

    2012-01-01

    The article reviews the latest progress related to antiarrhythmic pharmacogenomics and cardiovascular diseases and health for women. It includes: (1) basic concepts; (2) cytochrome P450 polymorphisms and antiarrhythmic drugs; (3 ) polymorphisms coding ion channels and arrhythmias; (4) gender differences of expression for ion channel and transfer subunits; (5) gender differences of ventricular repolarization; (6) gender differences of inherrited and drug-induced long QT syndrome and treatment strategy; (7) selective estrogen receptor modulator raloxifene and QT interval; (8) the additive effects of naringenin and antiarrhythmic drug.%本文将从与女性心血管健康相关的角度,综述与心律失常相关的药物基因组学进展.主要内容包括:(1)药物基因组学的概念与研究范围;(2)细胞色素P450遗传多态对抗心律失常药物疗效的影响;(3)编码离子通道的基因多态与心律失常的关系;(4)离子通道及转运亚单位心脏表达的性别差异;(5)心室复极的性别差异及其成因;(6)先天性和药物引起的长QT综合征的性别差异及围产期长QT综合征患者的治疗策略;(7)女性雌激素治疗对QT间期的作用;(8)柚皮素与抗心律失常药物的叠加作用等.

  19. 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…

  20. Optical properties of the chemotherapy drugs used in the central nervous system lymphoma therapy: monitoring drug delivery

    Science.gov (United States)

    Myllylä, T.; Popov, A.; Surazyński, L.; Oinas, J.; Bibikova, O.; Bykov, A.; Wróbel, M. S.; Gnyba, M.; Jedrzejewska-Szczerska, M.; Meglinski, I.; Kuittinen, O.

    2015-07-01

    Our aim is to optically monitor the delivery of the chemotherapy drugs for brain tumours, particularly used in the central nervous system (CNS) lymphoma therapy. In vivo monitoring would help to optimize the treatment and avoiding unnecessary medications. Moreover, it would be beneficial to be able to measure which of the multi-regimen drugs actually do penetrate and how well into the brain tissue. There exist several potential optical measurement techniques to be utilised for the purpose. The most desired method would allow the detection of the drugs without using optical biomarkers as a contrast agent. In this case, for non-invasive sensing of the drug in the brain cortex, the drug should have a reasonably strong optical absorption band somewhere in the range between 600 nm and 1700 nm, and not directly coincident with the strong bands of haemoglobin or water. Alternatively, mid-infrared (MIR) range has the potential for invasive drug monitoring techniques. In this paper, we report the optical properties of several chemotherapy drugs used in CNS lymphoma therapy, such as rituximabi, cyclophosphamide and etoposide. We measured their transmittance and reflectance spectra in near-infrared (NIR) range, particularly 900 nm - 2500 nm, to be considered when choosing the in vivo monitoring method to be developed. The absorption and scattering coefficients were retrieved from the measurements and applying Beer's law. For the measurement of the sum of total transmission and reflection in NIR range we used integrating sphere with spektralo to enable calculation of the scattering coefficient.

  1. 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…

  2. Drug delivery interfaces: A way to optimize inhalation therapy in spontaneously breathing children.

    Science.gov (United States)

    Ari, Arzu

    2016-08-01

    There are several different types of drug delivery interfaces available on the market. Using the right interface for aerosol drug delivery to children is essential for effective inhalation therapy. However, clinicians usually focus on selecting the right drug-device combination and often overlook the importance of interface selection that lead to suboptimal drug delivery and therapeutic response in neonates and pediatrics. Therefore, it is necessary to critically assess each interface and understand its advantage and disadvantages in aerosol drug delivery to this patient population. The purpose of this paper is to provide a critical assessment of drug delivery interfaces used for the treatment of children with pulmonary diseases by emphasizing advantages and problems associated with their use during inhalation therapy. PMID:27610343

  3. Drug therapy and cognitive stimulation in patients with poststroke cognitive impairments

    OpenAIRE

    D. R. Khasanova; Yu V Zhitkova; L.M. Yu.V.

    2014-01-01

    Objective: to compare a multimodal drug approach to treating poststroke cognitive impairments (CI).Patients and methods. Eighty patients with postroke CI in the early recovery period were examined. They were allocated to 4 groups:1) secondary stroke prevention only (a comparison nontreatment group); 2) actovegin infusions; 3) cerebrolysin infusions; 4) drug therapy in combination with non-drug cognitive training using the standard procedure. Follow-ups and neuropsychological assessments were ...

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

    OpenAIRE

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

    2011-01-01

    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-deoxycy...

  5. ANTIMALARIAL DRUGS IN THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS: PAST, PRESENT, FUTURE

    OpenAIRE

    Tatyana Andreyevna Lisitsyna; N. M. Kosheleva

    2010-01-01

    The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil) versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed

  6. ANTIMALARIAL DRUGS IN THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS: PAST, PRESENT, FUTURE

    Directory of Open Access Journals (Sweden)

    Tatyana Andreyevna Lisitsyna

    2010-01-01

    Full Text Available The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed

  7. [Psoriatic arthritis : Overview of drug therapy options and administration characteristics].

    Science.gov (United States)

    Behrens, F; Thaçi, D; Wollenhaupt, J; Krüger, K

    2016-06-01

    Psoriatic arthritis is a chronic inflammatory disease of the musculoskeletal system with association to skin psoriasis and is characterized by variable clinical symptoms with very heterogeneous degrees of disease suffering for patients. Clinical manifestations essentially include alterations to the skin and nails, peripheral arthritis, enthesitis, dactylitis and/or spinal involvement. This variability necessitates an individualized therapy of patients with different therapy targets. Apart from international guidelines no therapy recommendations are available in Germany for treatment of psoriatic arthritis. For this reason this article summarizes the established points, characteristics and aspects to be considered in the therapy of psoriatic arthritis in Germany, taking the various main forms of the disease into consideration. PMID:27259913

  8. A drug-specific nanocarrier design for efficient anticancer therapy

    Science.gov (United States)

    Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao

    2015-07-01

    The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.

  9. A review of over-the-counter drug therapy.

    Science.gov (United States)

    Esmay, J B; Wertheimer, A I

    1979-01-01

    The authors review the extent of the use of nonprescription drugs as well as possible variables influencing such consumption. Various studies indicate that age, sex, personality characteristics, perceptions of health status, socioeconomic factors, parental example, and pharmacists all play parts in determining over-the-counter (OTC) drug utilization. Several sources express concern about the inaccessibility of accurate OTC drug information to the consumer. Indeed, even the FDA has occasional difficulty obtaining reliable facts on both the numbers and formulae of such products. Several studies indicate that consumers acquire information about their home remedies through advertising, friends and relatives, physicians, pharmacists, and product labels. By far the most influential of these is advertising, and much concern has been voiced over consumers' unquestioning faith in drug ads. Examples are cited of deceptive, inaccurate, and unfair advertising practices used by some OTC drug manufacturers. The pros and cons of the "drug-oriented society" theory are discussed, including an analysis of its underlying origins. Testing of the safety and efficacy of nonrescription remedies has proved to be controversial, especially when considering the ramifications of the placebo effect. Different surveys report widespread misuse of OTC's by consumers through overuse, taking several drugs concurrently, and using home remedies to treat potentially serious diseases. PMID:500849

  10. Clinical and Molecular Methods in Drug Development: Neoadjuvant Systemic Therapy in Breast Cancer as a Model.

    Science.gov (United States)

    Braga, Sofia

    2016-01-01

    Neoadjuvant chemotherapy (NACT), neoadjuvant endocrine therapy (NAET), and neoadjuvant targeted therapy (NATT), more recently, have been adopted worldwide as standard of care in locally advanced and inoperable BC. These modalities, collectively called neoadjuvant systemic therapy (NAST), are also used for organ preservation and for mechanistic biological studies on drug response and resistance, drug development, and clinical trials. Furthermore, the response to NACT is a valuable indicator of long-term survival. In this work, the advantages and pitfalls of using NAST in BC for studying drug response and resistance for drug development and clinical trials are discussed as well as practical points on how to set up a NAST clinical trial in BC. PMID:26910079

  11. Neonatal Drug Therapy: The First Frontier of Therapeutics for Children

    OpenAIRE

    K Allegaert; Van den Anker, J

    2015-01-01

    Knowledge about the safe and effective use of medicines in neonates has increased substantially but has resulted in few label changes. Drugs developed for use in adults are reshaped and tailored to specific neonatal indications. However, the use of drugs in neonates should not only mirror adult pharmacotherapy, but should be driven by their own specific needs. Therefore, building collaborative networks may assist to develop a newborn-driven research agenda addressing their clinical needs and ...

  12. Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?

    Directory of Open Access Journals (Sweden)

    Barbetakis Nikolaos

    2004-06-01

    Full Text Available Abstract Background Supraventricular arrhythmias after thoracotomy for pulmonary resections are well documented. There has been considerable interest in their incidence, nature, predictability from preoperative assessment and treatment. The purpose of this study is to define prevalence, type, risk factors for post-thoracotomy supraventricular arrhythmias and to assess the efficacy of amiodarone as an antiarrhythmic drug. Methods The records of 250 patients undergoing pulmonary resection for lung cancer during last two years were followed up in this prospective study with particular attention to possible risk factors (gender, age, extent and side of resection, diabetes mellitus, hypertension, tobacco smoking, beta-blocker ingestion. Patients underwent biopsy only were excluded. Once onset of supraventricular arrhythmia was monitored or documented in the electrocardiogram, intravenous infusion of amiodarone was started with a loading dose of 5 mg/kg in 30 minutes and a maintenance dose of 15 mg/kg until remission of it. Results Forty-three episodes (21.6% of supraventricular arrhythmias were documented with atrial fibrillation being the most common (88.3%. Rhythm disturbances were most likely to develop on the second postoperative day. Pneumonectomy, lobectomy and age >65 years were the statistically significant factors. The overall postoperative mortality was 3.2% and 2.3% for the patients with postoperative supraventricular arrhythmias. In none of the cases did supraventricular arrhythmia cause cardiac failure leading to death. Sinus rhythm was achieved with amiodarone in 37 out of 43 patients (86%. Electrical cardioversion was necessary for 6 patients who were hemodynamically unstable. The most common amiodarone-related complication was bradycardia (13.5%. Conclusions Postoperative supraventricular arrhythmias are a common complication in elderly patients undergoing lung resection surgery (especially pneumonectomy or lobectomy. Amiodarone is

  13. Drug: D08421 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08421 Drug Procainamide (INN) C13H21N3O 235.1685 235.3253 D08421.gif Antiarrhythmi... CLASS I AND III C01BA Antiarrhythmics, class Ia C01BA02 Procainamide D08421 Procainamide (INN) USP drug cla...ssification [BR:br08302] Cardiovascular Agents Antiarrhythmics Procainamide D08421 Procainamide (INN) Target...a, NaV1.x voltage-gated sodium channel (SCN1A) [HSA:6323] [KO:K04833] Procainamid...e [ATC:C01BA02] D08421 Procainamide (INN) voltage-gated sodium channel (SCN2A) [HSA:6326] [KO:K04834] Procai

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

    Science.gov (United States)

    Ultsch, Alfred

    2016-01-01

    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. PMID:27069773

  15. Drug Information Services Today: Current Role and Future Perspectives in Rational Drug Therapy.

    Science.gov (United States)

    Amundstuen Reppe, Linda; Spigset, Olav; Schjøtt, Jan

    2016-02-01

    Polypharmacy and complex drug treatment regimens are becoming increasingly common, which may lead to adverse drug reactions, drug interactions, medication nonadherence, and increasing costs and thus challenge the rational use of drugs. At the same time, the accessibility of drug information increases, and health care professionals may have limited opportunities and capabilities to search and critically evaluate drug information. Clinicians have reported difficulties in searching the best evidence and translating study findings into clinically meaningful information applicable to specific patients. Consequently, it remains a challenge to ensure the rational use of drugs in the years to come. Drug information centers (DICs) have been established to promote the rational use of drugs. One of the most important tasks of DICs is the question and answer services for health care professionals posing drug-related questions. DICs staffed by pharmacists and clinical pharmacologists hold expertise in searching for drug information and critical evaluation of the literature. The uniqueness in this service lies not only in the identification and interpretation of the scientific literature but also in the adaptation of the findings into specific clinical situations and the discussion of possible solutions with the enquirer. Thus, DICs could provide valuable decision support to the clinic. Taking into account the increasing number of possible drug-related questions that will arise today and in the future, the DICs will remain highly relevant in the years to come. However, the DICs must follow the developments in health information technology to disseminate relevant, unbiased drug information to old and new users of the service. Moreover, the DICs are important tools to counterbalance the drug information published by the pharmaceutical industry. PMID:26831829

  16. Obsessive Compulsive Disorder: Improving prognosis through therapy and drug treatment

    OpenAIRE

    Goli, Veeraindar; Krishnan, Ranga; Ellinwood, Everett

    1991-01-01

    An estimated three to seven million Americans suffer from obsessive compulsive disorder at some time in their lives. Until recently, obsessive compulsive disorder was considered refractory to most treatments. However, recent studies indicate a better prognosis with behavioral therapy, antidepressant medications, or both. Behavioral treatment is generally more effective for compulsions than for obsessions.

  17. Blood pressure control, drug therapy, and kidney disease.

    Science.gov (United States)

    Contreras, Gabriel; Greene, Tom; Agodoa, Lawrence Y; Cheek, DeAnna; Junco, George; Dowie, Donna; Lash, James; Lipkowitz, Michael; Miller, Edgar R; Ojo, Akinlou; Sika, Mohammed; Wilkening, Beth; Toto, Robert D

    2005-07-01

    The African American Study of Kidney Disease and Hypertension examined the effect on renal function decline of 2 blood pressure (BP) goals (low mean arterial pressure [MAP] disease (ESRD), death, or GFR decline by 50% or 25 mL/min per 1.73 m2. This report examines the effect of the BP intervention separately in the 3 drug groups. The BP effect was similar among the drug groups for either GFR slope or the main clinical composite. However, the BP effect differed significantly among the drug groups for the composite of ESRD or death (P=0.035) and ESRD alone (P=0.021). Higher event rates for amlodipine patients assigned to the usual BP goal (0.087 per patient-year for ESRD or death and 0.064 per patient-year for ESRD) were seen compared with the remaining groups of the factorial design (range, 0.041 to 0.050 for ESRD or death; and range, 0.027 to 0.036 for ESRD). The low BP goal was associated with reduced risk of ESRD or death (risk reduction 51%; 95% confidence interval, 13% to 73%) and ESRD (54%; 8% to 77%) for amlodipine patients, but not for patients assigned to the other drug groups. These secondary analyses suggest a benefit of the low BP goal among patients assigned to amlodipine, but they must be interpreted cautiously. PMID:15897360

  18. 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...

  19. 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

    2015-06-01

    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. PMID:25918446

  20. Patient compliance with drug therapy for postmenopausal osteoporosis

    International Nuclear Information System (INIS)

    To determine compliance and factors affecting compliance to antiresorptive drugs in osteoporosis, and to compare compliant and non compliant groups in a tertiary care setting. A total of 800 patients with postmenopausal osteoporosis were included in the study. The demographic and reproductive characteristics of all the patients were recorded. Type of antiresorptive drugs prescribed, degree of compliance, time and reasons for discontinuation were studied and analyzed. The mean age of the patients was 64 (+-9) years and their mean duration of follow-up 18 (+-5) months. The prevalence of risk factors for osteoporosis were evenly distributed among treatment groups; 73% patients had a co-morbidity besides osteoporosis while 27% were osteoporotic alone. One or more previous vertebral fractures due to osteoporosis was reported by 14.5% of patients, whereas 35.5% had at least one non-vertebral fracture in their medical history. Out of the total patients 21.5% discontinued the prescribed drug before attending the bone mass re-evaluations, more than half of these within first six months of starting the drugs. The medication that was most frequently discontinued within one year was calcium and vitamin-D (33.7%, p<0.01) while the least discontinued medication was Alendronate (5.9%, p < 0.01) which is taken once a week. In this study the most important determinant of compliance was the type of drug prescribed and its dose frequency, with a definite preference for Alendronate once a week. Treatment compliance was particularly poor for calcium and vitamin-D regimen, thereby emphasizing the need to find new ways of administering supplements, particularly for vitamin-D. (author)

  1. 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.

  2. 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)

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

    OpenAIRE

    Sinuhe eHahn

    2015-01-01

    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...

  4. Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

    OpenAIRE

    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 c...

  5. De-stiffening drug therapy and blood pressure control

    OpenAIRE

    Safar, Michel E.

    2010-01-01

    Michel E SafarParis-Descartes University, Faculty of Medicine, Hôtel-Dieu Hospital, AP-HP, Diagnosis Center, Paris, FranceAbstract: In hypertensive subjects, cardiovascular risk reduction is critically related to the decrease of systolic blood pressure (SBP). De-stiffening therapy means that, in a controlled therapeutic trial of long duration, a selective reduction of SBP has been obtained in the studied group by comparison with the control group, and that this SBP reduction is due ...

  6. Dynamics of an HBV Model with Drug Resistance Under Intermittent Antiviral Therapy

    Science.gov (United States)

    Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan

    2015-06-01

    This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.

  7. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    Science.gov (United States)

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems. PMID:26898739

  8. From hybrid compounds to targeted drug delivery in antimalarial therapy.

    Science.gov (United States)

    Oliveira, Rudi; Miranda, Daniela; Magalhães, Joana; Capela, Rita; Perry, Maria J; O'Neill, Paul M; Moreira, Rui; Lopes, Francisca

    2015-08-15

    The discovery of new drugs to treat malaria is a continuous effort for medicinal chemists due to the emergence and spread of resistant strains of Plasmodium falciparum to nearly all used antimalarials. The rapid adaptation of the malaria parasite remains a major limitation to disease control. Development of hybrid antimalarial agents has been actively pursued as a promising strategy to overcome the emergence of resistant parasite strains. This review presents the journey that started with simple combinations of two active moieties into one chemical entity and progressed into a delivery/targeted system based on major antimalarial classes of drugs. The rationale for providing different mechanisms of action against a single or additional targets involved in the multiple stages of the parasite's life-cycle is highlighted. Finally, a perspective for this polypharmacologic approach is presented. PMID:25913864

  9. Alcohol use and incarceration adversely affect HIV-1 RNA suppression among injection drug users starting antiretroviral therapy

    OpenAIRE

    Palepu, Anita; Tyndall, Mark W.; Li, Kathy; Yip, Benita; O’Shaughnessy, Michael V.; Schechter, Martin T.; Montaner, Julio S.G.; Hogg, Robert S.

    2003-01-01

    We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment ...

  10. The Knowledge Level of Hypertension Patients for Drug Therapy in the Primary Health Care of Malang

    OpenAIRE

    Hananditia R. Pramestutie; Nina Silviana

    2016-01-01

    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 observati...

  11. Pain Relieve after Impacted Wisdom Teeth Extraction Dependent on the Drug Therapy

    OpenAIRE

    Selimović, Edin; Ibrahimagić-Šeper, Lejla; Petričević, Nikola; Nola-Fuchs, Petra

    2011-01-01

    Purpose of this study was to compare the effects of combined therapy using nonsteroid anti-inflammatory analgetics and corticosteroids, and the effects of the mono-therapy with same drugs for post-operative pain after surgical removal of the impacted mandibular third molar. The study was completed at the Department of Oral Surgery and at the Department of Dental Medicine of the Public Institute Health Center Zenica in Zenica. The research included 60 patients divided into 3 groups...

  12. Acute Migraine Therapy: New Drugs and New Approaches

    OpenAIRE

    Monteith, Teshamae S.; Goadsby, Peter J.

    2010-01-01

    Opinion Statement The conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT1B/1D receptor agonists. The ergots, consisting of ergotamine and dihydroergo...

  13. Drug therapy and cognitive stimulation in patients with poststroke cognitive impairments

    Directory of Open Access Journals (Sweden)

    D.R. Khasanova

    2014-10-01

    Full Text Available Objective: to compare a multimodal drug approach to treating poststroke cognitive impairments (CI.Patients and methods. Eighty patients with postroke CI in the early recovery period were examined. They were allocated to 4 groups:1 secondary stroke prevention only (a comparison nontreatment group; 2 actovegin infusions; 3 cerebrolysin infusions; 4 drug therapy in combination with non-drug cognitive training using the standard procedure. Follow-ups and neuropsychological assessments were made at the inclusion in the study and 3 and 6 months after stroke. The state of cognitive functions 6 months after stroke was considered to be an endpoint of the study.Results and discussion. At the inclusion in the study, the mini-mental state examination and the frontal lobe dysfunction scale showed no statistical differences in cognitive functions in different patient groups. At a 3-month follow-up, the cognitive status in the neuronal plasticity stimulation groups was significantly better than in the comparison group (p≤0.05. At a 6-month follow-up, there was a significant cognitive improvement in the combined stimulation group versus the drug-therapy and comparison groups (p≤0.05. Day-to-day activities and independent functioning also improved significantly more promptly in the patients receiving drug or combined therapies. More complex instrumental activities of daily living recovered significantly better during combined cognitive function stimulation than during pharmacological stimulation only. There was evidence that the drugs with proven stimulating effects on neuronal plasticity and nondrug cognitive training were effective in treating CI in the early recovery period of stroke. The combined drug and nondrug poststroke CI treatments reflecting the multimodal approach versus drug therapy were found to be most effective in these patients.

  14. Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

    OpenAIRE

    Gjini, Erida; Brito, Patricia H.

    2016-01-01

    Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. W...

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

    OpenAIRE

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

    2016-01-01

    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...

  16. Use of drug therapy to manage acute cutaneous necrosis of the skin.

    Science.gov (United States)

    Wallace, Jill S; Hall, John C

    2010-04-01

    Acute cutaneous necrosis is defined as a sudden onset of gangrenous skin changes in the skin, associated with significant morbidity and mortality. The following diseases are included in this discussion: coumadin necrosis, heparin necrosis, brown recluse spider bite, necrotizing fasciitis, vasculitis, pyoderma gangrenosum, calciphylaxis, clotting abnormalities and embolic phenomena. The importance of early diagnosis, early distinction and early drug therapy or drug withdrawal must match the diagnosis for maximal preservation of the skin and underlying tissue. PMID:20514791

  17. Variation in Antiarrhythmic Management of Infants Hospitalized with Supraventricular Tachycardia: A Multi-Institutional Analysis.

    Science.gov (United States)

    Guerrier, Karine; Shamszad, Pirouz; Czosek, Richard J; Spar, David S; Knilans, Timothy K; Anderson, Jeffrey B

    2016-06-01

    Supraventricular tachycardia (SVT) is the most frequent form of symptomatic tachyarrhythmia in infants. The purposes of this study were to describe practice patterns of the management of infants hospitalized with SVT and factors associated with 30-day hospital readmission. This was a multi-institutional, retrospective review of the pediatric health information system database of SVT hospitalizations from 2003 to 2013. High-volume centers (HVC) were defined as those at the upper quartile of admissions. Infants with an ICD-9 code of paroxysmal SVT were included. Antiarrhythmics investigated included amiodarone, atenolol, digoxin, esmolol, flecainide, procainamide, propafenone, propranolol, and sotalol. Frequency of antiarrhythmic use based on center volume was the primary end point. Rate of 30-day SVT readmission was the secondary end point. Analysis of factors associated with readmission was assessed by Chi-square analysis and expressed as odds ratio and 95 % confidence interval. A total of 851 patients (60 % male, 44 % neonates) were hospitalized at 43 hospitals. Propranolol, digoxin, and amiodarone were the most frequently utilized antiarrhythmics. HVCs represented 12 hospitals comprising 494 (58 %) patients. Although HVCs were more likely to utilize propranolol (OR 2.5, CI 1.5-4.1), there was no significant difference in the 30-day readmission rate between patients treated at HVCs versus non-HVCs (p = 0.9). The majority of infants with SVT are treated with a small number of antiarrhythmic medications during index hospitalization. Although hospital-to-hospital variation in antiarrhythmic choice exists, there appears to be no difference in readmission. The remaining practice variation may be related to intrinsic patient characteristics. PMID:27033244

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

    Directory of Open Access Journals (Sweden)

    Haeseung Lee

    Full Text Available 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 is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity.

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

    Science.gov (United States)

    Lee, Haeseung; Kang, Seungmin; Kim, Wankyu

    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 is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity. PMID:26954019

  20. 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

  1. Current therapies and technological advances in aqueous aerosol drug delivery.

    Science.gov (United States)

    Watts, Alan B; McConville, Jason T; Williams, Robert O

    2008-09-01

    Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods. PMID:18663654

  2. Molecularly targeted therapy for advanced hepatocellularcarcinoma - a drug development crisis?

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    This review summarizes the current status of neoadjuvantradiation approaches in the treatment of pancreatic cancer,including a description of modern radiation techniques,and an overview on the literature regarding neoadjuvantradio- or radiochemotherapeutic strategies both forresectable and irresectable pancreatic cancer. Neoadjuvantchemoradiation for locally-advanced, primarily non- orborderline resectable pancreas cancer results in secondaryresectability in a substantial proportion of patients withconsecutively markedly improved overall prognosisand should be considered as possible alternative inpretreatment multidisciplinary evaluations. In resectablepancreatic cancer, outstanding results in terms ofresponse, local control and overall survival have beenobserved with neoadjuvant radio- or radiochemotherapy inseveral phase Ⅰ/Ⅱ trials, which justify further evaluationof this strategy. Further investigation of neoadjuvantchemoradiation strategies should be performed preferentiallyin randomized trials in order to improvecomparability of the current results with other treatmentmodalities. This should include the evaluation of optimalsequencing with newer and more potent systemicinduction therapy approaches. Advances in patientselection based on new molecular markers might be ofcrucial interest in this context. Finally modern externalbeam radiation techniques (intensity-modulated radiationtherapy, image-guided radiation therapy and stereotacticbody radiation therapy), new radiation qualities (protons,heavy ions) or combinations with alternative boostingtechniques widen the therapeutic window and contributeto the reduction of toxicity.

  3. 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.

  4. 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. PMID:25767802

  5. 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. PMID:25767802

  6. 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

  7. 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

  8. 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

  9. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Drug utilization management, quality assurance, and... management, quality assurance, and medication therapy management programs (MTMPs). (a) General rule. Each... utilization management program, quality assurance measures and systems, and an MTMP as described in...

  10. A New Caring Model Reduces Need for Drug Therapy for Intellectually Handicapped Persons.

    Science.gov (United States)

    Horten, Irma

    1982-01-01

    Survey results showed a reduction of 22.3 percent in the use of major and minor tranquillizers, indicating that a change in the emphasis of care toward training and a less institutionalized environment may help to reduce the need for drug therapy to control deviant behavior in intellectually handicapped people. (Author/SW)

  11. 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

    2016-01-01

    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. PMID:27229857

  12. 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...

  13. Analysis of Group Process in Marathon Group Therapy with Users of Illicit Drugs.

    Science.gov (United States)

    Page, Richard C; And Others

    1989-01-01

    Used Hill Interaction Matrix to measure content and quality of interactions in 12-hour therapy group of 12 male drug addicts and 3 therapists. Categories of therapeutic work included conventional, assertive, speculative, and confrontive; categories of content included topic, group, personal, and relationship. Group was highly confrontive; most…

  14. 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.

  15. 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.

  16. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance

    Science.gov (United States)

    Boehm, Thomas; Folkman, Judah; Browder, Timothy; O'Reilly, Michael S.

    1997-11-01

    Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells. In contrast, endothelial cells are genetically stable, homogenous and have a low mutational rate. Therefore, antiangiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance. Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor. An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.

  17. Spatiotemporally synchronized cancer combination therapy using photo-activated nanoparticle drug delivery systems (Conference Presentation)

    Science.gov (United States)

    Hasan, Tayyaba

    2016-03-01

    This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.

  18. 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. PMID:27249674

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Current and novel drug therapies for idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Adamali HI

    2012-09-01

    Full Text Available Huzaifa I Adamali,1 Toby M Maher1–31Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; 2National Heart and Lung Institute, Imperial College London, London, UK; 3Centre for Respiratory Research, University College London, London, UKAbstract: Over the past decade, there has been a cohesive effort from patients, physicians, clinical and basic scientists, and the pharmaceutical industry to find definitive treatments for idiopathic pulmonary fibrosis (IPF. As understanding of disease behavior and pathogenesis has improved, the aims of those treating IPF have shifted from reversing the disease to slowing or preventing progression of this chronic fibrotic illness. It is to be hoped that by slowing disease progression, survival will be improved from the current dismal median of 3.5 years following diagnosis. In Europe and Asia, a milestone has recently been reached with the licensing of the first IPF-specific drug, pirfenidone. This review assesses the current treatment modalities available for IPF, including pirfenidone. It also turns an eye to the future and discusses the growing number of promising compounds currently in development that it is hoped, in time, will make their way into the clinic as treatments for IPF.Keywords: interstitial lung disease, pirfenidone, clinical trials, usual interstitial pneumonia, acute exacerbations

  1. [Drug treatment and interventional pain therapy in back pain patients].

    Science.gov (United States)

    Sprott, Haiko; Klauke, Wolfgang

    2013-09-01

    The treatment of chronic, non-malignant low-back pain is based on the patients' history and the clinical examination. It can be assumed that half of the cases present with a neuropathic pain component which needs to be treated with antidepressive and antiepileptic drugs instead of "pure" analgesics. Opioids should be considered with extreme caution because of their toxicity. Chronic non-malignant back pain is the prototype for interdisciplinary treatment approaches and multi-modal interdisciplinary settings, including pain programmes. However, a personalised strategy has to be preferred in most cases. A quick relief of pain is important in order to improve function as well as to re-integrate the patient into professional life. Spinal infiltrations can be of both diagnostic as well as therapeutic benefits. Their indication must be considered carefully, especially if the invasive diagnostic intervention has no therapeutic consequences. The interventional procedures should only be used as part of a multimodal approach in patients without any psychological problem. The sole use of interventions supports the purely somatic orientation of many patients and thus leads us in the wrong direction. PMID:23985154

  2. Drug: D03367 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03367 Drug Capobenate sodium (USAN) C16H22NO6. Na 347.1345 347.3387 D03367.gif Car...diac depressant [anti-arrhythmic] CAS: 27276-25-1 PubChem: 17397516 LigandBox: D03367 NIKKAJI: J21.180J ATOM

  3. ANTIEPILEPTIC DRUG THERAPY AND SERUM CARNITINE LEVELS IN CHILDREN PRIOR TO AND FOLLOWING TREATMENT

    Directory of Open Access Journals (Sweden)

    N. SHEIKH

    2006-06-01

    Full Text Available Background:The physiologic function of carnitine, oxidation of fatty acid and lipidmetabolism, is severely affected in carnitine deficiency, secondaryforms of which lead to renal tubular disorders and chronic renalfailure. Reduction in serum carnitine has been frequently reportedin patients and experimental animals treated with antiepileptic drugs,one of which, valproic acid has consistently been found to cause thedeficiency; the antiepileptic drugs, valproic acid, has consistentlybeen found to cause the deficiency. Previous results, however, regardingthe effects of other antiepileptic drugs have been less consistent.Considering the controversial results available in lterarure, the aim ofthis study was to determine the effect of Valproic acid, Carbamazepineand Phenobarbital on serum carnitine levels in epileptic children.Methods:In the present study, serum carnitine levels were randomly monitoredbefore and six months after therapy in 39 epileptic patients receivingthe antiepileptic drugs mentioned. Patient blood samples were takenbefore and six months after treatment and L-carnitine level wasdetermined using the UV enzymatic test (Rouche Kit spectronicGenesis 2, 340 nm.Results:Results showed a significant fall in the L-carnitine levels of epilepticchildren taking these drugs (P< 0.01.Conclusion:Considering the reducing effect of antiepileptic drugs on serumcarnitine levels, it is recommended that a carnitine supplement beadministered in pediatric epileptic patients to prevent the deficiencyand related consequences caused by such therapies.

  4. 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

    2015-09-01

    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.

  5. 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

  6. Drug-Encoded Biomarkers for Monitoring Biological Therapies.

    Science.gov (United States)

    Tsoneva, Desislava; Stritzker, Jochen; Bedenk, Kristina; Zhang, Qian; Frentzen, Alexa; Cappello, Joseph; Fischer, Utz; Szalay, Aladar A

    2015-01-01

    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. PMID:26348361

  7. Molecular fundamentals of drug interactions in the therapy of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Regulska

    2014-03-01

    Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

  8. Functional mesoporous silica nanoparticles (MSNs) for highly controllable drug release and synergistic therapy.

    Science.gov (United States)

    Cheng, Yin-Jia; Zeng, Xuan; Cheng, Dong-Bing; Xu, Xiao-Ding; Zhang, Xian-Zheng; Zhuo, Ren-Xi; He, Feng

    2016-09-01

    Synergistic therapy involving two or more therapeutic agents with different anticancer mechanisms represents a promising approach to eradicate chemotherapy-refractory cancers. However, the preparation of a synergistic therapy platform generally involves complicated procedures to encapsulate different therapeutic agents and thereby increases the purification difficulty. In this work, we reported a simple but robust strategy to prepare a highly controllable drug delivery system (DDS) for synergistic cancer therapy. To construct this robust DDS, mesoporous silica nanoparticles (MSNs) were employed as a nanoplatform to encapsulate anticancer drug doxorubicin (DOX). After using a tumor-targeting cellular membrane-penetrating peptide (TCPP) and a mitochondria-targeting therapeutic peptide (TPP) to seal the surface pores via disulfide bonds, these newly developed MSNs can target cancer cells, penetrate cell membrane and rapidly release anticancer drug and mitochondria-targeted peptide in cytoplasm, inducing a remarkable synergistic anticancer effect. The new design concept reported here will promote the development of targeted and smart DDSs for synergistic cancer therapy. PMID:27182657

  9. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension.

    Science.gov (United States)

    Chrysant, Steven G

    2011-11-01

    Hypertension (HTN) affects an estimated 76.4 million US adults. Despite improvements in blood pressure (BP) control rates and the availability of effective antihypertensive agents, only 50% of these individuals achieve BP control. It is now recognized that many patients will require ≥ 2 antihypertensive agents to achieve BP control. Both the current US and reappraisal of the 2007 European guidelines include dual-combination regimens among recommended treatments for initial HTN therapy. For patients requiring 3 drugs, the combination of agents with complementary mechanisms of action (ie, renin-angiotensin-aldosterone system blocker, calcium channel blocker, and diuretic) has been recognized as rational and effective. Three single-pill triple-drug combinations have recently been approved for use in HTN in the United States: valsartan (VAL)/amlodipine (AML)/hydrochlorothiazide (HCTZ); olmesartan medoxomil (OM)/AML/HCTZ; and aliskiren (ALI)/VAL/HCTZ. Triple-combination regimens have resulted in a greater proportion of patients achieving BP control compared with dual-combination regimens, with significantly lower BP levels documented after only 2 weeks at maximum doses. Single-pill combinations offer convenience to address barriers to BP control such as poor adherence to therapy and therapeutic inertia. Additional benefits of combining antihypertensive agents from different classes include improved efficacy, safety, and reduction of cardiovascular risk. In patients with essential HTN for whom dual therapy is inadequate, single-pill triple-drug therapy can offer a simplified and effective treatment strategy. PMID:22104451

  10. Pharmaceutical care interventions, their outcomes and patients’ satisfaction in antiretroviral drug therapy

    Directory of Open Access Journals (Sweden)

    Nwaozuzu, E.E.

    2013-03-01

    Full Text Available Pharmacist’s interventions (also known as pharmaceutical care plans are means of solving the drug therapy problems identified in pharmaceutical care. Outcomes are the results of pharmacists’ intervention activities. Patients’ satisfaction refers to patients’ feeling of fulfillment, pleasure or happiness with the services they have received. This study was designed to determine the types of pharmacist interventions applied in the pharmaceutical care of HIV patients receiving treatment at a tertiary hospital in southeast Nigeria, the types of outcomes of such interventions and level of patients’ satisfaction with their drug therapy. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The results showed significant reductions in the frequency of the various interventions and parameters measured after the interventions. The study concluded that pharmaceutical interventions influences patients’ adherence, optimizes their drug therapy and improves rational prescribing and care resulting in significant improvements in the outcomes of their treatment and levels of satisfaction.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Drug delivery system design and development for boron neutron capture therapy on cancer treatment

    International Nuclear Information System (INIS)

    We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery

  14. Antiarrhythmic or time bomb? A severe iatrogenic bradyarrhythmia

    Directory of Open Access Journals (Sweden)

    S. Matheou

    2013-05-01

    Full Text Available We report a case of severe bradyarrythmia with hypotension and extremely large QRS due to proarrhythmic effect of drug combination (amiodarone following infusion of propafenone for the conversion of Paroxysmal Atrial Fibrillation (PAF in a 74 year old woman. The authors focus on the important side effects and complications due to aggressive treatment of not life-threatening arrhythmias, such as PAF without haemodinamic compromise in older patients. At conclusion “primum non nocere“.

  15. Regional myocardial ajmaline concentration and antiarrhythmic activity for ischaemia- and reperfusion-induced arrhythmias in rats.

    OpenAIRE

    Okumura, K; Hashimoto, Y.; Yasuhara, M; R. Hori

    1988-01-01

    1. Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion-induced arrhythmias were investigated in anaesthetized rats. 2. Ajmaline (2 mg kg-1, i.v.) was effective in suppressing ischaemia-induced arrhythmias whether given pre- or post-occlusion. 3. Ajmaline diminished the reperfusion-induced arrhythmias completely when given pre-occlusion but had little effect when given post-occlusion. 4. Reperfusion-induced increases in pl...

  16. [Anti-arrhythmic properties of GABA and GABA-ergic system activators].

    Science.gov (United States)

    Tiurenkov, I N; Perfilova, V N

    2002-01-01

    Clinical and experimental data available in the literature are summarized, which are indicative of the antiarrhythmogenic properties of GABA and substances possessing GABA-positive activity (phenibut, piracetam, sodium hydroxybutyrate, lithium hydroxybutyrate, etc.). The antiarrhythmic effects are manifested in various cases of the heart rhythm violation. The mechanism of this action is related to activation of the central and peripheral retarding GABAergic system, as well as to antihypoxant, antioxidant, and antistressor effects. PMID:12025796

  17. Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction.

    Science.gov (United States)

    Keller, Frieder; Schröppel, Bernd; Ludwig, Ulla

    2015-07-01

    Patients with cancer have a high inherent risk of infectious complications. In addition, the incidence of acute and chronic kidney dysfunction rises in this population. Anti-infective drugs often require dosing modifications based on an estimate of kidney function, usually the glomerular filtration rate (GFR). However, there is still no preferential GFR formula to be used, and in acute kidney injury there is always a considerable time delay between true kidney function and estimated GFR. In most cases, the anti-infective therapy should start with an immediate and high loading dose. Pharmacokinetic as well as pharmacodynamic principles must be applied for further dose adjustment. Anti-infective drugs with time-dependent action should be given with the target of high trough concentrations (e.g., beta lactam antibiotics, penems, vancomycin, antiviral drugs). Anti-infective drugs with concentration-dependent action should be given with the target of high peak concentrations (e.g., aminoglycosides, daptomycin, colistin, quinolones). Our group created a pharmacokinetic database, called NEPharm, hat serves as a reference to obtain reliable dosing regimens of anti-infective drugs in kidney dysfunction as well as renal replacement therapy. To avoid the risk of either too low or too infrequent peak concentrations, we prefer the eliminated fraction rule for dose adjustment calculations. PMID:26167456

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Cancer therapy improvement with mesoporous silica nanoparticles combining targeting, drug delivery and PDT.

    Science.gov (United States)

    Gary-Bobo, Magali; Hocine, Ouahiba; Brevet, David; Maynadier, Marie; Raehm, Laurence; Richeter, Sébastien; Charasson, Virginie; Loock, Bernard; Morère, Alain; Maillard, Philippe; Garcia, Marcel; Durand, Jean-Olivier

    2012-02-28

    The synthesis of mesoporous silica nanoparticles (MSN) covalently encapsulating fluoresceine or a photosensitizer, functionalized with galactose on the surface is described. Confocal microscopy experiments demonstrated that the uptake of galactose-functionalized MSN by colorectal cancer cells was mediated by galactose receptors leading to the accumulation of the nanoparticles in the endosomal and lysosomal compartments. The MSN functionalized with a photosensitizer and galactose were loaded with the anti-cancer drug camptothecin. Those MSN combining drug delivery and photodynamic therapy were tested on three cancer cell lines and showed a dramatic enhancement of cancer cell death compared to separate treatments. PMID:22178618

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

    Directory of Open Access Journals (Sweden)

    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.

  1. ZnO nanoparticles as drug delivery agent for photodynamic therapy

    International Nuclear Information System (INIS)

    Multidrug resistance (MDR) limits the success of many tumoricidal drugs. Non-significant accumulation of the drug into the target site is one major problem in photodynamic therapy. Nanoparticles are extensively used as efficient drug carriers in various local infectious and premalignant biological tissues. Due to their unique physical and chemical properties, PEGylated zinc oxide nanoparticles (ZnO NPs) exhibit high drug loading capacities, sustained drug release profiles and long-term anticancer efficacy. (Polyethylene glycol) PEG-zinc oxide nanoparticles were synthesized using the aquis chemical technique. Morphology/structural analysis of the said nanoparticles was confirmed by applying many techniques, e.g. scanning electron microscopy (SEM) and XRD. Average grain size of the nanoparticles, which was ≈100 nm, was calculated by applying the Scherrer formula. The PEGylated ZnO NPs were loaded with protoporphyrin IX (PpIX) to enhance the capability of drug carrying potency. Current work focused on the comparison of the cell killing effect (apoptosis/necrosis) by functionalizing different nanostructures via PEGylated ZnO NPs and bare ZnO NPs using the free-standing drug delivery procedure. ZnO NPs were used as anticancer drug vehicles because of their biocompatibility and bio-safety profile. The apoptotic effect of PEGylated tumoricidal drugs has been studied in human muscle carcinoma (RD cell line) in the dark as well as under laser exposure. It was concluded that PpIX localization was a significant time greater using encapsulation as compared to a conventional drug delivery system. This new technique may find excellent opportunities in the field of nanomedicine, especially in a multidrug delivery system. (letter)

  2. ZnO nanoparticles as drug delivery agent for photodynamic therapy

    Science.gov (United States)

    Fakhar-e-Alam, M.; Rahim, S.; Atif, M.; Hammad Aziz, M.; Imran Malick, M.; Zaidi, S. S. Z.; Suleman, R.; Majid, A.

    2014-02-01

    Multidrug resistance (MDR) limits the success of many tumoricidal drugs. Non-significant accumulation of the drug into the target site is one major problem in photodynamic therapy. Nanoparticles are extensively used as efficient drug carriers in various local infectious and premalignant biological tissues. Due to their unique physical and chemical properties, PEGylated zinc oxide nanoparticles (ZnO NPs) exhibit high drug loading capacities, sustained drug release profiles and long-term anticancer efficacy. (Polyethylene glycol) PEG-zinc oxide nanoparticles were synthesized using the aquis chemical technique. Morphology/structural analysis of the said nanoparticles was confirmed by applying many techniques, e.g. scanning electron microscopy (SEM) and XRD. Average grain size of the nanoparticles, which was ≈100 nm, was calculated by applying the Scherrer formula. The PEGylated ZnO NPs were loaded with protoporphyrin IX (PpIX) to enhance the capability of drug carrying potency. Current work focused on the comparison of the cell killing effect (apoptosis/necrosis) by functionalizing different nanostructures via PEGylated ZnO NPs and bare ZnO NPs using the free-standing drug delivery procedure. ZnO NPs were used as anticancer drug vehicles because of their biocompatibility and bio-safety profile. The apoptotic effect of PEGylated tumoricidal drugs has been studied in human muscle carcinoma (RD cell line) in the dark as well as under laser exposure. It was concluded that PpIX localization was a significant time greater using encapsulation as compared to a conventional drug delivery system. This new technique may find excellent opportunities in the field of nanomedicine, especially in a multidrug delivery system.

  3. Efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylor in patients receiving long-term non-steroidal anti-inflammatory drugs treatnent

    Institute of Scientific and Technical Information of China (English)

    黄鑫薪

    2013-01-01

    Objective To explore the efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylori(Hp) in patients receiving long-term non-steroidal antiinflammatorv drugs(NSAID) treatment. Methods Patients receiving long-term NSAID treatment were enrolled

  4. Tuberculosis-advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    Science.gov (United States)

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480 000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  5. Combination Therapy Counteracts the Enhanced Transmission of Drug-Resistant Malaria Parasites to Mosquitoes

    OpenAIRE

    Hallett, Rachel L; Colin J Sutherland; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J.; Pinder, Margaret; Walraven, Gijs; Geoffrey A T Targett; Alloueche, Ali

    2004-01-01

    Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resi...

  6. Drug Therapy Problems In Management Of Hypertensive Outpatients Admitted To Four Indonesian Primary Health Centers

    OpenAIRE

    Nasution, Azizah; Khairunnisa; Tanjung, Hari Ronaldo

    2016-01-01

    Objective: This study aimed to evaluate the antihypertensive utilization and drug therapy problems (DTPs) in the treatment of patients with hypertension. Methods: This prospective analytical study used a self-determined questionnaire to collect 2-month period data of hypertensive patients (n=107) admitted to four primary health centers in Medan (Medan Deli, Helvetia, Glugur Darat, and Teladan). Inclusion criteria were patients diagnosed with hypertension, age ≥18 years, and under ...

  7. Electromotive drug administration for treatment of therapy-refractory overactive bladder

    OpenAIRE

    A. Gauruder Burmester; A. Biskupskie; A. Rosahl; R. Tunn

    2008-01-01

    PURPOSE: Evaluate the benefits of electromotive drug administration (EMDA) as an alternative technique in patients with chronic overactive bladder in terms of improvement of symptoms, quality of life, and sexuality. MATERIAL AND METHODS: A total of 72 patients with therapy-refractory overactive bladder according to the ICS (International Continence Society) definition, were treated by EMDA. The regimen consisted of three treatment cycles, each with 3 instillations at 2-week intervals. The sol...

  8. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

    OpenAIRE

    Giovana Maria Fioramonti Calixto; Jéssica Bernegossi; Laura Marise de Freitas; Carla Raquel Fontana; Marlus Chorilli

    2016-01-01

    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 deliver...

  9. Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

    OpenAIRE

    Anish Babu; Templeton, Amanda K.; Anupama Munshi; Rajagopal Ramesh

    2013-01-01

    The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH) guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ...

  10. Designing anti-cancer drugs and directing anti-cancer therapy

    OpenAIRE

    Velasquez, Elinor; Soto-Andrade, Jorge; Bongalon, Ben

    2014-01-01

    A prototype for a web application was designed and implemented as a guide to be used by clinicians when designing the best drug therapy for a specific cancer patient, given biological data derived from the patients tumor tissue biopsy. A representation of the patients metabolic pathways is displayed as a graph in the application, with nodes as substrates and products and edges as enzymes. The top metabolically active sub- paths in the pathway, ranked using an algorithm based on both the patie...

  11. Implementation of a drug therapy monitoring clinic in a primary-care setting.

    Science.gov (United States)

    Yanchick, J K

    2000-12-15

    The development and implementation of a drug therapy monitoring clinic in the primary-care clinics of a military hospital are described. To improve patient care and decrease costs associated with treating chronic diseases, in August 1995 the pharmacy department established a drug therapy monitoring clinic. The clinic was responsible for initiating and monitoring treatment plans for patients with chronic diseases, implementing clinical guidelines, providing educational programs, collecting and analyzing outcome data, and handling requests for medication extensions. Treatment followed existing national standards and Department of Defense guidelines modified for the institution. The clinic began with one clinical pharmacy specialist, and within a year it added another clinical pharmacist and a technician. The clinic first obtained patients via consultations from providers in primary care; this was soon extended to all departments. In addition, the pharmacist was available to see walk-in patients needing medication extensions. Later, referrals came for inpatients and patients seen in the emergency room for asthma or diabetes mellitus, as well as for inpatients receiving oral anticoagulation therapy. For fiscal year 1999, the clinic saw 104 (+/- 44.3) patients per month seeking medication extensions. It also handled 24,873 clinical interventions that year, resulting in projected annual savings of $1,085,560. Chart review indicated that compliance with national standards improved dramatically for patients with diabetes mellitus or asthma followed by pharmacists compared with physician monitoring during the same period and before the clinic began. The wait time for reviewing laboratory results and for patients receiving anticoagulation therapy was eliminated, and doses were changed immediately, if needed. A comprehensive pharmacist-managed drug therapy monitoring clinic for outpatients with chronic diseases can result in positive patient outcomes and more cost

  12. Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2013-01-01

    Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

  13. Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Caecilia HC Sukowati, Natalia Rosso, Lory S Crocè, Claudio Tiribelli

    2010-03-01

    Full Text Available Hepatocellular carcinoma (HCC is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.

  14. 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. 

  15. Impact of pharmaceutical care interventions on the occurrence and resolution of side/adverse drug effects associated with antiretroviral drug therapy

    Directory of Open Access Journals (Sweden)

    Nwaozuzu, E.E.

    2012-12-01

    Full Text Available Pharmaceutical care (PC has been shown to improve the outcome of drug therapy in many disease conditions. HIV/AIDS is one of the disease conditions that are fraught with many problems that can benefit from this new emphasis of pharmacy practice also known as ‘pharmacists care’. Adverse drug reactions or effects are unintended and undesirable effects of drugs other than their known and expected actions which can be unpleasant and sometimes fatal. This study is designed to evaluate the impact of pharmaceutical care activities on the occurrence of side/adverse drug reactions in HIV/AIDS patients receiving antiretroviral drugs. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care’ was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The study identified about sixty (60 different types of side/adverse effects occurring among these patients through observation and patient complaints. The study also showed significant reduction in the incidence of side/adverse drug effects following the Pharmacist’s intervention activities, p ≥ 0.5. The study showed that pharmacists’ interventions in antiretroviral drug therapy through Pharmaceutical care can significantly reduce the incidence of side/adverse drug effects in HIV/AIDS patients receiving antiretroviral drugs.

  16. Cost-effectiveness of drug therapy for hypercholesterolaemia: a review of the literature.

    Science.gov (United States)

    Thompson, D; Oster, G

    1992-07-01

    In this article we review published studies of the cost-effectiveness of drug therapy for hypercholesterolaemia to take stock of the principal findings that have been reported to date. We identified 9 studies that met all criteria for inclusion in our review, including 3 of bile-acid sequestrants (cholestyramine, colestipol), 2 of HMG-CoA reductase inhibitor (lovastatin), and 4 that considered both an HMG-CoA reductase inhibitor (simvastatin) and a bile-acid sequestrant (cholestyramine). While these studies were largely consistent in methodological approach, some differences were noted in the costs attributed to drug therapy. The cost-effectiveness of therapy with bile-acid sequestrants was found to range from $100 000 to $209 000 per year of life saved (1991 $US) for middle-aged men (42 to 55 years of age) with moderately high cholesterol levels (280 to 290 mg/dl) and otherwise average coronary risk characteristics. Corresponding cost-effectiveness ratios that have been reported for lovastatin range from $64 000 to $82 000, while those for simvastatin range from $45 000 to $65 000. Studies to date therefore suggest that therapy with HMG-CoA reductase inhibitors (i.e. lovastatin and simvastatin) is substantially more cost-effective than treatment with bile-acid sequestrants. PMID:10146977

  17. SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy

    Science.gov (United States)

    Na, Han-Heom; Noh, Hee-Jung; Cheong, Hyang-Min; Kang, Yoonsung; Kim, Keun-Cheol

    2016-01-01

    The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. [BMB Reports 2016; 49(4): 238-243] PMID:26949019

  18. 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

    2016-01-01

    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. PMID:26978341

  19. 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.

  20. Local drug delivery agents as adjuncts to endodontic and periodontal therapy.

    Science.gov (United States)

    Puri, K; Puri, N

    2013-01-01

    In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252

  1. Knee osteoarthritis a pathological basis for use of newer drug therapies

    Directory of Open Access Journals (Sweden)

    Mukundraj S. Keny

    2014-06-01

    Full Text Available Knee osteoarthritis (OA is a disease of the whole knee joint occurring due to an interaction between inflammatory, hypoxic, and mechanical pathways. Initial management includes monotherapy with analgesics or anti and #8209;inflammatory agents, eventually switching over to combination therapy with steroids and/or newer drugs. Cardiovascular risks associated with non and #8209;steroidal anti and #8209;inflammatory drugs (NSAIDs limit their long term use. Hence, novel target receptors or pathways, which remain unaffected by conventional therapy and modify disease are being increasingly looked for. Newer drugs such as glucosamine, chondroitin, methylsulfonylmethane, diacerein along with vitamins/minerals are commonly used as adjuncts to NSAIDs or as monotherapy. Because of their novel mechanisms of action and better safety profile they seem to be promising as disease modifying agents in the treatment of OA. Google, PubMed, Cochrane databases and Science Direct search was performed, and relevant articles were identified. This review focuses on the pathological targets which these drugs modify in order to bring about a symptom modifying effect. [Int J Basic Clin Pharmacol 2014; 3(3.000: 424-430

  2. Drugs used in pediatric intravenous therapy: a study on potentialy interactive combination

    Directory of Open Access Journals (Sweden)

    Tathiana Silva de Souza Martins

    2012-04-01

    Full Text Available The aim of this study was: to identify and classify the main drugs administered by intravenous method in the prescriptions of the pediatric units and to verify the occurrence of potentially medicamentous interactions. It is an exploratory descriptive research, with quantitative treatment of the data. The population was formed by 1,248 pediatric prescriptions and the sample of 205, having as inclusion criteria prescriptions with intravenous therapy of two or more drugs. Data collection was made at the Medical Files of a University Hospital. It was verified that most of the drugs used presented interactive potential; 60% of the sample had been exposed to the co-administration of antimicrobials. The vancomycin was the most present agent, and all the children used an antimicrobial during the institutionalization period. It was concluded that the co-administration of potentially interactive drugs associated to simultaneous scheduling of administration of such agents could predispose the patients to undesired events, affecting, this way, the safety of the therapy.

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

    Science.gov (United States)

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

    2016-03-01

    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. PMID:26725041

  4. Fighting cancer with nanomedicine---drug-polyester nanoconjugates for targeted cancer therapy

    Science.gov (United States)

    Yin, Qian

    The aim of my Ph. D. research is to develop drug-polyester nanoconjugates (NCs) as a novel translational polymeric drug delivery system that can successfully evade non-specific uptake by reticuloendothelial system (RES) and facilitate targeted cancer diagnosis and therapy. By uniquely integrating well-established chemical reaction-controlled ring opening polymerization (ROP) with nanoprecipitation technique, I successfully developed a polymeric NC system based on poly(lactic acid) and poly(O-carboxyanhydrides) (OCA) that allows for the quantitative loading and controlled release of a variety of anticancer drugs. The developed NC system could be easily modified with parmidronate, one of bisphosphonates commonly used as the treatment for disease characterized by osteolysis, to selectively deliver doxorubicin (Doxo) to the bone tissues and substantially to improve their therapeutic efficiency in inhibiting the growth of osteosarcoma in both murine and canine models. More importantly, the developed NCs could avidly bind to human serum albumin, a ubiquitous protein in the blood, to bypass the endothelium barrier and penetrate into tumor tissues more deeply and efficiently. When compared with PEGylated NCs, these albumin-bound NCs showed significantly reduced accumulation in RES and enhanced tumor accumulation, which consequently contributed to higher their tumor inhibition capabilities. In addition, the developed NC system allows easy incorporation of X-ray computed tomography (CT) contrast agents to largely facilitate personalized therapy by improving diagnosis accuracy and monitoring therapeutic efficacy. Through the synthetic and formulation strategy I developed, a large quantity (grams or larger-scale) of drug-polyester NCs can be easily obtained, which can be used as a model drug delivery system for fundamental studies as well as a real drug delivery system for disease treatment in clinical settings.

  5. Hemodynamic effects of the new antiarrhythmic agent restacorin in patients with normal and decreased left ventricular function.

    Science.gov (United States)

    Tuininga, Y S; Crijns, H J; Oosterhuis, B; Wiesfeld, A C; van Wijk, L M; Albronda, F; de Bruin, H; Jonkman, J H; Kozma, C; Lie, K I

    1994-03-01

    The hemodynamic and pharmacokinetic effects of the novel class 1c antiarrhythmic drug restacorin were investigated in two groups of patients. Group I consisted of 5 patients with normal left ventricular (LV) function, and group II consisted of 10 patients with mild heart failure [New York Heart Association (NYHA) II; mean LV ejection fraction 33 +/- 6%]. The study had an open label, baseline-controlled, single-dose design. Restacorin was infused in a total dosage of 1.2 mg/kg. In group I, the only significant change as compared with baseline findings was a 25% increase in right atrial pressure. In group II; cardiac output (CO), dP/dt, and stroke work index (SWI) decreased significantly (-18, -11, and -24%, respectively). In addition, a significant 32% increase was noted in pulmonary artery wedge pressure (PAWP), and a 27% increase occurred in systemic vascular resistance (SVR). No changes were observed in heart rate (HR) or mean arterial blood pressure (MAP). CO and SVR at baseline correlated with the average plasma concentrations (r = -0.65 and p = 0.009 and r = 0.56 and p = 0.028 respectively). Creatinine clearance was inversely correlated to the restacorin plasma concentration (r = -0.51, p = 0.05). The half-life (t1/2) elimination time of restacorin was 2.60 h for group I, and 4.06 h for group II. Clearance was 51.4 and 32.2 L.h-1, respectively. Restacorin appears to be well tolerated in patients with normal LV function. The drug is not recommended for use in patients with reduced LV function because of its moderate negative inotropic effect. PMID:7515984

  6. 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. PMID:26799352

  7. Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy.

    Science.gov (United States)

    Kuo, Chih-Yu; Liu, Ting-Yu; Chan, Tzu-Yi; Tsai, Sung-Chen; Hardiansyah, Andri; Huang, Li-Ying; Yang, Ming-Chien; Lu, Ruey-Hwa; Jiang, Jeng-Kai; Yang, Chih-Yung; Lin, Chi-Hung; Chiu, Wen-Yen

    2016-04-01

    Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy. PMID:26705859

  8. Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection.

    Science.gov (United States)

    Menéndez-Arias, Luis; Alvarez, Mar

    2014-02-01

    One to two million people worldwide are infected with the human immunodeficiency virus type 2 (HIV-2), with highest prevalences in West African countries, but also present in Western Europe, Asia and North America. Compared to HIV-1, HIV-2 infection undergoes a longer asymptomatic phase and progresses to AIDS more slowly. In addition, HIV-2 shows lower transmission rates, probably due to its lower viremia in infected individuals. There is limited experience in the treatment of HIV-2 infection and several antiretroviral drugs used to fight HIV-1 are not effective against HIV-2. Effective drugs against HIV-2 include nucleoside analogue reverse transcriptase (RT) inhibitors (e.g. zidovudine, tenofovir, lamivudine, emtricitabine, abacavir, stavudine and didanosine), protease inhibitors (saquinavir, lopinavir and darunavir), and integrase inhibitors (raltegravir, elvitegravir and dolutegravir). Maraviroc, a CCR5 antagonist blocking coreceptor binding during HIV entry, is active in vitro against CCR5-tropic HIV-2 but more studies are needed to validate its use in therapeutic treatments against HIV-2 infection. HIV-2 strains are naturally resistant to a few antiretroviral drugs developed to suppress HIV-1 propagation such as nonnucleoside RT inhibitors, several protease inhibitors and the fusion inhibitor enfuvirtide. Resistance selection in HIV-2 appears to be faster than in HIV-1. In this scenario, the development of novel drugs specific for HIV-2 is an important priority. In this review, we discuss current anti-HIV-2 therapies and mutational pathways leading to drug resistance. PMID:24345729

  9. 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.

  10. Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2012-04-01

    Full Text Available A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events, but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs, represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.

  11. 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.

  12. 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

  13. Mast cell degranulation – a mechanism for the anti-arrhythmic effect of endothelin-1?

    Science.gov (United States)

    Walsh, SK; Kane, KA; Wainwright, CL

    2009-01-01

    Background and purpose: The aim of this study was to investigate whether the previously reported anti-arrhythmic effect of endothelin-1 (ET-1) is mediated by degranulation of cardiac mast cells prior to myocardial ischaemia. Experimental approach: Male Sprague-Dawley rats received either ET-1 (1.6 nmol·kg−1) in the presence or absence of disodium cromoglycate (DSCG; 20 mg·kg−1·h−1) prior to coronary artery occlusion (CAO). In separate experiments rats were given compound 48/80 (50 µg·kg−1) to compare the effects of ET-1 with those of a known mast cell degranulator. Ischaemia-induced ventricular arrhythmias were detected through continuous monitoring of a lead I electrocardiogram. After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series of sham groups were performed to determine the direct effects of ET-1 and compound 48/80 on mast cell degranulation in the absence of ischaemia. Key results: ET-1 and compound 48/80 both exerted profound anti-arrhythmic effects, significantly reducing the total number of ventricular ectopic beats (P DSCG infusion prior to CAO. In sham animals ET-1 and compound 48/80 both induced mast cell degranulation (P DSCG, confirming their ability to induce degranulation of mast cells. Conclusions and implications: These results demonstrate for the first time that when given prior to ischaemia ET-1 mediates its anti-arrhythmic effects, at least in part, via cardiac mast cell degranulation. PMID:19422371

  14. Drug interaction as cause of spontaneously resolving epidural spinal hematoma on warfarin therapy

    Directory of Open Access Journals (Sweden)

    Amitabh Sagar

    2010-01-01

    Full Text Available We present a case of a 42-year-old male, an old case of deep vein thrombosis on warfarin and other drugs like quetiapine, aspirin, diclofenac sodium, fenofibrate, atorvastatin, propanolol and citalopram for concurrent illnesses, who presented with widespread mucocutaneous bleeding and epidural spinal hematoma. The epidural bleed presented clinically as a nontraumatic, rapidly improving myeloradiculopathy. Magnetic resonance imaging (MRI of the spine revealed an epidural hematoma at D12-L1 level. The case was managed conservatively due lack of neurosurgical facilities. The patient gained full neurological recovery on conservative management alone. This case highlights the problem of drug interaction on warfarin therapy and also an unusual spontaneous recovery of spinal hematoma. Our case was anticoagulated in the recommended therapeutic INR range of 2.2 to 2.4. Most of the similar cases reported in literature were also anticoagulated in the therapeutic range. Thus intraspinal hemorrhage is a rare but dangerous complication of anticoagulant therapy. It must be suspected in any patient on anticoagulant agents who complains of local or referred spinal pain associated with neurological deficits. Drug interactions with warfarin are common. High suspicion and immediate intervention are essential to prevent complications from intraspinal hemorrhage.

  15. Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses

    DEFF Research Database (Denmark)

    Haugaard, Maria Mathilde; Pehrson, S.; Carstensen, Helena;

    2015-01-01

    understood. OBJECTIVES: To study the potential of flecainide to terminate acutely induced AF of short duration (≥ 15 minutes), to examine flecainide-induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle...... length, and ventricular depolarization and repolarization. ANIMALS: Nine Standardbred horses. Eight received flecainide, 3 were used as time-matched controls, 2 of which also received flecainide. METHODS: Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5...

  16. Calcium antagonistic and antiarrhythmic actions of CPU-23, a substituted tetrahydroisoquinoline.

    OpenAIRE

    Dong, H.; Sheng, J. Z.; C. M. Lee; Wong, T. M.

    1993-01-01

    1. The effects of CPU-23 (1-(1-[(6-methoxyl)-naphth-2-yl])-propyl-2-(1-piperidine)-acetyl-6 ,7- dimethyoxy-1,2,3,4-tetra-hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone-anaesthetized rats subjected to coronary artery ligation were also evaluated. 2. CPU-23 at 10(-6...

  17. Viability of a Drug-Resistant Human Immunodeficiency Virus Type 1 Protease Variant: Structural Insights for Better Antiviral Therapy

    OpenAIRE

    Prabu-Jeyabalan, Moses; Ellen A. Nalivaika; King, Nancy M.; Schiffer, Celia A.

    2003-01-01

    Under the selective pressure of protease inhibitor therapy, patients infected with human immunodeficiency virus (HIV) often develop drug-resistant HIV strains. One of the first drug-resistant mutations to arise in the protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which compromises the binding of these and other inhibitors but allows the virus to remain viable. To probe this drug resistance, we solved the crystal structures of three natural substrates ...

  18. Achieving a Spiritual Therapy Standard for Drug Dependency in Malaysia, from an Islamic Perspective: Brief Review Article.

    Directory of Open Access Journals (Sweden)

    Tahereh Seghatoleslam

    2015-01-01

    Full Text Available Religion is one of the protective factors that facilities positive outcomes by preventing individuals from engaging in addictive substance. A recent study has confirmed that religion inhibits drug addiction. The concept of psychospiritual therapy was to introduce drug addiction. Therefore, of the various methods of psychotherapy, the usage of Taqwa (piety emerged as an applicable method of Islamic spiritual therapy. This study was conducted in Malaysia as a Muslim country and focuses on Islamic recommendations and its relation to spiritual therapy.

  19. Early rehabilitation and neuroprotective drug therapy outcomes in elderly patients with acute stroke

    Institute of Scientific and Technical Information of China (English)

    Yue Chen; Lufang Chen; Yiqing Tao; Feixue Zhou; Chunlan Cui; Shichao Liu

    2011-01-01

    Sixty elderly patients, who suffered from acute stroke and were admitted within a 1-year period to the Department of Geriatrics in the First Affiliated Hospital of School of Medicine, Zhejiang University, China, underwent early rehabilitation in combination with neuroprotective drug therapy. Limb movement, cognitive functions and daily life self-care ability in elderly patients upon admission and discharge were assessed using the Hunt-Hess scale, functional independence measures and mini-mental state examination. The mean duration of hospital stay among the 60 patients was 35 days. Upon discharge, 42 (75%) of the patients exhibited cognitive impairment to varying degrees, and 25 (45%) of the 56 stroke patients who underwent rehabilitation evaluation attained independence in daily living activities, 11 (20%) required intermittent supervision, and 20 (36%) required 24-hour constant supervision during performance of these activities. Results demonstrated that early rehabilitation treatment in combination with neuroprotective therapy for acute stroke was effective.

  20. Electromotive drug administration for treatment of therapy-refractory overactive bladder

    Directory of Open Access Journals (Sweden)

    A. Gauruder Burmester

    2008-12-01

    Full Text Available PURPOSE: Evaluate the benefits of electromotive drug administration (EMDA as an alternative technique in patients with chronic overactive bladder in terms of improvement of symptoms, quality of life, and sexuality. MATERIAL AND METHODS: A total of 72 patients with therapy-refractory overactive bladder according to the ICS (International Continence Society definition, were treated by EMDA. The regimen consisted of three treatment cycles, each with 3 instillations at 2-week intervals. The solution instilled consisted of 100 mL 4% lidocaine, 100 mL distilled water, 40 mg dexamethasone, and 2 mL epinephrine. Peri-interventionally, a urine test and close circulatory monitoring were performed. All women underwent urodynamic testing and cystoscopy and kept a voiding diary. A comprehensive history was obtained, a quality of life questionnaire administered, and a gynecologic examination performed before initiation of therapy. The women underwent follow-up at 12 months after the end of therapy. RESULTS: The patients had a mean age of 63 (± 11.2 years. Bladder capacity improved significantly by 109 mL (± 55 mL in 51 (71% patients (p = 0.021. The number of micturitions/day decreased significantly to 7 (± 2 (p = 0.013. Quality of life was improved in 54 patients (75%; p = 0.024 and sexuality in 39 (54%; p = 0.020. CONCLUSIONS: The results suggest that EMDA can improve both quality of life and sexuality in patients with therapy-refractory chronic overactive bladder.

  1. Dofetilide: a class III anti-arrhythmic drug for the treatment of atrial fibrillation

    DEFF Research Database (Denmark)

    Torp-Pedersen, C; Brendorp, B; Køber, L

    2000-01-01

    dofetilide. After pharmacological or electrical conversion of atrial fibrillation to sinus rhythm in these studies, the probability of remaining in sinus rhythm during the following year was 75%. Dofetilide has a single significant side effect: risk of developing torsade de pointes ventricular tachycardia...... infarctions, only amiodarone and dofetilide have proven safety and dofetilide is a strong candidate for first choice treatment when the aim is to achieve sinus rhythm....

  2. Antiarrhythmic properties of novel antianginal drugs in dog and human cardiac preparations

    OpenAIRE

    Dr Szél Tamás

    2013-01-01

    Chronic stable angina is an insidious manifestation of coronary artery disease. Pharmacological treatment is the cornerstone of stable angina and is an essential component of the treatment strategy, which also involves beta-blockers, nitrates (or related derivatives) and calcium channel blockers. New classes of treatments (ivabradine, ranolazine) with entirely different mechanisms of action have now been added. Ranolazine reduces ischemia via inhibition of the late phase of the inward sodium ...

  3. Adenylyl Cyclase Signaling in the Developing Chick Heart: The Deranging Effect of Antiarrhythmic Drugs

    Czech Academy of Sciences Publication Activity Database

    Hejnová, L.; Hahnová, K.; Kočková, Radka; Svatůňková, Jarmila; Sedmera, David; Novotný, J.

    2014-01-01

    Roč. 2014, č. 2014 (2014), s. 463123. ISSN 2314-6133 R&D Projects: GA ČR(CZ) GAP302/11/1308 Institutional support: RVO:67985823 Keywords : embryonic heart * embryotoxicity * adenylyl cyclase * G protein * beta-blocking agents Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.579, year: 2014

  4. Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo

    Czech Academy of Sciences Publication Activity Database

    Kočková, Radka; Svatůňková, Jarmila; Novotný, J.; Hejnová, L.; Ošťádal, Bohuslav; Sedmera, David

    2013-01-01

    Roč. 304, č. 6 (2013), H895-H902. ISSN 0363-6135 R&D Projects: GA ČR(CZ) GAP302/11/1308; GA ČR(CZ) GA304/08/0615 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : beta-blocking agents * embryonic heart * embryotoxicity * pregnancy * bradycardia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.012, year: 2013

  5. Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip.

    Science.gov (United States)

    Doryab, Ali; Amoabediny, Ghassem; Salehi-Najafabadi, Amir

    2016-01-01

    Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. PMID:26875777

  6. Cell-targeted 114Inm and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    A proportion of syngeneic female rats inoculated intramuscularly with a lethal T-cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine)(10 mg kg-1) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide 114Inm, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells. (author)

  7. 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

  8. 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 OBJECTIVE: 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. DESIGN: Cross-sectional cohort study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  9. A dual-targeting drug co-delivery system for tumor chemo- and gene combined therapy.

    Science.gov (United States)

    Zhang, Fangrong; Li, Min; Su, Yujie; Zhou, Jianping; Wang, Wei

    2016-07-01

    Regulation of gene expression using p53 is a promising strategy for treatment of numerous cancers, and chemotherapeutic drug dichloroacetate (DCA) induces apoptosis and growth inhibition in tumor, without apparent toxicity in normal tissues. Combining DCA and p53 gene could be an effective way to treat tumors. The progress towards broad applications of DCA/p53 combination requires the development of safe and efficient vectors that target to specific cells. In this study, we developed a DSPE-PEG-AA (1,2-distearoryl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000)] ammonium salt-anisamide) modified reconstituted high-density lipoprotein-based DCA/p53-loaded nanoparticles (DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes), which was fabricated as a drug/gene dual-targeting co-delivery system for potential cancer therapy. Here, DCA-PEI was utilized to effectively condense the p53 plasmid, to incorporate the plasmid into rHDL and to act as an antitumor drug to inhibit tumor cell growth. The DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes exhibited desirable and homogenous particle size, neutral surface charge and low cytotoxicity for normal cells in vitro. The results of confocal laser scanning microscopy (CLSM) and flow cytometry confirmed that the scavenger receptor class B type I (SR-BI) and sigma receptor mediated dual-targeting function of the complexes inducing efficient cytoplasmic drug delivery and gene transfection in human lung adenocarcinoma cell line A549. And in vivo investigation on nude mice bearing A549 tumor xenografts revealed that DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes possessed specific tumor targeting and strong antitumor activity. The work described here demonstrated that the DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes might offer a promising tool for effective cancer therapy. PMID:27127046

  10. Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Hinkle, G.H.; Basmadjian, G.P.; Peek, C.; Barker, K.K.; Ice, R.D.

    1982-11-01

    Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate.

  11. Targeting AMPK Signaling Pathway to Overcome Drug Resistance for Cancer Therapy.

    Science.gov (United States)

    Wang, Zhiyu; Liu, Pengxi; Chen, Qianjun; Deng, Shigui; Liu, Xiaoyan; Situ, Honglin; Zhong, Shaowen; Hann, Swei; Lin, Yi

    2016-01-01

    Mulitdrug resistance (MDR) is one of critical factorslimiting the efficacy of cancer chemoor radiotherapy. Emerging evidence has indicated that MDR is a complex process regulated by multiple factors, among which stress response molecules are considered as central players. AMP-activated protein kinase (AMPK) is a major regulator balancing energy supply and ultimately protects cells from harmful stresses via coordinating multiple metabolic pathways Notably, AMPK activation was recently shown to mediate the metabolism reprogramming in drug resistant cancer cells including promoting Warburg effects and mitochondrial biogenesis. Furthermore, AMPK activity has also been shown to regulate the self-renewal ability of cancer stem cells that are often refractory to chemotherapy. In addition, AMPK phosphorylation was critical in mediating autophagy induction, a process demonstrated to be effective in chemosensitivity modulation via degrading cellular components to satisfy nutrients requirement under stressful condition. Meanwhile, drug discovery targeting AMPK has been developed to validate the pathological significance of AMPK in cancer prevention and treatment. Although conflicting evidence focusing on the AMPK modulation for cancer treatment is still remained, this might be attributed to differences in AMPK isotypes in specific tissues, off-targets effects, the degree and duration of drug administration and experimental setting of stress conditions. This review will focus on AMPK mediated resistance to cancer therapy and discuss its potential therapeutic implication and targeting drug development. PMID:25777274

  12. 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.

  13. Targeted Tumor Therapy with "Magnetic Drug Targeting": Therapeutic Efficacy of Ferrofluid Bound Mitoxantrone

    Science.gov (United States)

    Alexiou, Ch.; Schmid, R.; Jurgons, R.; Bergemann, Ch.; Arnold, W.; Parak, F.G.

    The difference between success or failure of chemotherapy depends not only on the drug itself but also on how it is delivered to its target. Biocompatible ferrofluids (FF) are paramagnetic nanoparticles, that may be used as a delivery system for anticancer agents in locoregional tumor therapy, called "magnetic drug targeting". Bound to medical drugs, such magnetic nanoparticles can be enriched in a desired body compartment (tumor) using an external magnetic field, which is focused on the area of the tumor. Through this form of target directed drug application, one attempts to concentrate a pharmacological agent at its site of action in order to minimize unwanted side effects in the organism and to increase its locoregional effectiveness. Tumor bearing rabbits (VX2 squamous cell carcinoma) in the area of the hind limb, were treated by a single intra-arterial injection (A. femoralis) of mitoxantrone bound ferrofluids (FF-MTX), while focusing an external magnetic field (1.7 Tesla) onto the tumor for 60 minutes. Complete tumor remissions could be achieved in these animals in a dose related manner (20% and 50% of the systemic dose of mitoxantrone), without any negative side effects, like e.g. leucocytopenia, alopecia or gastrointestinal disorders. The strong and specific therapeutic efficacy in tumor treatment with mitoxantrone bound ferrofluids may indicate that this system could be used as a delivery system for anticancer agents, like radionuclids, cancer-specific antibodies, anti-angiogenetic factors, genes etc.

  14. Hydrophilic mesoporous carbon nanospheres with high drug-loading efficiency for doxorubicin delivery and cancer therapy

    Science.gov (United States)

    Wang, Huan; Li, Xiangui; Ma, Zhiqiang; Wang, Dan; Wang, Linzhao; Zhan, Jieqiong; She, Lan; Yang, Feng

    2016-01-01

    In this study, a highly effective transmembrane delivery vehicle based on PEGylated oxidized mesoporous carbon nanosphere (oMCN@PEG) was successfully fabricated in a facile strategy. oMCN@PEG exhibited a narrow size distribution of 90 nm, excellent hydrophilicity, good biocompatibility, and a very high loading efficiency for doxorubicin (DOX). The drug system (oMCN@DOX@PEG) exhibited excellent stability under neutral pH conditions, but with dramatic releases of DOX at reduced pH conditions. Pharmacokinetics study revealed that oMCN@DOX@PEG could prolong the circulation of DOX in the blood stream. The endocytosis, cytotoxicity, and anticancer effect in vitro and in vivo of the drug-loaded nanoparticles were also evaluated. Our results showed that the nanoparticles efficiently penetrated the membrane of tumor cells, subsequently released drugs, and efficiently inhibited the growth of cancer cells both in vitro and in vivo. Especially, oMCN@DOX@PEG also exhibited significant antimetastasis effect in advanced stage of malignant cancer, improving the survival time of tumor-bearing mice. The results suggested that oMCN@PEG might be a promising anticancer drug delivery vehicle for cancer therapy. PMID:27175077

  15. 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.

  16. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes.

    Science.gov (United States)

    Hallett, Rachel L; Sutherland, Colin J; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J; Pinder, Margaret; Walraven, Gijs; Targett, Geoffrey A T; Alloueche, Ali

    2004-10-01

    Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resistant parasites from treated patients to mosquito vectors has not been measured directly. In a trial comparing CQ monotherapy to the combination CQ plus artesunate (AS) in Gambian children with uncomplicated falciparum malaria, we measured transmissibility by feeding Anopheles gambiae mosquitoes with blood from 43 gametocyte-positive patients through a membrane. In the CQ-treated group, gametocytes from patients carrying parasites with the CQ resistance-associated allele pfcrt-76T prior to treatment produced infected mosquitoes with 38 times higher Plasmodium falciparum oocyst burdens than mosquitoes fed on gametocytes from patients infected with sensitive parasites (P < 0.001). Gametocytes from parasites carrying the resistance-associated allele pfmdr1-86Y produced 14-fold higher oocyst burdens than gametocytes from patients infected with sensitive parasites (P = 0.011). However, parasites carrying either of these resistance-associated alleles pretreatment were not associated with higher mosquito oocyst burdens in the CQ-AS-treated group. Thus, combination therapy overcomes the transmission advantage enjoyed by drug-resistant parasites. PMID:15388456

  17. Monitoring early tumor response to drug therapy with diffuse optical tomography

    Science.gov (United States)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  18. Potential of using boric acid as a boron drug for boron neutron capture therapy for osteosarcoma

    International Nuclear Information System (INIS)

    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 μg 10B/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 10B/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.

  19. 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 

  20. Personalized therapy with TNF-inhibitors in Crohn's disease: optimizing treatment outcomes by monitoring drug levels and anti-drug antibodies.

    Science.gov (United States)

    Steenholdt, Casper

    2016-08-01

    Therapeutic monoclonal antibodies (Abs) targeting the proinflammatory cytokine, TNF-α have revolutionized the treatment of inflammatory bowel disease (IBD), and raised treatment goals from symptom control to maintenance of clinical remission with mucosal healing. However, clinicians are challenged by a significant proportion of patients not responding to TNF-inhibitors or losing effect over time, and by the high costs of these drugs along with their potential side effects. The aim of this dissertation was therefore to examine if anti-TNF treatment outcomes can be improved by tailoring therapy on an individual patient basis by considering relevant prognostic variables. The main finding is that personalized treatment with TNF-inhibitors by use of an algorithm defined by measurements of anti-TNF drug and anti-drug Abs to guide interventions at therapeutic failure can be useful to secure optimal clinical, economic, and patient reported outcomes. Furthermore, the present studies have documented the key role of measurements of anti-TNF drug and anti-drug Abs to elucidate conditions related to pharmacokinetics and pharmacodynamics of these agents in individual patients, and to serve as prognostic markers of anti-TNF treatment outcomes. In addition, knowledge has been provided on how to interpret and integrate measurements of anti-TNF drug and anti-drug Abs in the clinical management of individual IBD patients taking into account potential pit-falls and biases. Hence, the studies forming the basis for this dissertation have yielded novel insights into the technical, temporal, and methodological complexities and challenges related to application of personalized anti-TNF treatment strategies based on measurements of anti-TNF drug and anti-drug Abs, and established measures to proactively address and accommodate these - both technically and clinically. Although not yet completely resolved, this dissertation has also laid a foundation for individually tailored anti

  1. Drug: D02086 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02086 Drug Lidocaine injection (JP16); Lidocaine hydrochloride (JAN/USP); Dalcaine...1 D04AB01] D02086 Lidocaine hydrochloride (JAN/USP) CAS: 73-78-9 PubChem: 7849147 DrugBank: DB00281 LigandBo...CYP2D6 [HSA:1565] Transporter: SLC22A3 [HSA:6581] map07037 Antiarrhythmic drugs m...ap07231 Sodium channel blocking drugs Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting...Xylidines D02086 Lidocaine injection (JP16); Lidocaine hydrochloride (JAN/USP) 2 Agents affecting individual

  2. Enhanced effect of photodynamic therapy in ovarian cancer using a nanoparticle drug delivery system.

    Science.gov (United States)

    Li, Zhao; Sun, Liping; Lu, Zaijun; Su, Xuantao; Yang, Qifeng; Qu, Xun; Li, Li; Song, Kun; Kong, Beihua

    2015-09-01

    Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ascites model using Fischer 344 rats and PBCA-NP entrapped with HB (HB-PBCA-NP) were formed successfully. The pharmacodynamic characteristics and biodistribution of the HB-PBCA-NP system were evaluated by comparison with HB dimethyl sulfoxide (HB-DMSO) and testing at various time-points following intraperitoneal drug administration. HB-PBCA-NP-based PDT combined with cytoreductive surgery was then administrated to the tumor-bearing animals. Kaplan-Meier survival analysis was performed to assess the therapeutic effect of the nanoparticle system. The serum HB concentration peaked 4 h after drug administration in the nanoparticle system, and 1 h with HB-DMSO. The peak exposure time of tumor tissues was also extended (4 vs. 2 h), and PBCA-NP remained present for much longer than HB-DMSO. Although PDT combined with surgery prolonged the survival time significantly compared with surgery alone (84 days, Panimals that received either HB-PBCA-NP- or HB-DMSO-based PDT after cytoreductive surgery (99 vs. 95 days, P=0.293). PBCA-NP exhibited potential advantages in controlled drug release and tumor targeting, which was beneficial for HB-based PDT. PDT combined with surgery prolonged the survival time, suggesting that this might be an alternative treatment option for ovarian cancer. PMID:26165140

  3. Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

    International Nuclear Information System (INIS)

    Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission

  4. Cost-effectiveness-analysis: radioiodine or antithyroid drugs as first-line therapy of hyperthyroidism due to Graves' disease

    International Nuclear Information System (INIS)

    Aim: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. Method: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq I-131 residual activity. Result: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. Conclusion: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake). (orig.)

  5. 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

  6. An individual drug-therapy and genetic testing report of temporal bone verrucous carcinoma

    Directory of Open Access Journals (Sweden)

    Tan HL

    2014-09-01

    Full Text Available Haolei Tan, Yong Liu, Gangcai Zhu, Leiming Pi, Donghai Huang, Xin Zhang Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China Objective: To investigate the pathology and pathogenesis of and treatment methods for temporal bone verrucous carcinoma. Materials and methods: A single-patient report of verrucous carcinoma on the left external auditory canal is presented and analyzed along with all cases of temporal bone verrucous carcinoma that have been documented in the English literature. Results: Most of the patients with verrucous carcinoma of the temporal bone have histories of surgery, trauma, or infection, and verrucous carcinomas are sensitive to antimicrotubule chemotherapeutic medicines. Adjuvant radiation therapy is not effective, but surgical treatment might be relatively more effective. Conclusion: Temporal bone verrucous carcinoma has a poor prognosis; therefore, the preferred treatment is surgical resection facilitated with antimicrotubule chemotherapeutic treatment. Adjuvant radiation therapy is not a preferred treatment for temporal bone verrucous carcinoma. Keywords: verrucous carcinoma, temporal bone, drug therapy, genetic testing

  7. Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo

    Science.gov (United States)

    Liu, Yun; Ding, Xingwei; Li, Jinghua; Luo, Zhong; Hu, Yan; Liu, Junjie; Dai, Liangliang; Zhou, Jun; Hou, Changjun; Cai, Kaiyong

    2015-04-01

    To reduce the toxic side effects of traditional chemotherapeutics in vivo, we designed and constructed a biocompatible, matrix metalloproteinases (MMPs) responsive drug delivery system based on mesoporous silica nanoparticles (MSNs). MMPs substrate peptide containing PLGLAR (sensitive to MMPs) was immobilized onto the surfaces of amino-functionalized MSNs via an amidation reaction, serving as MMPs sensitive intermediate linker. Bovine serum albumin was then covalently coupled to linker as end-cap for sealing the mesopores of MSNs. Lactobionic acid was further conjugated to the system as targeting motif. Doxorubicin hydrochloride was used as the model anticancer drug in this study. A series of characterizations revealed that the system was successfully constructed. The peptide-functionalized MSNs system demonstrated relatively high sensitivity to MMPs for triggering drug delivery, which was potentially important for tumor therapy since the tumor’s microenvironment overexpressed MMPs in nature. The in vivo experiments proved that the system could efficiently inhibit the tumor growth with minimal side effects. This study provides an approach for the development of the next generation of nanotherapeutics toward efficient cancer treatment.

  8. Practical Use of Newer Antiepileptic Drugs as Adjunctive Therapy in Focal Epilepsy.

    Science.gov (United States)

    Brodie, Martin J

    2015-11-01

    This article lays the background for, and discusses the practical issues surrounding, the adjunctive use of the last four antiepileptic drugs (AEDs) to be licensed for the treatment of pharmacoresistant focal seizures in the UK and elsewhere. More than 30% of adolescent and adult patients will not be fully controlled on the currently available therapeutic armamentarium. After not responding to their first three AED schedules, only a handful of patients attained seizure freedom on subsequent regimens. To optimise the response to any new AED in this setting, it is often necessary to reduce the existing drug burden. The pharmacology, tolerability and safety, and everyday use of lacosamide, eslicarbazepine acetate, retigabine (ezogabine) and perampanel will be reviewed and discussed. This will be accompanied by data from prospective audits with each drug undertaken at the Western Infirmary in Glasgow, Scotland, and a report of their successful introduction in an illustrative case. Overall, there is a large variation in the course of refractory epilepsy and the effect of AED therapy on this process seems minimal. Nevertheless, a number of patients will benefit from the introduction of each new AED, with some becoming seizure-free. PMID:26507832

  9. Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo

    International Nuclear Information System (INIS)

    To reduce the toxic side effects of traditional chemotherapeutics in vivo, we designed and constructed a biocompatible, matrix metalloproteinases (MMPs) responsive drug delivery system based on mesoporous silica nanoparticles (MSNs). MMPs substrate peptide containing PLGLAR (sensitive to MMPs) was immobilized onto the surfaces of amino-functionalized MSNs via an amidation reaction, serving as MMPs sensitive intermediate linker. Bovine serum albumin was then covalently coupled to linker as end-cap for sealing the mesopores of MSNs. Lactobionic acid was further conjugated to the system as targeting motif. Doxorubicin hydrochloride was used as the model anticancer drug in this study. A series of characterizations revealed that the system was successfully constructed. The peptide-functionalized MSNs system demonstrated relatively high sensitivity to MMPs for triggering drug delivery, which was potentially important for tumor therapy since the tumor’s microenvironment overexpressed MMPs in nature. The in vivo experiments proved that the system could efficiently inhibit the tumor growth with minimal side effects. This study provides an approach for the development of the next generation of nanotherapeutics toward efficient cancer treatment. (paper)

  10. 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

  11. Methotrexate conjugated magnetic nanoparticle for targeted drug delivery and thermal therapy

    Science.gov (United States)

    Gupta, Jagriti; Bhargava, Parag; Bahadur, D.

    2014-05-01

    A simple soft chemical approach is used for the preparation of citrate functionalized iron oxide (Fe3O4) aqueous colloidal magnetic nanoparticles (CA-MNPs) of average size ˜10 nm. The CA-MNPs exhibit superparamagnetic behavior at room temperature with strong field dependent magnetic responsivity. The CA-MNPs can be conjugated with Methotrexate (MTX) drug through amide bonds between the carboxylic group on the surface of MNPs and amine group of MTX. The surface functionalization of Fe3O4 nanoparticles with citric acid and conjugation of MTX drug is evident from FTIR spectroscopy, zeta-potential measurement, and elemental and thermal analyses. From the drug release study, it has been observed that this bonding of MTX conjugated MNPs (MTX-MNPs) is cleaved by the intracellular enzymes in lysosome, and MTX is delivered largely inside target cancerous cells at lower pH, thereby reducing toxicity to normal cells. Also, it has been observed that the intercellular uptake of MTX-MNPs is higher compared to CA-MNPs. In addition, the aqueous colloidal stability, optimal magnetization, and good specific absorption rate (under external AC magnetic field) of CA-MNPs act as effective heating source for thermal therapy. Cytotoxicity study of MTX-MNPs shows the reduction of cellular viability for human cervical cancer cells (HeLa). Further, a synergistic effect of MTX-MNPs shows a more effective tumor cell death due to the combined effect of thermo-chemotherapy.

  12. Antibody therapy alone and in combination with targeted drugs in chronic lymphocytic leukemia.

    Science.gov (United States)

    Robak, Tadeusz; Blonski, Jerzy Z; Robak, Pawel

    2016-04-01

    The development of non-chemotherapeutic agents, including monoclonal antibodies (mAbs) and other targeted drugs, makes chemotherapy-free treatment an attractive option for chronic lymphocytic leukemia (CLL). The classical mAb, rituximab, has been authorized for use in both first-line and second-line therapy for CLL. New mAbs directed against CD20, ofatumumab, and obinutuzumab (GA-101) have also been approved for the treatment of this disease. Recently, several new mAbs with potential benefits over the approved anti-CD20 antibodies have been developed for use in CLL. Anti-CD37, anti-CD19, and anti-CD40 mAbs are in early clinical trials and show promise in treating CLL. In addition, the combination of mAbs with B-cell receptor signaling pathway inhibitors and immunomodulatory drugs makes the chemotherapy-free option a reality today. Combinations of antibodies with targeted drugs like ibrutinib, idelalisib, or lenalidomide are expected to replace chemotherapy-based combinations for treating CLL in the near future. However, phase III trials should confirm the benefit of these new treatment strategies and establish their exact place in the therapeutic armamentarium for CLL. PMID:27040707

  13. 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.

  14. NEBULIZATION THERAPY - A NOVEL APPROACH TO DRUG DELIVERY SYSTEM IN AYURVEDA

    Directory of Open Access Journals (Sweden)

    Kajaria Divya Kumari

    2011-11-01

    Full Text Available Several route of administration of drug have not only been described in Ayurvedic texts but also practiced for several millennia. Depending upon physical property of the drug it can be rubbed on the skin like lotion or it can be instilled in the form of drops like nasal (nasya/ ear (karnapurana drop etc. It can be swallowed in the form of tablets and also it can be injected directly into the bloodstream. Similarly the medicines can also be administered through nasal route using nebulization technique or through meter dose inhalation.The process of Nebulization involves a suspension of fine vaporized liquid droplets--otherwise known as aerosol--to administer fluids, oxygen and liquid medication directly to the respiratory system. Nebulizers are commonly used for treatment of cystic fibrosis, asthma, COPD and other respiratory diseases. Breakthroughs in the treatment of Asthma came in light with the introduction of Inhalation therapy (Nebulization / Aerosol mode of drug administration in the conventional medicine. There are several plus points for through-the-lung delivery of medication. The lungs have a large surface area, so that absorption is fast and ample. Lungs are quite tolerant to foreign substances like powders of tobacco, smoke, and fragrances of a hundred types by common men. Lungs are much more permeable than skin, nasal mucosa or the gastro-intestinal tract. This mode of administration proves to be highly beneficial in saving life in acute life threatening condition such as “Status Asthmatics”. But wide range of toxic side effects of modern medicine confines its use as permanent remedy. Administration of drug through nasal route is highly prevalent also in Ayurveda. Since ancient time Acharays very well knew the importance and effectiveness of this route as they had said that“Nasa hi Shirsodvaram”. There are numerous variety of drugs mentioned in Ayurvedic text which can be administered through Nasal route, namely Nasya and

  15. Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles

    Science.gov (United States)

    Baek, Seonmi; Singh, Rajendra K.; Khanal, Dipesh; Patel, Kapil D.; Lee, Eun-Jung; Leong, Kam W.; Chrzanowski, Wojciech; Kim, Hae-Won

    2015-08-01

    Nanomedicine seeks to apply nanoscale materials for the therapy and diagnosis of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery of therapeutic agents only to the specific site. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in a discreet manner and interact with cells/tissues only locally. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems - theranostics - holds great promise to minimise side effects and boost therapeutic effectiveness of the treatment. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides a comprehensive review of the state-of-the-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications.

  16. Drug-Drug Interactions Based on Pharmacogenetic Profile between Highly Active Antiretroviral Therapy and Antiblastic Chemotherapy in Cancer Patients with HIV Infection.

    Science.gov (United States)

    Berretta, Massimiliano; Caraglia, Michele; Martellotta, Ferdinando; Zappavigna, Silvia; Lombardi, Angela; Fierro, Carla; Atripaldi, Luigi; Muto, Tommaso; Valente, Daniela; De Paoli, Paolo; Tirelli, Umberto; Di Francia, Raffaele

    2016-01-01

    The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the natural approach of HIV-related cancers. Several studies have shown that intensive antiblastic chemotherapy (AC) is feasible in HIV-infected patients with cancer, and that the outcome is similar to that of HIV-negative patients receiving the same AC regimens. However, the concomitant use of HAART and AC can result in drug accumulation or possible toxicity with consequent decreased efficacy of one or both classes of drugs. In fact, many AC agents are preferentially metabolized by CYP450 and drug-drug interactions (DDIs) with HAART are common. Therefore, it is important that HIV patients with cancer in HAART receiving AC treatment at the same time receive an individualized cancer management plan based on their liver and renal functions, their level of bone marrow suppression, their mitochondrial dysfunction, and their genotype profile. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, in order to maximize the efficacy of antiblastic therapy and minimize the risk of drug-drug interaction, a useful list of pharmacogenomic markers is provided. PMID:27065862

  17. Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation.

    Science.gov (United States)

    Ji, Tianjiao; Zhao, Ying; Ding, Yanping; Wang, Jing; Zhao, Ruifang; Lang, Jiayan; Qin, Hao; Liu, Xiaoman; Shi, Jian; Tao, Ning; Qin, Zhihai; Nie, Guangjun; Zhao, Yuliang

    2016-01-18

    A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein-α (FAP-α), a protease specifically expressed on the surface of cancer-associated fibroblasts. The CAP self-assembled into fiber-like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug-loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP-NPs) upon FAP-α cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers-like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug-loaded CAP-NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy. PMID:26283097

  18. Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

    OpenAIRE

    Ponizovskiy MR

    2015-01-01

    “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 mit...

  19. Recent advances in drug therapy for myopia%近视眼药物治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    许瑶; 曾骏文

    2013-01-01

    本文回顾了最近国内外近视眼药物治疗的相关研究,从常见药物治疗和针对脉络膜新生血管的治疗两方面作了介绍,并为未来的治疗方向提出了一些设想.本文主要介绍了阿托品、哌仑西平、阿扑吗啡、7-甲基黄嘌呤等传统药物的新用法,同时也阐述了光动力疗法、单抗类药物用于近视治疗的最新研究进展.%This article reviews about recent advances of studies on drug therapy for myopia,introducing the common drug therapies and therapies for choroidal neovascularization.This article proposes some ideas of future treatment for myopia.This review introduces the new usage of some traditional drugs including atropine,pirenzepine,apomorphine,7-methylxanthine,and reviews the latest advances in studies on photodynamic therapy and monoclonal antibody drugs therapy for myopia.

  20. Activated Charge-Reversal Polymeric Nano-System: The Promising Strategy in Drug Delivery for Cancer Therapy

    OpenAIRE

    Yichen Hu; Xiao Gong; Jinming Zhang; Fengqian Chen; Chaomei Fu; Peng Li; Liang Zou; Gang Zhao

    2016-01-01

    Various polymeric nanoparticles (NPs) with optimal size, tumor-targeting functionalization, or microenvironment sensitive characteristics have been designed to solve several limitations of conventional chemotherapy. Nano-sized polymeric drug carrier systems have remarkably great advantages in drug delivery and cancer therapy, which are still plagued with severe deficiencies, especially insufficient cellular uptake. Recently, surface charge of medical NPs has been demonstrated to play an impor...

  1. A Cell-Targeted, Size-Photocontrollable, Nuclear-Uptake Nanodrug Delivery System for Drug-Resistant Cancer Therapy

    OpenAIRE

    Qiu, Liping; Chen, Tao; Öçsoy, Ismail; Yasun, Emir; Wu, Cuichen; Zhu, Guizhi; You, Mingxu; Han, Da; Jiang, Jianhui; Yu, Ruqin; Tan, Weihong

    2014-01-01

    The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell...

  2. Something new every day: defining innovation and innovativeness in drug therapy.

    Science.gov (United States)

    Aronson, Jeffrey K

    2008-01-01

    The word "innovation" comes from the Latin noun innovatio, derived from the verb innovare, to introduce [something] new. It can refer either to the act of introducing something new or to the thing itself that is introduced. In terms of commerce, it is defined in the Oxford English Dictionary as "the action of introducing a new product into the market; a product newly brought on to the market," a definition that illustrates both aspects of the word's meaning. "Innovativeness" is the property of being an innovation. Here I identify several different types of innovativeness in drug therapy, including structural, pharmacological or pharmacodynamic, pharmaceutical, and pharmacokinetic innovativeness, and I stress the over-riding importance of clinical innovativeness, which should result in a better benefit to harm balance at an affordable cost. PMID:18162799

  3. EFFECTIVENESS OF FIXED DRUG COMBINATION ANTI-RETROVIRAL THERAPY IN HIV INFECTED CHILDREN: AN EXPLORATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Somasekhar Rao

    2015-10-01

    Full Text Available Over 90 per cent of HIV infected babies were born to HIV positive mothers in Sub-Saharan Africa and worldwide. It is estimated that currently 2.3 million i.e 5.9% are children less than 15 yrs of age infected with HIV. Worldwide, children under age 15 who were newly infected with HIV, more than 90 percent were babies were born to HIV-positive women. An estimated 1500 children get newly infected with HIV each day globally. The scenario is similar at home in Andhra Pradesh, India. This present exploratory study is to find out the effectiveness of fixed drug combination of antiretroviral therapy in children. The results are encouraging and are similar to results from such studies elsewhere.

  4. Importance of the long-acting partner drug in artemisinin-based combination therapy.

    Science.gov (United States)

    Kurtzhals, Jørgen Al

    2008-11-01

    The 1st African Health Research Organization International Malaria Symposium on Clinical Pharmacology of Antimalarial Drugs collected approximately 60 health professionals, scientists, policy makers and nongovernmental organization representatives from Africa, Europe and the USA for updates on recent developments in malaria therapy. It was the first African Health Research Organization symposium in Africa aimed at taking an African leadership in the fight against malaria. The intention is to start a tradition of annually recurring symposia that will eventually grow to become a leading international event in malaria research. Apart from scientific presentations, substantial time was dedicated to discussions and brainstorming, with a view to developing tools that can realistically be used to address challenges relating to all aspects of malaria treatment and control. The meeting was funded partly by the Medicines for Malaria Venture and Dafra Pharma International Ltd., Belgium, both of which were represented by some of the speakers. PMID:24410604

  5. A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy

    Science.gov (United States)

    Wei, Yanchun; Zhou, Feifan; Zhang, Da; Chen, Qun; Xing, Da

    2016-02-01

    Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in

  6. Multifunctionalized mesoporous silica nanoparticles for the in vitro treatment of retinoblastoma: Drug delivery, one and two-photon photodynamic therapy.

    Science.gov (United States)

    Gary-Bobo, Magali; Mir, Youssef; Rouxel, Cédric; Brevet, David; Hocine, Ouahiba; Maynadier, Marie; Gallud, Audrey; Da Silva, Afitz; Mongin, Olivier; Blanchard-Desce, Mireille; Richeter, Sébastien; Loock, Bernard; Maillard, Philippe; Morère, Alain; Garcia, Marcel; Raehm, Laurence; Durand, Jean-Olivier

    2012-08-01

    In this work, we focused on mesoporous silica nanoparticles (MSN) for one photon excitated photodynamic therapy (OPE-PDT) combined with drug delivery and carbohydrate targeting applied on retinoblastoma, a rare disease of childhood. We demonstrate that bitherapy (camptothecin delivery and photodynamic therapy) performed with MSN on retinoblastoma cancer cells was efficient in inducing cancer cell death. Alternatively MSN designed for two-photon excited photodynamic therapy (TPE-PDT) were also studied and irradiation at low fluence efficiently killed retinoblastoma cancer cells. PMID:22569231

  7. Adolescent and parent alliances with therapists in Brief Strategic Family Therapy with drug-using Hispanic adolescents.

    Science.gov (United States)

    Robbins, Michael S; Mayorga, Carla C; Mitrani, Victoria B; Szapocznik, José; Turner, Charles W; Alexander, James F

    2008-07-01

    This study examined the relationship between alliance and retention in family therapy. Alliance was examined at the individual (parent, adolescent) and family level (within-family differences) for families that either dropped out or completed family therapy. Participants were 31 Hispanic adolescents and their family members who received brief strategic family therapy for the treatment of adolescent drug use. Videotapes of first sessions were rated to identify parent and adolescent alliances with the therapist. Results demonstrated that Completer cases had significantly higher levels of alliance across all family members than Dropout cases, and Dropout cases had significantly higher unbalanced alliances than Completer cases. Clinical implications are discussed. PMID:18717922

  8. Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

    Science.gov (United States)

    Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

    2015-12-10

    Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI. PMID:26343846

  9. Comparative evaluation of antioxidant drug influence on a radio therapy efficiency and oxidative status in mice

    Directory of Open Access Journals (Sweden)

    Alexander V. Siprov

    2013-09-01

    Full Text Available The aim of the study is a comparative analysis of the effect of melatonin (Melaxen and 3-hydroxypyridine (Mexidol on antitumor and antimetastatic influence of chemoradiotherapy and oxidative status at mice with Lewis lung carcinoma. Material — Experiments have been organized on 95 mice of C57Bl/6 line and of 20–22 g in weight. Cyclophosphan has been abdominally administered two times in a dosage of 60 mg/kg within the interval of 120 hours — 20-30 min before radiotherapy. It has been located on the area of initial tumor in a dosage of 2 g at the same time as cyclophosphan injection. Melaxen and Mexidol have been intramuscularly injecting in the dosage of 45 and 50 mg/ kg for 14 days. Antitumor and antimetastatic effect of the applied therapy and changes in the oxidative status of the animals have been estimated. Results — Melaxen and Mexidol do not decrease antitumour and antimetastatic effects of radiotherapy and prevent the activation of free radical processes at animals with tumors. Mexidol was more effective than Melaxen in correction of superoxide dismutase activity in liver. The drugs under the study do not decrease radiotherapy-induced lipid peroxidation in the initial tumor. Conclusion — Melaxen and Mexidol do not decrease the radio therapy efficiency and oxidative status at mice with tumor (on the background of antitumor treatment.

  10. CLINICAL EFFICACY OF THE DRUG STRUCTUM IN OSTEOARTHRITIS THERAPY (results of multicenlral clinical study in Russia

    Directory of Open Access Journals (Sweden)

    V A Nassonova

    2001-01-01

    Full Text Available Objective. Study of the efficacy and tolerability of Structum in pts with gonarthritis and coxarthritis during 6 months therapy. Material. Open multicentral study included off -patients of both sexes with osteoarthritis (ОЛ of knee and hip joints with obvious pain syndrome - pain in walking 30 mm and more on visual analog scale, functional Lesquene index more or equal to 4 and less or equal toll, regular NSAIDs taking for 30 days for the last 3 months, radiological I-II-III OA stage according Kellgren-Lawrence and consent of the patient for the study. Total number of pts included was 555 and 192 out of them were experimental group and 363 - controls. Pts from experimental group had Structum - three capsules in the morning and 3 capsules in the evening during meals (one capsule - 250 mg for 3 weeks, then 2 capsules in the morning and 2 in the evening for 21 weeks. Clinical examination of pts was done after the third and sixth month of the treatment. Results. During Structum therapy reliable lessening of pain syndrome in knee and hip joints, improvement of articular function, decrease of NSAIDs dosage or their full cancellation were demonstrated. It was noticed that the assessment of clinical Structum efficacy and tolerability bu physician and patient coincided. Conclusion. Structum (chondroitin sulfate is a new effective drug for treatment of osteoarthritis of knee and hip joints with high clinical efficacy and good tolerability

  11. [Open questions in the drug therapy of tumors with new active substances].

    Science.gov (United States)

    Ludwig, Wolf-Dieter; Schott, Gisela

    2010-01-01

    At the time of market authorization and/or the expansion of indication of new oncology drugs, it is often not possible to reliably measure the relevant benefit for the patient. The conception of the clinical studies, on which the market authorization and/or expansion of indication is based, orients itself primarily at the regulatory requirements of the regulatory authorities. In addition, their results are frequently published only incompletely or some time after the end of the clinical study. To clarify these outstanding questions regarding the individual treatment of patients, independent,science-initiated clinical studies after the market authorization are required. However, the execution of these studies is obstructed due to insufficient financial means as well as by regulations and the low evaluation of such studies by the academia. Further challenges result from the high costs of innovative oncologic therapies, which burden the resources of the statutory and private health insurance providers(GKV, PKV) who are confronted with an aging population and a rising prevalence of tumor cases. Independent post-market authorization clinical studies need to be completed in order to ensure a need-oriented and efficient treatment with new oncologic substances. New perspectives result by connecting the reimbursement of the costs of innovative therapies by the GKV and PKV to the generation of evidence in the context of clinical studies, thus improving the medical care of tumor patients as well as the efficient handling of limited health resources. PMID:20926907

  12. 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.

  13. 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.

  14. 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. PMID:27423416

  15. Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death

    Directory of Open Access Journals (Sweden)

    David Vlahov

    2006-04-01

    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.

  16. 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.

  17. Developments and strategies for inhaled antibiotic drugs in tuberculosis therapy: a critical evaluation.

    Science.gov (United States)

    Hoppentocht, M; Hagedoorn, P; Frijlink, H W; de Boer, A H

    2014-01-01

    Inhaled antibiotics have been a valuable tool in treating pulmonary infections in cystic fibrosis patients for decades, and the pulmonary route is now becoming increasingly interesting for other infectious diseases like tuberculosis too. Especially with multidrug and extensively drug-resistant tuberculosis emerging, great effort is put into the improvement of pulmonary antibiotic administration to fight this global threat. Several reviews have been written on inhalable antibiotics, giving clear overviews of the compounds of interest. Furthermore, various formulation studies and administration strategies are on-going with these compounds. What is often missing is a critical evaluation of these developments. Several risks may be involved varying from obtaining insufficient local drug concentrations to adverse side effects and unwanted changes in physiological processes from the excipients used. In this manuscript, the pros and cons and feasibility of recent advances in pulmonary antibiotic tuberculosis therapy are presented and critically evaluated. Furthermore, the advantages of dry powder inhalation over wet nebulisation for inhaled antibiotics in developing countries where prevalence of tuberculosis is highest are discussed. It has to be concluded that a greater effort in good inhaler development and more research in the physico-chemical properties of the compounds of interest are needed. PMID:24189498

  18. 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

  19. Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

    International Nuclear Information System (INIS)

    Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

  20. High effectiveness of self-help programs after drug addiction therapy

    Directory of Open Access Journals (Sweden)

    Kristensen Øistein

    2006-08-01

    Full Text Available Abstract Background The self-help groups Alcoholics Anonymous (AA and Narcotics Anonymous (NA are very well established. AA and NA employ a 12-step program and are found in most large cities around the world. Although many have argued that these organizations are valuable, substantial scepticism remains as to whether they are actually effective. Few treatment facilities give clear recommendations to facilitate participation, and the use of these groups has been disputed. The purpose of this study was to examine whether the use of self-help groups after addiction treatment is associated with higher rates of abstinence. Methods One hundred and fourteen patients, 59 with alcohol dependency and 55 with multiple drug dependency, who started in self-help groups after addiction treatment, were examined two years later using a questionnaire. Return rate was 66%. Six (5% of the patients were dead. Results Intention-to-treat-analysis showed that 38% still participated in self-help programs two years after treatment. Among the regular participants, 81% had been abstinent over the previous 6 months, compared with only 26% of the non-participants. Logistic regression analysis showed OR = 12.6, 95% CI (4.1–38.3, p Conclusion The study has several methodological problems; in particular, correlation does not necessarily indicate causality. These problems are discussed and we conclude that the probability of a positive effect is sufficient to recommend participation in self-help groups as a supplement to drug addiction treatment. Previous publication This article is based on a study originally published in Norwegian: Kristensen O, Vederhus JK: Self-help programs in drug addiction therapy. Tidsskr Nor Laegeforen 2005, 125:2798–2801.

  1. [Exalief as a newer antiepileptic drug for adjunctive therapy of refractory partial-onset seizures].

    Science.gov (United States)

    Ermolenko, N A; Buchneva, I A

    2014-01-01

    Results of a multicenter international study on the efficacy of exalief (eslicarbazepine acetate (ESL)), a newer blocker of voltage-gated sodium channels and T-type voltage gated calcium channels, for adjunctive therapy of refractory partial-onset seizures are presented. A clinical program included phase II (BIA-2093-201) followed by three phase Ill studies (BIA-2093-301, -302 and-303), each of which was accompanied by an additional open one-year study (301 E, 302E, 303E). In three parallel phase Ill studies patients were randomized to receive ESL in single doses 400, 800, 1200 mg or placebo together with 1 - 3 antiepileptic drugs used in stable doses, with the exception of felbamate and oxcarbazepine. The design of the study included 8-week initial period, double-blind phase (2-week titration period, 12-week maintenance period), 4-week dose reduction period. The results of clinical phase II trials demonstrated the high efficacy and best tolerability profile for single dose titration regimen. Median changes in the frequency of partial-onset seizures were greater (p<0,0001) in patients receiving 800 and 1200 mg ESL (35 and 39%)compared to placebo (15%). The proportion of treatment responders was significantly higher in the groups treated with ESL indoses 800 mg (36%) and 1200 mg (44%) compared to the placebo group (22%). The aversive effects of the drug were of mild or moderate severity. Treatment retention was higher in patients receiving ESL (84,9% of patients completed the 6-month treatment period and 76,6% completed the one-year period). The use of ESL leads to the reduction in partial seizure frequency and the increase in the proportion of treatment responders. The drug has a good tolerability profile. PMID:25629136

  2. pH sensitive core-shell magnetic nanoparticles for targeted drug delivery in cancer therapy.

    Science.gov (United States)

    Lungu, Iulia Ioana; Rădulescu, Marius; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai

    2016-01-01

    In the last decade, nanobiotechnology has evolved rapidly with an extensive impact on biomedical area. In order to improve bioavailability and minimize adverse effects, drug delivery systems based on magnetic nanocomposites are under development mainly for cancer imaging and antitumor therapy. In this regard, pH sensitive core-shell magnetic nanoparticles (NPs) with accurate controlled size and shape are synthesized by various modern methods, such as homogeneous precipitation, coprecipitation, microemulsion or polyol approaches, high temperature and hydrothermal reactions, sol-gel reactions, aerosol÷vapor processes and sonolysis. Due to their unique combined physico-chemical and biological properties (such as higher dispensability, chemical and thermal stability, biocompatibility), pH responsive core-shell magnetic NPs are widely investigated for controlled release of cytostatic drugs into the tumor site by means of pH change: magnetite@silicon dioxide (Fe3O4@SiO2), Fe3O4@titanium dioxide (TiO2), β-thiopropionate-polyethylene glycol (PEG)-modified Fe3O4@mSiO2, Fe3O4 NPs core coated with SiO2 with an imidazole group modified PEG-polypeptide (mPEG-poly-L-Asparagine), polyacrylic acid (PAA) and folic acid (FA) coating of the iron oxide NP core, methoxy polyethylene glycol-block-polymethacrylic acid-block-polyglycerol monomethacrylate (MPEG-b-PMAA-b-PGMA) attached by a PGMA block to a Fe3O4 core, PEG-modified polyamidoamine (PAMAM) dendrimer shell with Fe3O4 core and mesoporous silica coated on Fe3O4, mostly coated with an anticancer drug. This review paper highlights the modern research directions currently employed to demonstrate the utility of the pH responsive core-shell magnetic NPs in diagnosis and treatment of oncological diseases. PMID:27151685

  3. Biological drugs targeting the immune response in the therapy of psoriasis

    Directory of Open Access Journals (Sweden)

    Saveria Pastore

    2008-08-01

    Full Text Available Saveria Pastore1, Emanuela Gubinelli2, Luca Leoni2, Desanka Raskovic2, Liudmila Korkina11Laboratory of Tissue Engineering and Cutaneous Physiopathology; 2Second Dermatology Unit, Istituto Dermopatico dell’Immacolata, IRCCS, Roma, ItalyAbstract: Chronic plaque psoriasis affects more than 2% of world population, has a chronic recurrent behavior, gives a heavy burden to the patients’ quality of life, and hence remains a huge medical and social problem. The clinical results of conventional therapies of psoriasis are not satisfactory. According to the current knowledge of the molecular and cellular basis of psoriasis, it is defined as an immune-mediated chronic inflammatory and hyperproliferative skin disease. A new generation of biological drugs, targeting molecules and cells involved into perturbed pro-inflammatory immune response in the psoriatic skin and joints, has been recently designed and applied clinically. These biological agents are bioengineered proteins such as chimeric and humanized antibodies and fusion proteins. In particular, they comprise the antitumor necrosis factor-α agents etanercept, infliximab, and adalimumab, with clinical efficacy in both moderate-severe psoriasis and psoriatic arthritis, and the anti-CD11a efalizumab with selective therapeutic action exclusively in the skin. Here, we overview recent findings on the molecular pathways relevant to the inflammatory response in psoriasis and present our clinical experience with the drugs currently employed in the dermatologic manifestations, namely etanercept, infliximab, and efalizumab. The growing body of clinical data on the efficacy and safety of antipsoriasis biological drugs is reviewed as well. Particular focus is given to long-term safety concerns and feasibility of combined therapeutic protocols to ameliorate clinical results.Keywords: psoriasis, immune-mediated inflammation, etanercept, infliximab, efalizumab

  4. Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic management of pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    P K Debnath

    2012-01-01

    Full Text Available Background: Pulmonary tuberculosis (PTB is an age old disease described in Vedic Medicine as ′Yakshma′. Later on, in Ayurveda it earned a prefix and found way into mythology as ′Rajayakshma′. After the discovery of streptomycin, the therapeutic management of PTB received a major breakthrough. The treatment module changed remarkably with the formulation of newer anti-tubercular drugs (ATD with appreciable success. Recent resurgence of PTB in developed countries like United States posed a threat to the medical community due to resistant strains. Consequently, WHO looked toward traditional medicine. Literature reveals that Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD with limited success. Records show that 2766 patients of PTB were treated with Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947. Objectives: To evaluate the toxicity reduction and early restoration by adjunct therapy of Ayurvedic drugs by increasing the bio-availability of ATDs. Materials and Methods: In the present study, treatment response of 99 patients treated with ATD as an adjunct with Aswagandha (Withania somnifera and a multi-herbal formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash were investigated. Hematological profile, sputum bacterial load count, immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine were the assessed parameters besides blood isoniazid and pyrazinamide, repeated after 28 days of treatment. Results: The symptoms abated, body weight showed improvement, ESR values were normal, there was appreciable change in IgA and IgM patterns and significantly increased bioavailability of isoniazid and pyrazinamide were recorded. Conclusion: This innovative clinical study coupled with empowered research may turn out to be promising in finding a solution for the treatment of PTB.

  5. Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy

    OpenAIRE

    Martínez, C; García-Martín, E; Pizarro, R M; García-Gamito, F J; Agúndez, J A G

    2002-01-01

    Cytochrome P450 3A is a drug-metabolising enzyme activity due to CYP3A4 and CYP3A5 gene products, that is involved in the inactivation of anticancer drugs. This study analyses the potential of cytochrome P450 3A enzyme in human colorectal cancer to impact anticancer therapy with drugs that are cytochrome P450 3A substrates. Enzyme activity, variability and properties, and the ability to inactivate paclitaxel (taxol) were analysed in human colorectal cancer and healthy colorectal epithelium. C...

  6. 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 and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes. PMID:27230510

  7. HIV-1 Drug Resistance Mutations Are Present in Six Percent of Persons Initiating Antiretroviral Therapy in Lusaka, Zambia

    NARCIS (Netherlands)

    R.L. Hamers; M. Siwale; C.L. Wallis; M. Labib; R. van Hasselt; W.S. Stevens; R. Schuurman; A.M.J. Wensing; M. van Vugt; T.F. Rinke de Wit

    2010-01-01

    Objective: To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008. Methods: Population sequencing of the HIV-1 pol gene was performed in the PharmAccess Af

  8. In Vivo and in Vitro Studies on the Localisation and Kinetics of Porphyrin Related Drugs for Photodetection and Photodynamic Therapy

    NARCIS (Netherlands)

    J.T.H.M. van den Akker (Johanna)

    2003-01-01

    textabstractPhotodetection and photodynamic therapy (PDT) of malignant and premalignant skin lesions are based on the activation of a photosensitive drug (photosensitiser) with (laser) light. The ideal photosensitiser accumulates selectively in the (pre)malignant tissue. Upon illumination with light

  9. Hyperactivity--Drug Therapy/Food Additives/Allergies. A Selective Bibliography. Exceptional Child Bibliography Series No. 602.

    Science.gov (United States)

    ERIC Clearinghouse on Handicapped and Gifted Children, Reston, VA.

    The annotated bibliography on Hyperactivity--Drug Therapy/Food Additives/Allergies contains approximately 65 abstracts and associated indexing information for documents or journal articles published from 1968 to 1975 and selected from the computer files of the Council for Exceptional Children's Information Services and the Education Resources…

  10. Fifty Cases of Child Restless Syndrome Treated with the Integrated Method of Chinese Herbal Drugs and Auricular-Plaster Therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Fifty cases of child restless syndrome were treated with oral administration of Chinese traditional herbal drugs plus auricular-plaster therapy from December 1998 to November 2001, and another 47 cases were treated with oral administration of methylphenidate as controls. The result is reported as follows.

  11. Systematic review: antihypertensive drug therapy in patients of African and South Asian ethnicity.

    Science.gov (United States)

    Brewster, Lizzy M; van Montfrans, Gert A; Oehlers, Glenn P; Seedat, Yackoob K

    2016-04-01

    Despite the large differences in the epidemiology of hypertension across Europe, treatment strategies are similar for national populations of white European descent. However, hypertensive patients of African or South Asian ethnicity may require ethnic-specific approaches, as these population subgroups tend to have higher blood pressure at an earlier age that is more difficult to control, a higher occurrence of diabetes, and more target organ damage with earlier cardiovascular mortality. Therefore, we systematically reviewed the evidence on antihypertensive drug treatment in South Asian and African ethnicity patients. We used the Cochrane systematic review methodology to retrieve trials in electronic databases including CENTRAL, PubMed, and Embase from their inception through November 2015; and with handsearch. We retrieved 4596 reports that yielded 35 trials with 7 classes of antihypertensive drugs in 25,540 African ethnicity patients. Aside from the well-known blood pressure efficacy of calcium channel blockers and diuretics, with lesser effect of ACE inhibitors and beta-blockers, nebivolol was not more effective than placebo in reducing systolic blood pressure levels. Trials with morbidity and mortality outcomes indicated that lisinopril and losartan-based therapy were associated with a greater incidence of stroke and sudden death. Furthermore, 1581 reports yielded 16 randomized controlled trials with blood pressure outcomes in 1719 South Asian hypertensive patients. In contrast with the studies in African ethnicity patients, there were no significant differences in blood pressure lowering efficacy between drugs, and no trials available with mortality outcomes. In conclusion, in patients of African ethnicity, treatment initiated with ACE inhibitor or angiotensin II receptor blocker monotherapy was associated with adverse cardiovascular outcomes. We found no evidence of different efficacy of antihypertensive drugs in South Asians, but there is a need for trials

  12. Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.

    Science.gov (United States)

    So-Ngern, Apichot; Montakantikul, Preecha; Manosuthi, Weerawat

    2014-09-01

    We conducted a cross sectional study of the outpatient medical records of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in 2011 to determine the incidence of clinically significant drug interactions (CSDI). The severities of the CSDI were graded following the Micromedex" 2.0 database and the Department of Health and Human Services (DHHS) 2012 HIV treatment guidelines. Three hundred thirty-five patients (34%) had 554 episodes of CSDI. Of which 337 episodes (61%), 163 episodes (29%) and 54 episodes (10%) had grades 2, 3 and 4 severity CSDI, respectively. The CSDI were caused by protease inhibitor (PI)-based drug regimens in 79%, by efavirenz-based regimens in 34% and by nevirapine-based regimens in 10% (pgemfibrozil (n=24) and didanosine with allopurinol (n=2). The three most common grade 3 CSDI were: a PI with a statin drug except simvastatin (n=56), fenofibrate with a statin drug (n=28) and amlodipine with simvastatin (n=14). On multivariate analysis, risk factors associated with CSDI were: receiving a PI-based regimen (OR 14.44; 95% CI: 9.10-22.88), having dyslipidemia (OR 3.94; 95% CI: 1.89-8.21), having >5 items prescribed at a time (OR 1.80; 95% CI: 1.23-2.63), seeing a doctor >4 times a year (OR 1.72; 95% CI: 1.20-2.46), having hypertension (OR 0.60; 95% CI: 0.37-0.98), having a duration of receiving ART of >5 years (OR 0.46; 95% CI: 0.28-0.77) and having a CD4 count of >200 cells/mm3 (OR 0.46; 95%CI: 0.26-0.84). CSDI were common among HIV-infected patients receiving ARV in our outpatient clinic. Patients having a low CD, count, having dyslipidemia, receiving PI-based ART, having a frequent number of visits per year and having a large number of items prescribed at each visit had a greater chance of a CSDI. PMID:25417503

  13. How Do Atrial-Selective Drugs Differ From Antiarrhythmic Drugs Currently Used in the Treatment of Atrial Fibrillation?

    Directory of Open Access Journals (Sweden)

    Alexander Burashnikov

    2008-07-01

    Full Text Available Current pharmacologic strategies for the management of atrial fibrillation (AF include use of 1 sodium channel blockers, which are contraindicated in patients with coronary artery or structural heart disease because of their potent effect to slow conduction in the ventricles, 2 potassium channel blockers, which predispose to acquired long QT and Torsade de Pointes arrhythmias because of their potent effect to prolong ventricular repolarization, and 3 mixed ion channel blockers such as amiodarone, which are associated with multi-organ toxicity. Accordingly, recent studies have focused on agents that selectively affect the atria but not the ventricles. Several atrial-selective approaches have been proposed for the management of AF, including inhibition of the atrial-specific ultrarapid delayed rectified potassium current (IKur, acetylcholine-regulated inward rectifying potassium current (IK-ACh, or connexin-40 (Cx40. All three are largely exclusive to atria. Recent studies have proposed that an atrial-selective depression of sodium channel-dependent parameters with agents such as ranolazine may be an alternative approach capable of effectively suppressing AF without increasing susceptibility to ventricular arrhythmias. Clinical evidence for Cx40 modulation or IK-ACh inhibition are lacking at this time. The available data suggest that atrial-selective approaches involving a combination of INa, IKur, IKr, and, perhaps, Ito block may be more effective in the management of AF than pure IKur or INa block. The anti-AF efficacy of the atrial-selective/predominant agents appears to be similar to that of conventionally used anti-AF agents, with the major apparent difference being that the latter are associated with ventricular arrhythmogenesis and extracardiac toxicity.

  14. How Do Atrial-Selective Drugs Differ From Antiarrhythmic Drugs Currently Used in the Treatment of Atrial Fibrillation?

    Directory of Open Access Journals (Sweden)

    Charles Antzelevitch

    2008-07-01

    Full Text Available Current pharmacologic strategies for the management of atrial fibrillation (AF include use of 1 sodium channel blockers, which are contraindicated in patients with coronary artery or structural heart disease because of their potent effect to slow conduction in the ventricles, 2 potassium channel blockers, which predispose to acquired long QT and Torsade de Pointes arrhythmias because of their potent effect to prolong ventricular repolarization, and 3 mixed ion channel blockers such as amiodarone, which are associated with multi-organ toxicity. Accordingly, recent studies have focused on agents that selectively affect the atria but not the ventricles. Several atrial-selective approaches have been proposed for the management of AF, including inhibition of the atrial-specific ultrarapid delayed rectified potassium current (IKur, acetylcholine-regulated inward rectifying potassium current (IK-ACh, or connexin-40 (Cx40. All three are largely exclusive to atria. Recent studies have proposed that an atrial-selective depression of sodium channel-dependent parameters with agents such as ranolazine may be an alternative approach capable of effectively suppressing AF without increasing susceptibility to ventricular arrhythmias. Clinical evidence for Cx40 modulation or IK-ACh inhibition are lacking at this time. The available data suggest that atrial-selective approaches involving a combination of INa, IKur, IKr, and, perhaps, Ito block may be more effective in the management of AF than pure IKur or INa block. The anti-AF efficacy of the atrial-selective/predominant agents appears to be similar to that of conventionally used anti-AF agents, with the major difference being that the latter are associated with ventricular arrhythmogenesis and extracardiac toxicity.

  15. Low Non-structured Antiretroviral Therapy Interruptions in HIV-Infected Persons Who Inject Drugs Receiving Multidisciplinary Comprehensive HIV Care at an Outpatient Drug Abuse Treatment Center.

    Science.gov (United States)

    Vallecillo, Gabriel; Mojal, Sergio; Roquer, Albert; Samos, Pilar; Luque, Sonia; Martinez, Diana; Martires, Paula Karen; Torrens, Marta

    2016-05-01

    Continuous HIV treatment is necessary to ensure successful combined antiretroviral therapy (cART). The aim of this study was to evaluate the incidence of patient-initiated non-structured treatment interruptions in HIV-infected persons who inject drugs and who received a multidisciplinary comprehensive program, including medical HIV care, drug-dependence treatment and psychosocial support, at a drug outpatient addiction center. Non-structured treatment interruptions were defined as ≥30 consecutive days off cART without medical indication. During a median follow-up of 53.8 months, 37/132 (28 %) patients experienced the first non-structured treatment interruptions. The cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4-40.0). Current drug use injection ≥1/day (HR 14.77; 95 % CI 5.90-36.96) and cART naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non-structured treatment interruptions. HIV care provided at a drug addiction center is a useful strategy to sustain continuous cART, however, drug abstinence is essential for the long-term maintenance of cART. PMID:26427376

  16. Tratamento medicamentoso da osteoartrose do joelho Drug therapy in knee osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Márcia Uchôa de Rezende

    2009-02-01

    Full Text Available O tratamento clínico da osteoartrite/artrose (OA está sempre indicado e baseia-se no autocuidado feito pelo paciente e orientado pelo médico. O uso de medicamentos é complementar às medidas de emagrecimento, ganho de força, de propriocepção, de flexibilidade e de amplitude de movimento. Entre os medicamentos disponíveis para o tratamento da OA há os que são essencialmente analgésicos e que não interferem no curso da doença; bem como os anti-inflamatórios, controversos por seus efeitos colaterais e pelo seu papel na OA, porém, com propriedades analgésicas e anti-inflamatórias indiscutíveis; e, por fim, as drogas modificadoras de estrutura, que retardam a evolução da OA. As medicações ainda podem ser de uso tópico, intra-articular, oral e injetável (sistêmico. As várias apresentações de ácido hialurônico (AH mostram o poder analgésico da droga e há indícios de poder modificador de estrutura da cartilagem pela medicação. Há nível de evidência IA, para diacereína e para a glucosamina, de que retardam a evolução da OA. Mais tecnologia para diagnóstico e controle de tratamento da OA, bem como mais estudos multicêntricos são necessários para consolidar o poder do tratamento medicamentoso de outras drogas.Clinical treatment for osteoarthritis (OA is very important and is based on patient's self care and guided by the physician. Drug therapy is additional to losing weight, improving muscular strength, proprioception, flexibility and range of motion. Between the available drugs for osteoarthritis' treatment, some are basically analgesics and do not interfere on disease's progression; some are anti-inflammatory with good analgesic power but with side effects that compromise their prolonged usage; and the structure modifying drugs that slow down the progression of OA. The medications are presented in topic, oral, intra-muscular, intra-venous and intra-articular forms. The hyaluronic acid has various

  17. [Efficacy of oral drug Thrombovasim® in therapy of lower extremity deep vein thromboses].

    Science.gov (United States)

    Mishenina, S V; Madonov, P G; Kinsht, D N; Émedova, T A; Zotov, S P; Ufimtsev, M S; Leont'ev, S G

    2016-01-01

    Within the framework of the multicenter randomized placebo-controlled double-blind clinical trial "VETTER-1" the authors carried out assessment of therapeutic efficacy and safety of oral drug Thrombovasim® possessing a thrombolytic effect in comprehensive treatment of lower-extremity deep vein thrombosis (LEDVT). The clinical study comprised a total of 154 patients. All patients received standard therapy accepted in LEDVT. The patients were subdivided into 4 groups. Patients from the three study groups received Thrombovasim® at a daily dose of 1,600, 3,200, and 4,800 IU. The control group patients were given placebo. Efficacy was assessed by the results of ultrasound duplex scanning first performed before treatment commenced and then after it terminated. The relative frequency of positive dynamics according to the findings of instrumental methods of study in patients taking Thrombovasim® amounted to 0.728 and in the group of patients receiving placebo to 0.585, p=0.0031. Comparing the degree of blood flow normalization in the zone of the compromised blood flow revealed a pronounced dose-dependent effect: in patients taking the drug at a daily dose of 1,600 IU, the relative frequency of positive dynamics amounted to 0.707 corresponding to an increase in therapeutic efficacy by 21%, for a dose of 3,200 IU these parameters amounted to 0.0257 and 24% and for 4,800 IU - 0.747 and 28%, respectively. In patients taking Thrombovasim® there were no cases of negative dynamics observed. Of the patients taking Thrombovasim®, none developed undesirable or severe adverse events. Inclusion of Thrombovasim® into the composition of comprehensive therapy for LEDVT increases efficacy of treatment at the expense of a spontaneous thrombolytic effect. The most effective dose amounted to 4,800 IU daily. Thrombovasim® turned out to be an efficient and safe agent in treatment of venous thromboses. PMID:27626255

  18. Absence of antiretroviral therapy and other risk factors for morbidity and mortality in Malaysian compulsory drug detention and rehabilitation centers.

    Directory of Open Access Journals (Sweden)

    Jeannia J Fu

    Full Text Available Throughout Asia, people who use drugs are confined in facilities referred to as compulsory drug detention and rehabilitation centers. The limited transparency and accessibility of these centers has posed a significant challenge to evaluating detainees and detention conditions directly. Despite HIV being highly prevalent in this type of confined setting, direct evaluation of detainees with HIV and their access to medical care has yet to be reported in the literature.We evaluated the health status of 100 adult male detainees with HIV and their access to medical care in the two largest Malaysian compulsory drug detention and rehabilitation centers holding HIV-infected individuals.Approximately 80% of all detainees with HIV were surveyed in each detention center. Most participants reported multiple untreated medical conditions. None reported being able to access antiretroviral therapy during detention and only 9% reported receiving any HIV-related clinical assessment or care. Nearly a quarter screened positive for symptoms indicative of active tuberculosis, yet none reported having been evaluated for tuberculosis. Although 95% of participants met criteria for opioid dependence prior to detention, none reported being able to access opioid substitution therapy during detention, with 86% reporting current cravings for opioids and 87% anticipating relapsing to drug use after release. Fourteen percent of participants reported suicidal ideation over the previous two weeks.We identified a lack of access to antiretroviral therapy in two of the six compulsory drug detention and rehabilitation centers in Malaysia designated to hold HIV-infected individuals and found significant, unmet health needs among detainees with HIV. Individuals confined under such conditions are placed at considerably high risk for morbidity and mortality. Our findings underscore the urgent need for evidence-based drug policies that respect the rights of people who use drugs and seek

  19. Application of drug delivery system for boron neutron capture therapy. Basic research toward clinical application

    International Nuclear Information System (INIS)

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10B and thermal neutrons (10B+1n → 7Li+4He (α) +2.31 MeV (93.7%)/2.79 MeV (6.3%)). The resulting lithium ions and αparticles are high linear energy transfer (LET) particles which give high biological effect. Their short range in tissue (5-9 μm) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma etc, recently. Sodium borocaptate (Na210B12H11SH; BSH) and borono-phenylalanine (10BPA) are currently being used in clinical treatments. To achieve the selective delivery of boron atoms to cancer cells, drug delivery system (DDS) becomes an attractive intelligent technology as targeting and controlled release of drugs. We have firstly reported that 10B atoms delivered by immunoliposomes are cytotoxic to human pancreatic carcinoma cells (AsPC-1) after thermal neutron irradiation in vitro. The intra-tumoural injection of boronated immunoliposomes can increase the retention of 10B atoms in tumour cells, causing suppression of tumour growth in vivo following thermal neutron irradiation. We prepared polyethylene-glycol binding liposomes (PEG-liposomes) as an effective 10B carrier to obviate phagocytosis by reticuloendotherial systems. We had prepared 10BSH entrapped Water-in-Oil-in-Water (WOW) emulsion. The 10B concentration in VX-2 tumour after intra-arterial injection of 10BSH entrapped WOW emulsion was superior to the groups of 10BSH entrapped conventional Lipiodol mix emulsion. 10Boron entrapped WOW emulsion is one of the most useful for intra-arterial boron delivery carrier on BNCT to hepatocellular carcinoma. (author)

  20. DIACEREIN AS THE DRUG OF CHOICE IN THE THERAPY OF KNEE OSTEOARTHRITIS WITH SECONDARY RECURRENT SYNOVITIS

    Directory of Open Access Journals (Sweden)

    M. I. Udovika

    2016-02-01

    Full Text Available Objective: to evaluate the efficacy and tolerability of diacerein in the therapy of primary knee osteoarthritis (OA with secondary recurrent synovitis.Subjects and methods. The 3-month open-label randomized controlled trial enrolled 133 patients with OA. Group 1 consisted of 68 subjects (42 women and 26 men; mean age 54.22±4.29 years who took diacerein 100 mg/day for 3 months. Group 2 (a control group included 65 subjects (45 women and 20 men; mean age 53.50±3.27 years who received chondroitin sulfate 1000 mg/day + glucosamine sulfate 1000 mg/day and meloxicam 7.5 mg/day for 3 months too.Results and discussion. After a therapy cycle, Group 1 patients displayed a statistically significant decrease in the Lequesne index from 13.92±2.16 to 5.95±0.92 (p=0.00005; in Group 2, this index significantly reduced from 16.72±1.78 to 10.76±1.54 (p=0.001. Pain intensity on the visual analogue scale decreased significantly from 70.88±7.06 to 22.05±6.36 mm (p<0.00001 in Group 1 and from 72.46±7.02 to 39.84±6.67 mm (p<0.0004 in Group 2. A persistent analgesic effect was achieved at weeks 6 and 7 in Groups 1 and 2, respectively. The therapeutic effect was estimated as very good and good by 48 and 52% of the patients, respectively, in Group 1 and as good and moderate by 43 and 57% in Group 2. Three months after a therapy cycle effusion in the affected knee substantially increased (from 21.70±6.29 to 29.16±3.63 ml; p<0.001 in Group 2 and slightly increased (from 5.86±3.10 to 6.12±1.09 ml; p>0.05 in Group 1, which confirms the steady-state effect of diacerein. The results of the performed open-label randomized clinical trial showed marked analgesic and anti-inflammatory effect of diacerein and allow to recommend it as the drug of choice to treat knee OA with secondary recurrent synovitis.

  1. Influence of albuminuria and glomerular filtration rate on blood pressure response to antihypertensive drug therapy

    Directory of Open Access Journals (Sweden)

    John M Flack

    2008-01-01

    urinary albumin excretion and reduced eGFR.Keywords: albuminuria, glomerular filtration rate, blood pressure, antihypertensive drug therapy

  2. The pharmacokinetics of the drugs used in interventional therapy for Primary liver cancer: its current situation in research

    International Nuclear Information System (INIS)

    For recent years, embolization agents has become one of the hot points in the discussion concerning transcatheter hepatic arterial chemoembolization (TACE) for liver carcinomas. A variety of embolic agents have been developed in order to improve the therapeutic effect of TACE. The embolic agents now used in TACE include irregular particles, spherical microspheres, drug-eluting microspheres, etc. The development of embolic agents is aimed at increasing the chemotherapy drug concentration within area and reducing peripheral blood drug concentration. Therefore, the anti-tumor efficacy can be improved, while its toxicity can be reduced. This paper aims to make a comprehensive review about the pharmacokinetic features of the drugs used in various interventional therapies for liver carcinomas. (authors)

  3. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. PMID:26732509

  4. Effectiveness of group cognitive therapy about opium addict complications on attitude of adolescents with drug dependent parents

    Directory of Open Access Journals (Sweden)

    Kaveh Hojjat

    2015-12-01

    Full Text Available Background and Aim: Statistics show that 30% to 40 % of  opium addicted fathers’ children are prone to substance abuse in the future. The present study aimed at assessing the effectiveness of cognitive therapy approach  to attitude changing of adolescents with substance dependent fathers. Materials and Methods:  In this controlled. field-trail randomized study. .data collection tool was “attitude to addiction questionnaire”. The study population was all male students in the first grade of high school in Maneh - Samalghan city. . Six sessions of group cognitive therapy based on the effectiveness of drug side-effects in drug-addicted fathers’ adolescent children’s attitude were held. The above-mentioned questionnaire was filled out before and after intervention. The obtained data  was fed into SPSS software (V: 16 using. Independent t-test .and paired t-test were used for analysis and P<0.05 was taken as the significant level. Results:  There were no significant differences between the two groups in pre-test regarding their attitude about drug abuse (P=.20%. Mean score variance from pre-test to post-test in the intervention group decreased, but in the control group, it showed a slight increase. This means that the intervention reduced the positive attitude towards drugs, but the changes were not statistically significant (p=0.57. Besides, among ten factors decisive in an individual’s attitude about addiction, only group cognitive therapy  was able  to decrease mean points of an individual’s attitude about drug abuse .. Significantly (P = 0.04. Conclusion: It was found that group cognitive therapy education about opium  addict complicationsdidn`t have a significant effect on the attitude of the students with addicted fathers. Thus, a change of adolescents’ attitude requires more research.

  5. ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs.

    Science.gov (United States)

    Barresi, Vincenza; Spampinato, Giorgia; Musso, Nicolò; Trovato Salinaro, Angela; Rizzarelli, Enrico; Condorelli, Daniele Filippo

    2016-03-01

    Copper is a catalytic cofactor required for the normal function of many enzymes involved in fundamental biological processes but highly cytotoxic when in excess. Therefore its homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones. ATOX1 (antioxidant protein 1) is a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network. In the present study the Caco-2 cell line, a colon carcinoma cell line, was used as an in vitro model to evaluate if ATOX1 deficiency could affect sensitivity to experimentally induced copper dyshomeostasis. Silencing of ATOX1 increased toxicity of a short treatment with a high concentration of Cu(2+). Copper ionophores, such as 5-chloro-8-hydroxyquinoline, induced a copper-dependent cell toxicity which was significantly potentiated after ATOX1 silencing. The copper chelator TPEN (N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine) produced a form of cell toxicity that was reversed by the addition of Cu(2+). ATOX1 silencing increased Caco-2 cell sensitivity to TPEN toxicity. Our results suggest the possibility of a therapy with copper-chelating or ionophore drugs in subtypes of tumors showing specific alterations in ATOX1 expression. PMID:26784148

  6. Influence of environmental chemicals on drug therapy in humans: studies with contraceptive steroids.

    Science.gov (United States)

    Breckenridge, A M; Back, D J; Cross, K; Crawford, F; MacIver, M; Orme, M L; Rowe, P H; Smith, E

    1980-01-01

    The effects have been studied of various environmental factors on the variability in response to oral contraceptive steroid therapy in women. Ten- to thirty-fold variations in plasma concentrations of norethisterone, L-norgestrel and ethinyloestradiol have been shown in samples taken 12 h after administration of oral contraceptives in mid-menstrual cycle. Factors shown to be responsible for this variation include passage into the enterohepatic circulation, a variable first-pass effect, and changes in metabolism in the gut wall or liver due to diet, disease, smoking or administration of drugs. Phenobarbitone and the antibiotic rifampicin increase both oestrogen and progestogen metabolism in women and in experimental animals by increasing hepatic and gut wall metabolism. In animals, other antibiotics (ampicillin, neomycin and lincomycin) suppress the gut flora that normally hydrolyse steroid conjugates excreted in bile; enterohepatic circulation or oral contraceptive steroids is thus reduced and their plasma concentrations lowered by up to 90%. In the human, ampicillin has a variable but less dramatic effect on elimination of oral contraceptives. Samples of gut wall mucosa obtained from patients with coeliac disease are defective in their ability to metabolize oral contraceptives. Cigarette smokers eliminate ethinyloestradiol more rapidly than non-smokers; an increased production of reactive steroid metabolites may thus be a cause of vascular disease in women who smoke and take contraceptive steroids. PMID:6906266

  7. Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

    Directory of Open Access Journals (Sweden)

    Belsing Tina Z

    2010-09-01

    Full Text Available Abstract Context Hyperthyroidism can lead to reduced bone mineral density (BMD and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.

  8. Effects of antihyperlipidemic drugs and diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia.

    Science.gov (United States)

    Nomura, H; Kimura, Y; Okamoto, O; Shiraishi, G

    1996-01-01

    We compared the efficacy of two antihyperlipidemic drugs and the efficacy of diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia. The study included 48 patients with moderate hypercholesterolemia (serum total cholesterol [TC], 250 to 320 mg/dL). Patients were divided into three groups: group A--patients administered 10 mg/d of pravastatin; group B--patients administered 500 mg/d of probucol and 600 mg/d of pantethine; and group C--patients administered diet plus exercise therapy. The serum TC and serum high-density lipoprotein cholesterol (HDL-C) values were determined via enzymatic methods before initiation of each therapy and after 4 and 8 weeks of therapy. An atherogenic index (AI) was also calculated. The results indicated that TC showed a statistically significant decrease in all three groups at 4 and 8 weeks (P < 0.001 and P < 0.05, respectively); the HDL-C value did not change significantly in groups A and C, but it had a statistically significant decrease in group B at 4 and 8 weeks. The AI showed a statistically significant decrease in group A at 4 and 8 weeks of treatment and group C at 8 weeks; there were no significant changes in AI in group B. It may be concluded that as an antihyperlipidemic agent, pravastatin is more useful than probucol and that appropriate exercise and strict dietary management for 8 weeks achieve an efficacy close to that achieved by drug therapy. PMID:8829023

  9. Adjuncts to opioid therapy.

    Science.gov (United States)

    Goldstein, Frederick J

    2002-09-01

    Administration of opioids to alleviate moderate to severe acute pain and chronic cancer pain is an established management process. However, advancements in clinical pharmacologic research have shown that opioids are also effective in chronic noncancerous pain. Many patients properly treated for prolonged periods with opioids develop tolerance and subsequently, physical dependence. This process is not necessarily harmful to the patient and will not cause the patient to develop an addiction (properly defined as psychologic dependence). For many patients who have been on opioid therapy for months or years, analgesic effectiveness tragically becomes less. In addition, opioid-induced constipation can be severe and cause pain; patients do not develop tolerance to this adverse reaction. Therefore, such issues become a management problem and require additional intervention. Currently, many different classes of drugs can serve as effective adjuncts to opioids for treatment of pain. Adding adjunctive medication to opioid therapy improves pain management primarily by nonopioid mechanisms of action. Clinical outcomes of such combinations include greater analgesia and attenuation of opioid-induced adverse reactions such as nausea and vomiting, constipation, sedation, and respiratory depression. Adjuncts include acetaminophen, antiarrhythmics, anticonvulsants, antidepressants, antipsychotics, baclofen, benzodiazepines, capsaicin, calcium channel blockers, clonidine hydrochloride, central nervous system stimulants, corticosteroids, local anesthetics, N-methyl-D-aspartate receptor antagonists, nonsteroidal antiinflammatory drugs, pentoxifylline, and scopolamine. Some adjuncts (eg, acetaminophen) are routinely used today, whereas others (eg, nifedipine [calcium channel blocker]) are used on a limited basis but have great potential for more widespread application. All professionals (eg, nurses, pharmacists, physicians, physicians' assistants, social workers, members of the clergy

  10. A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy.

    Science.gov (United States)

    Qiu, Liping; Chen, Tao; Öçsoy, Ismail; Yasun, Emir; Wu, Cuichen; Zhu, Guizhi; You, Mingxu; Han, Da; Jiang, Jianhui; Yu, Ruqin; Tan, Weihong

    2015-01-14

    The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver-gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells. PMID:25479133

  11. A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

    Science.gov (United States)

    Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

    2016-05-28

    Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. PMID:27040815

  12. Are the effects of a non-drug multimodal activation therapy of dementia sustainable? Follow-up study 10 months after completion of a randomised controlled trial

    OpenAIRE

    Luttenberger Katharina; Hofner Benjamin; Graessel Elmar

    2012-01-01

    Abstract Background Little is known about the long-term success of non-drug therapies for treating dementia, especially whether the effects are sustained after therapy ends. Here, we examined the effects of a one-year multimodal therapy 10 months after patients completed the therapy. Methods This randomised, controlled, single-blind, longitudinal trial involved 61 patients (catamnesis: n = 52) with primary degenerative dementia in five nursing homes in Bavaria, Germany. The highly standardise...

  13. Factors linked to transitions in adherence to antiretroviral therapy among HIV-infected illicit drug users in a Canadian setting

    OpenAIRE

    Joseph, Brenden; Kerr, Thomas; Puskas, Cathy M; Montaner, Julio; Wood, Evan; Milloy, M-J

    2015-01-01

    HIV-positive people who use illicit drugs typically achieve lower levels of adherence to antiretroviral therapy and experience higher rates of sub-optimal HIV/AIDS treatment outcomes. Given the dearth of longitudinal research into ART adherence dynamics, we sought to identify factors associated with transitioning into and out of optimal adherence to ART in a longitudinal study of HIV-infected people who use illicit drugs (PWUD) in a setting of universal no-cost HIV/AIDS treatment. Using data ...

  14. Access to highly active antiretroviral therapy (HAART) for injecting drug users in the WHO European Region 2002-2004

    DEFF Research Database (Denmark)

    Donoghoe, Martin C; Bollerup, Annemarie R; Lazarus, Jeff;

    2007-01-01

    Providing equitable access to highly active antiretroviral treatment (HAART) to injecting drug users (IDUs) is both feasible and desirable. Given the evidence that IDUs can adhere to HAART as well as non-IDUs and the imperative to provide universal and equitable access to HIV/AIDS treatment for all...... injecting status of those initiating HAART and the use of opioid substitution therapy among HAART patients, and discuss how HAART might be better delivered to injecting drug users. Our data adds to the evidence that IDUs in Europe have poor and inequitable access to HAART, with only a relatively small...

  15. Exploiting Drug Repositioning for Discovery of a Novel HIV Combination Therapy

    OpenAIRE

    Clouser, Christine L.; Patterson, Steven E.; Louis M Mansky

    2010-01-01

    The development of HIV drugs is an expensive and a lengthy process. In this study, we used drug repositioning, a process whereby a drug approved to treat one condition is used to treat a different condition, to identify clinically approved drugs that have anti-HIV activity. The data presented here show that a combination of two clinically approved drugs, decitabine and gemcitabine, reduced HIV infectivity by 73% at concentrations that had minimal antiviral activity when used individually. Dec...

  16. Long-Term Drug Survival of TNF Inhibitor Therapy in RA Patients: A Systematic Review of European National Drug Registers

    Directory of Open Access Journals (Sweden)

    Anamika Arora

    2013-01-01

    Full Text Available Objective. The present systematic review of RA registry data was undertaken to analyse the time on treatment of licensed TNF inhibitors in patients with RA in Europe. Methods. English language European registry studies comparing TNF inhibitors were searched using MEDLINE, Embase, Cochrane, and WHO: ICTRP up to 16 April 2012 and proceedings of three selected conferences held between 2010 and 2012. Pooled analysis was performed to determine drug survival rates for each TNF inhibitor. Results. Sixteen studies met the inclusion criteria, of which 11 studies assessed biologic-naive patients and five studies included a mixed population of biologic-naive and biologic pretreated patients. The overall effectiveness of TNF inhibitors diminished with time, leading to decreased drug survival rates. Pooled drug survival rates after 60 months follow-up were 37% (infliximab, 48% (adalimumab, and 52% (etanercept. Further, in an observational study, when TNF inhibitors were used in combination with methotrexate, a longer drug survival was observed compared to TNF inhibitors alone. Conclusion. The findings of this systematic review indicated numerically lower drug discontinuation rates with etanercept than adalimumab, whereas infliximab had the highest rate. Further research is needed to understand the underlying mechanisms of treatment discontinuation with TNF inhibitors.

  17. 失眠症的非药物治疗进展①%Advance in Non-drug Therapy of Insomnia (review)

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    At present, insomnia treatments mainly contain drug therapy and non-drug therapy. The non-drug therapy included sleep hy-giene instruction, cognitive behavioral therapy, psychological therapy, physical therapy, relaxation therapy, and music therapy, etc. The non-drug therapy is a safe and effective treatment, and it plays a good effect whether using with drug or alone.%  目前关于失眠症的治疗方法主要有药物治疗和非药物治疗。非药物治疗有睡眠卫生指导、认知行为治疗、心理疗法、物理疗法、松弛疗法、音乐疗法等。非药物治疗具有安全有效的优势,无论是与药物联合还是单独运用均起到较好的效果。

  18. 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

    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...... here report the efficacy of everolimus treatment of patients with AIH. MATERIALS AND METHODS: Seven patients (six female, mean age 47 years, range 22-62 years) in whom disease control could not be achieved with standard therapy or the alternative drugs in use were included. RESULTS: Treatment with...... everolimus induced a clear reduction of transaminases within 2 weeks. After 3-5 months three patients had normal alanineaminotransferase (ALT) levels (10-45 IU) and four patients had ALT levels below 55 IU compared to a three- to fivefold elevated level prior to everolimus treatment. Sustained remission...

  19. Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies.

    Science.gov (United States)

    Bauer, Renato A

    2015-09-01

    Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects achievable with covalent drugs may result in less-frequent drug dosing and in wide therapeutic margins for patients. Covalent inhibition can also dissociate drug pharmacodynamics (PD) from pharmacokinetics (PK), which can result in desired drug efficacy for inhibitors that have short systemic exposure. Evidence suggests that there is a reduced risk for the development of resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious disease. PMID:26002380

  20. Radioiodine therapy of Graves' disease - a dosimetric comparison of different strategies concerning antithyroid drugs

    International Nuclear Information System (INIS)

    Aim: Premedication with antithyroid drugs (ATD) compared to patients not pretreated with ATD causes a higher failure rate of radioiodine therapy (RITh) or demands higher therapeutical dosage of radioiodine (RI). For clinical reasons and because of accelerated iodine metabolism in hyperthyreosis a compensated thyroid metabolism is desirable. Aim of this study was to investigate the influence of ATD on the biokinetics of RI in case of Graves' disease in order to improve RITh of patients pre-treated with ATD. Methods: 385 consecutive patients who underwent RITh because of Graves' disease for the first time were included: Group A (n = 74): RITh under continuous medication with ATD; Group B (n = 111): Application of RI under continuous medication with ATD, in case of insufficient RI-uptake or shortened effective RI-half-life ATD were stopped 1-5 days after RITh; Group C (n = 200): ATD were stopped 2 days prior to RITh in all patients. We examined the influence of ATD on RI-uptake and effective RI-half-life as well as the absorbed dose achieved on the thyroid in dependence of thyroid volume and applied RI-dosage [TEQ - therapy efficiency quotient, (2)]. Results: In the RI-pretest (all patients under ATD) the RI-uptake was comparable in all three groups. During RITh-RI-uptake, effective RI-half-life and therefore the TEQ were significantly higher in Group C as compared to Groups A and B (p<0,001, respectively). In Group B the medication with ATD was stopped in 61 of 111 cases 1-5 days after RITh. In this subgroup the effective RI-half-life increased from 4,4 ± 1,7 d to 5,1 ± 1,6 d after stopping of ATD (p = 0,001). Conclusion: Stopping of ATD 2 days prior to RITh leads to an increased efficiency of about 50% compared to RITh carried out under ATD and therefore to a clear reduction of radiation exposure to the rest of the body with equal absorbed doses of the thyroid. Stopping of ATD shortly after RITh increases efficiency in case of short effective RI-half-life, but it

  1. [Food allergies. III. Therapy: elimination diet, symptomatic drug prophylaxis and specific hyposensitization].

    Science.gov (United States)

    Wüthrich, B; Hofer, T

    1986-10-11

    The treatment of food allergies is logically based on strict elimination of causative allergens. While it is easy to eliminate food which is infrequently consumed, it is more difficult to manage an allergy involving regularly consumed foods, especially where patients have to eat away from home for professional reasons. The creation of elimination diets for milk, eggs, and mould and yeast allergies is discussed. In raw food and vegetable allergy the act of cooking is often sufficient to denature the allergen as it is unstable to heat. Follow-up investigations show that some 50% of children achieve cure spontaneously by strict elimination diet, especially in regard to milk allergy. In our own 173 (mainly adult) patients with food allergy, some 2/3 reported after 3-5 years that a strict elimination diet had to be followed, since otherwise prompt relapse of allergic symptoms was noted. About 1/3 of patients, mainly with milk, cheese or egg allergy, can hope for spontaneous desensitization by appropriate diet. This is demonstrated by a case history with disappearance of IgE antibodies. Should this fail to occur, oral desensitization with milk or egg-white extracts offers an effective therapy. The practice of hyposensitization with foodstuffs is illustrated by examples and tabulation of immunologic parameters. In raw food or vegetable allergy, which is often associated with birch or mugwort pollinosis, improvement or even complete cure can be expected in about 1/3 of cases by systematic desensitization of pollinosis. On the other hand, the therapy and prognosis of food allergy involving extreme and polyvalent sensitivities, especially to spices, or with multifactorially induced symptoms, is more problematic. In these cases a strict elimination diet should be followed by continuous prophylactic/symptomatic treatment with antianaphylactic substances such as cromoglicinic acid (Nalcrom) - especially in gastrointestinal food allergies - or with ketotifen (Zaditen) or

  2. Small-Molecule Inhibition of HIV pre-mRNA Splicing as a Novel Antiretroviral Therapy to Overcome Drug Resistance

    OpenAIRE

    Nadia Bakkour; Yea-Lih Lin; Sophie Maire; Lilia Ayadi; Florence Mahuteau-Betzer; Chi Hung Nguyen; Clément Mettling; Pierre Portales; David Grierson; Benoit Chabot; Philippe Jeanteur; Christiane Branlant; Pierre Corbeau; Jamal Tazi

    2007-01-01

    Author Summary Over the two decades highly active antiretroviral therapy (HAART) for the treatment of HIV infection has led to a significant decline in morbidity and mortality rates among HIV-infected individuals. HAART uses a combination of molecules that target the virus itself. However, naturally occurring and extensive genetic variation found in the virus allow the emergence of drug-resistant viruses, which rapidly render individuals untreatable. An alternative approach for effective anti...

  3. Statistical issues in multisite effectiveness trials: the case of brief strategic family therapy for adolescent drug abuse treatment

    OpenAIRE

    Feaster, Daniel J.; Robbins, Michael S.; Horigian, Viviana; Szapocznik, José

    2004-01-01

    The statistical development of the multisite Brief Strategic Family Therapy (BSFT) Trial of the National Institute on Drug Abuse’s Clinical Trials Network provides a useful, real example of how an effectiveness trial can differ from an efficacy trial. In particular, two design elements distinguish this effectiveness trial from an efficacy trial. First, because the goal of the trial is to show that the use of BSFT would be an improvement on current practice, it was decided to compare BSFT to t...

  4. Adverse drug reactions to antiretroviral therapy: Results from spontaneous reporting system in Nigeria

    Directory of Open Access Journals (Sweden)

    Kenneth A Agu

    2013-01-01

    Full Text Available Aim: This study evaluated the suspected adverse drug reactions (ADR reported from a spontaneous reporting program in Human Immunodeficiency Virus (HIV positive patients receiving antiretroviral therapy (ART in Nigeria Materials and Methods: This descriptive study analyzed individual case safety reports (ICSRs in HIV-positive patients receiving ART between January 2011 and December 2011 in 38 secondary hospitals. All ICSRs during this period were included. Chi-square was used to test the association between variables at 95% confidence interval. Results: From 1237 ICSRs collated, only 1119 (90.5% were valid for analysis. Mean age of patients was 35.3 (95%CI, 35.1-35.5 years; and 67.1% were females. A total of 1679 ADR cases were reported, a mean (± Standard Deviation, SD of 1.5 (± 0.8 ADR cases per patient. Of reported ADRs, 63.2%, 8.2% and 19.3% occurred in patients on Zidovudine-based, Stavudine-based and Tenofovir-based regimens, respectively. The commonest ADRs included (12.0% peripheral neuropathy, (11.4% skin rash, (10.1% pruritus and (6.5% dizziness. ADR occurrence was associated with ART regimens, concomitant medicines and age (P < 0.05 unlike gender. Anaemia was associated with Zidovudine (AZT/ Lamivudine (3TC /Nevirapine (NEV regimen [Odds ratio, OR = 6.4 (3.0-13.8; P < 0.0001], and peripheral neuropathy with Stavudine (d4T/3TC/NEV regimen [OR = 8.7 (5.8-30.0, P < 0.0001] and Tenofovir (TDF/Emtricitabine (FTC/Efavirenz (EFV regimen [OR = 2.1 (1.0-4.1, P = 0.0446]. Skin rash and peripheral neuropathy were associated with patients aged < 15years [OR = 3.0 (1.3-6.6, P = 0.0056] and 45-59years [OR = 1.9 (1.3-2.7, P = 0.0006] respectively. Palpitation and polyuria were associated with Salbutamol [OR = 55.7 (4.9-349.6, P = 0.0000] and Nonsteroidal anti-inflammatory drugs (NSAIDS [OR = 50.2 (0.9-562.1, P = 0.0040] respectively. Conclusion: ADRs were less likely to occur in patients on stavudine-based and tenofovir-based regimens compared to

  5. Metabolic Syndromes Associated with HIV: Mitigating the Side Effects of Drug Therapy.

    Science.gov (United States)

    Stringer, William W.; Sattler, Fred R.

    2001-01-01

    HIV infection and highly active antiretroviral therapy (HAART) are associated with such metabolic disorders as AIDS wasting syndrome, metabolic dysregulation, and abnormalities of serum lipids. Adjunctive therapies (e.g., diet and antilipid therapy); risk factor modification (e.g., smoking cessation and blood pressure control); aerobic exercise;…

  6. Commercialization strategy of the herbal composition HemoHIM as a complementary drug for anti-cancer therapies

    International Nuclear Information System (INIS)

    Ο Purpose - Establishment of strategy for the development of HemoHIM as a complementary drug for cancer therapies including non-clinical data preparation, obtainment of a research project grant, base of manufacturing process and raw material standardization Ο Research Results - Examination and confirmation of the essential requirements to develop the complementary drug for anticancer therapies by consulting with Korea FDA, and clinical CRO, and medical experts (animal efficacy study, toxicological safety test, standard analytical method, raw material standardization) - Obtainment of a governmental research project for 3 years from Ministry of Health and Welfare to develop HemoHIM as an complementary herbal drug for anti-cancer therapies - Acquisition of fundamental data on the manufacturing process and the raw material standardization for the optimal efficacy of HemoHIM Ο Expected benefit - Planning to get the approval of IND from Korea FDA by 2015 after completing the non-clinical study through the on-going project from Ministry of Health and Welfare - Planning to commercialize the product by 2017

  7. Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

    Directory of Open Access Journals (Sweden)

    Nadia Bakkour

    2007-10-01

    Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

  8. Commercialization strategy of the herbal composition HemoHIM as a complementary drug for anti-cancer therapies

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sungkee; Jung, Uhee; Park, Haeran

    2013-01-15

    Ο Purpose - Establishment of strategy for the development of HemoHIM as a complementary drug for cancer therapies including non-clinical data preparation, obtainment of a research project grant, base of manufacturing process and raw material standardization Ο Research Results - Examination and confirmation of the essential requirements to develop the complementary drug for anticancer therapies by consulting with Korea FDA, and clinical CRO, and medical experts (animal efficacy study, toxicological safety test, standard analytical method, raw material standardization) - Obtainment of a governmental research project for 3 years from Ministry of Health and Welfare to develop HemoHIM as an complementary herbal drug for anti-cancer therapies - Acquisition of fundamental data on the manufacturing process and the raw material standardization for the optimal efficacy of HemoHIM Ο Expected benefit - Planning to get the approval of IND from Korea FDA by 2015 after completing the non-clinical study through the on-going project from Ministry of Health and Welfare - Planning to commercialize the product by 2017.

  9. Modeling of pharmacokinetics of cocaine in human reveals the feasibility for development of enzyme therapies for drugs of abuse.

    Directory of Open Access Journals (Sweden)

    Fang Zheng

    Full Text Available A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emission tomography data in human to examine the effects of a cocaine-metabolizing enzyme in plasma on the time course of cocaine in plasma and brain of human. Without an exogenous enzyme, cocaine half-lives in both brain and plasma are almost linearly dependent on the initial cocaine concentration in plasma. The threshold concentration of cocaine in brain required to produce physiological effects has been estimated to be 0.22±0.07 µM, and the threshold area under the cocaine concentration versus time curve (AUC value in brain (denoted by AUC2(∞ required to produce physiological effects has been estimated to be 7.9±2.7 µM·min. It has been demonstrated that administration of a cocaine hydrolase/esterase (CocH/CocE can considerably decrease the cocaine half-lives in both brain and plasma, the peak cocaine concentration in brain, and the AUC2(∞. The estimated maximum cocaine plasma concentration which a given concentration of drug-metabolizing enzyme can effectively prevent from entering brain and producing physiological effects can be used to guide future preclinical/clinical studies on cocaine-metabolizing enzymes. Understanding of drug-metabolizing enzymes is key to the science of pharmacokinetics. The general insights into the effects of a drug-metabolizing enzyme on drug kinetics in human should be valuable also in future development of enzyme therapies for other drugs of abuse.

  10. Study on liposomalization of zinc-coproporphyrin I as a novel drug in photodynamic therapy.

    Science.gov (United States)

    Sadzuka, Yasuyuki; Iwasaki, Fumiaki; Sugiyama, Ikumi; Horiuchi, Kentaro; Hirano, Toru; Ozawa, Hidechika; Kanayama, Naohiro; Sonobe, Takashi

    2007-06-29

    Photodynamic therapy (PDT) with a photosensitizer and laser irradiation has been shown to have potential effects in cancer chemotherapy. However, the commercial drug clinically gave many problems due to the poor solubility of the photosensitizer in water and the photosensitivity as an adverse reaction of PDT. We have examined best condition on the liposomalization of Zn-complexed coproporphyrin I (ZnCPI) as novel photosensitizer. The difference of pH in buffer significantly changed the ZnCPI entrapped ratio. The entrapped ratio of ZnCPI in PBS(-) buffer was 10.8+/-0.3%, whereas, these levels in some lactate buffer (below pH 5.0) increased. The change between the molecular formionic form of ZnCPI was occurred due to the change of the pH of buffer, and the amount of ZnCPI in the liposomal membrane changed. The difference of this level was considered to be contributed by the change of zeta potentials. Next, we examined the effect of the different pH of the buffer in liposomal preparation on the ZnCPI distribution in each tissue after each liposome administration. At 2 and 6h post-injection of ZnCPI liposome (pH 4.6), the ZnCPI concentration in the plasma of Ehrlich ascites carcinoma bearing mice was shown to be higher compared to that in other groups. The ZnCPI concentrations in the tumor after 2 and 6h of ZnCPI liposome (pH 4.6) treatment were shown to be higher than that in other groups. In conclusion, it is considered that the ZnCPI liposome (pH 4.6) had the effective antitumor activity with laser irradiation without the adverse reactions. PMID:17349754

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

    Science.gov (United States)

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

    2016-01-01

    Background: 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. Methods: 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. Results: 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. Conclusion: According to Iranian traditional medicine and latest articles, dalk as a non-drug therapy and prevention manner is recommended. PMID:27516677

  12. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong, E-mail: Zheng-qx@163.co [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2009-12-15

    In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

  13. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

    International Nuclear Information System (INIS)

    In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

  14. Management of HIV/AIDS in older patients–drug/drug interactions and adherence to antiretroviral therapy

    OpenAIRE

    Burgess, Mary

    2015-01-01

    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 ha...

  15. Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy.

    Science.gov (United States)

    Kim, Hyun-Yi; Choi, Sehee; Yoon, Ji-Hye; Lim, Hwan Jung; Lee, Hyuk; Choi, Jiwon; Ro, Eun Ji; Heo, Jung-Nyoung; Lee, Weontae; No, Kyoung Tai; Choi, Kang-Yell

    2016-01-01

    Bone anabolic agents promoting bone formation and rebuilding damaged bones would ideally overcome the limitations of anti-resorptive therapy, the current standard prescription for osteoporosis. However, the currently prescribed parathyroid hormone (PTH)-based anabolic drugs present limitations and adverse effects including osteosarcoma during long-term use. Also, the antibody-based anabolic drugs that are currently being developed present the potential limits in clinical application typical of macromolecule drugs. We previously identified that CXXC5 is a negative feedback regulator of the Wnt/β-catenin pathway via its interaction with Dishevelled (Dvl) and suggested the Dvl-CXXC5 interaction as a potential target for anabolic therapy of osteoporosis. Here, we screened small-molecule inhibitors of the Dvl-CXXC5 interaction via a newly established in vitro assay system. The screened compounds were found to activate the Wnt/β-catenin pathway and enhance osteoblast differentiation in primary osteoblasts. The bone anabolic effects of the compounds were shown using ex vivo-cultured calvaria. Nuclear magnetic resonance (NMR) titration analysis confirmed interaction between Dvl PDZ domain and KY-02061, a representative of the screened compounds. Oral administration of KY-02327, one of 55 newly synthesized KY-02061 analogs, successfully rescued bone loss in the ovariectomized (OVX) mouse model. In conclusion, small-molecule inhibitors of the Dvl-CXXC5 interaction that block negative feedback regulation of Wnt/β-catenin signaling are potential candidates for the development of bone anabolic anti-osteoporosis drugs. PMID:26941261

  16. Doxorubicin loaded pH-responsive micelles capable of rapid intracellular drug release for potential tumor therapy.

    Science.gov (United States)

    Li, Shuai; Wu, Wei; Xiu, Kemao; Xu, Fujian; Li, Zhongming; Li, Jianshu

    2014-08-01

    Amphiphilic copolymers have been paid much attention for controlled drug release for many years due to their obvious advantages. In this study, an acid-triggered drug carrier system capable of rapid intracellular drug release is investigated for potential tumor therapy. The amphiphilic diblock copolymer poly(2-diisopropylaminoethyl methacrylate)-b-poly(2-aminoethyl methacrylate hydrochloride) (PDPA-b-PAMA) is prepared by atom transfer radical polymerization (ATRP). The molecular structure of the copolymer is confirmed by 1H NMR and gel permeation chromatography (GPC). The critical micelle concentration (CMC) value of the PDPA-b-PAMA is 0.005 mg/mL, which can ensure the thermodynamical stability of micelles even after significant dilution. The drug loading and encapsulation efficiencies of doxorubicin (DOX)-loaded micelles are 9.96% and 55.31%, respectively. Dynamic light scattering (DLS) and transmission electron microscope (TEM) show that the amphiphilic block copolymers self-assemble into spherical micelles with narrow polydispersity indexes (PDLs) at pH 7.4 and 6.8, but disassemble into random chain aggregations at pH 5.0. The DOX-loaded PDPA-b-PAMA shows obvious pH-responsive drug release profile when the pH value changes from 7.4 to 5.0, since it transforms from amphiphilicity to double hydrophilicity through the protonation of PDPA block (pK(a) - 6.2) in a relatively low pH condition, thus the loaded DOX can be rapidly released from the disassembling micelles. In addition, the micellar system also exhibits relatively low cytotoxicity and rapid drug release behaviour in tumor cells, which make it promising for tumor therapy. PMID:25016648

  17. Studies of Retroviral Reverse Transcriptase and Flaviviral Protease Enzymes as Antiviral Drug Targets : Applications in Antiviral Drug Discovery & Therapy

    OpenAIRE

    Junaid, Muhammad

    2012-01-01

    Viruses are a major threat to humans due to their unique adaptability, evolvability and  capability to control their hosts as parasites and genetic elements. HIV/AIDS is the third largest cause of death by infectious diseases in the world, and drug resistance due to the viral mutations is still the leading cause of treatment failure. The flaviviruses, such as Dengue virus (DEN) and Japanese encephalitis virus (JEV), represent other major cause of morbidity and mortality, and the areas where t...

  18. Long-Term Drug Survival of TNF Inhibitor Therapy in RA Patients: A Systematic Review of European National Drug Registers

    OpenAIRE

    Arora, Anamika; Mahajan, Anadi; Spurden, Dean; Boyd, Helen; Porter, Duncan

    2013-01-01

    Objective. The present systematic review of RA registry data was undertaken to analyse the time on treatment of licensed TNF inhibitors in patients with RA in Europe. Methods. English language European registry studies comparing TNF inhibitors were searched using MEDLINE, Embase, Cochrane, and WHO: ICTRP up to 16 April 2012 and proceedings of three selected conferences held between 2010 and 2012. Pooled analysis was performed to determine drug survival rates for each TNF inhibitor. Results. S...

  19. Tumor-Homing and Penetrating Peptide-Functionalized Photosensitizer-Conjugated PEG-PLA Nanoparticles for Chemo-Photodynamic Combination Therapy of Drug-Resistant Cancer.

    Science.gov (United States)

    Feng, Xingye; Jiang, Di; Kang, Ting; Yao, Jianhui; Jing, Yixian; Jiang, Tianze; Feng, Jingxian; Zhu, Qianqian; Song, Qingxiang; Dong, Nan; Gao, Xiaoling; Chen, Jun

    2016-07-20

    The combination of photodynamic therapy (PDT) and chemotherapy holds great potential in combating drug-resistant cancers. However, the major challenge that lies ahead is how to achieve high coloading capacity for both photosensitizer and chemo-drugs and how to gain efficient delivery of drugs to the drug-resistant tumors. In this study, we prepared a nanovehicle for codelivery of photosensitizer (pyropheophorbide-a, PPa) and chemo-drugs (paclitaxel, PTX) based on the synthesis of PPa-conjugated amphiphilic copolymer PPa-PLA-PEG-PLA-PPa. The obtained nanoparticles (PP NP) exhibited a satisfactory high drug-loading capacity for both drugs. To achieve effective tumor-targeting therapy, the surface of PP NP was decorated with a tumor-homing and penetrating peptide F3. In vitro cellular experiments showed that F3-functionalized PP NP (F3-PP NP) exhibited higher cellular association than PP NP and resulted in the strongest antiproliferation effect. In addition, compared with the unmodified nanoparticles, F3-PP NP exhibited a more preferential enrichment at the tumor site. Pharmacodynamics evaluation in vivo demonstrated that a longer survival time was achieved by the tumor-bearing mice treated with PP NP (+laser) than those treated with chemotherapy only or PDT only. Such antitumor efficacy of combination therapy was further improved following the F3 peptide functionalization. Collectively, these results suggested that targeted combination therapy may pave a promising way for the therapy of drug-resistant tumor. PMID:27332148

  20. Digoxin Therapy of Fetal Superior Ventricular Tachycardia: Are Digoxin Serum Levels Reliable?

    Science.gov (United States)

    Saad, Antonio F.; Monsivais, Luis; Pacheco, Luis D.

    2016-01-01

    Background  Despite its seldom occurrence, fetal tachycardia can lead to poor fetal outcomes including hydrops and fetal death. Management can be challenging and result in maternal adverse effects secondary to high serum drug levels required to achieve effective transplacental antiarrhythmic drug therapy. Case  A 33-year-old woman at 33 weeks of gestation with a diagnosis of a fetal sustained superior ventricular tachycardia developed chest pain, shortness of breath, and bigeminy on electrocardiogram secondary to digoxin toxicity despite subtherapeutic serum drug levels. She required supportive care with repletion of corresponding electrolyte abnormalities. After resolution of cardiac manifestations of digoxin toxicity, the patient was discharged home. The newborn was discharged at day 9 of life on maintenance amiodarone. Conclusion  We describe an interesting case of digoxin toxicity with cardiac manifestations of digoxin toxicity despite subtherapeutic serum drug levels. This case report emphasizes the significance of instituting an early diagnosis of digoxin toxicity during pregnancy, based not only on serum drug levels but also on clinical presentation. In cases of refractory supportive care, digoxin Fab fragment antibody administration should be considered. With timely diagnosis and treatment, excellent maternal and perinatal outcomes can be achieved.

  1. Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

    Science.gov (United States)

    Kambalapally, Swetha Reddy

    The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as

  2. Drug: D01182 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01182 Drug Alprenolol hydrochloride (JP16/USAN); Regletin (TN) C15H23NO2. HCl 285....1496 285.8096 D01182.gif Anti-adrenergic [beta-receptor] Therapeutic category: 2123 ATC code: C07AA01 beta1-adr...energic receptor antagonist [HSA:153] [KO:K04141]; beta2-adrenergic receptor antagonist [HSA:154] [KO:K04142]; beta3-adr...+155) Calcium signaling pathway hsa04080(153+154+155) Neuroactive ligand-receptor interaction hsa04261(153+154) Adr...] map07037 Antiarrhythmic drugs map07214 beta-Adrenergic receptor agonists/antago

  3. Drug: D02088 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02088 Drug Tocainide hydrochloride (USP); Tonocard (TN) C11H16N2O. HCl 228.1029 22...el (SCN9A) blocker [HSA:6335] [KO:K04841] map07037 Antiarrhythmic drugs map07231 ...3 Tocainide D02088 Tocainide hydrochloride (USP) Target-based classification of dr...dium channel (SCN1A) [HSA:6323] [KO:K04833] Tocainide [ATC:C01BB03] D02088 Tocainide hydrochloride (USP) vol...tage-gated sodium channel (SCN2A) [HSA:6326] [KO:K04834] Tocainide [ATC:C01BB03] D02088 Tocainide hydrochlor

  4. Drug: D02389 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02389 Drug Primidolol (USAN/INN) C17H23N3O4 333.1689 333.3822 D02389.gif Antihyper...tensive; Anti-anginal; Cardiac depressant [anti-arrhythmic] Same as: C11774 beta1-adrenergic receptor antago...nist [HSA:153] [KO:K04141]; beta2-adrenergic receptor antagonist [HSA:154] [KO:K04142]; beta3-adrenergic rec...thway hsa04080(153+154+155) Neuroactive ligand-receptor interaction hsa04261(153+154) Adrenergic signaling i...n cardiomyocytes hsa04970(153+154+155) Salivary secretion Target-based classification of drugs [BR:br08310

  5. Drug Carrier in der systemischen und lokoregionären Therapie - Eine Studie zum Anreicherungsverhalten von Taxol® in der systemischen und lokoregionären Therapie des CC 531- Lebertumors der Ratte

    OpenAIRE

    Ülker, Gültan

    2010-01-01

    An animal-experimental study to the enrichment behaviour of Paclitaxel in systemic and lokoregional therapy of the CC 531-of liver tumour of the rat. The lokoregional therapy should cause a high selective enrichment of the therapeutic in the tumour and therefore higher drug concentration reach with as low as possible systemic pollution. We have called the combination of the regional embolization by means of degradable starch microspheres and the drug targeting by the lokoregional applicatio...

  6. An imaging-guided platform for synergistic photodynamic/photothermal/chemo-therapy with pH/temperature-responsive drug release.

    Science.gov (United States)

    Lv, Ruichan; Yang, Piaoping; He, Fei; Gai, Shili; Yang, Guixin; Dai, Yunlu; Hou, Zhiyao; Lin, Jun

    2015-09-01

    To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating photosensitive Au25(SR)18 - (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug (doxorubicin, DOX) onto the surface of mesoporous silica coated core-shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light. PMID:26093792

  7. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    Science.gov (United States)

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. PMID:26461922

  8. Cancer therapy disparity: unequal access to breast cancer therapeutics and drug funding in Canada

    OpenAIRE

    Verma, S.; Sehdev, S.; Joy, A.A.

    2007-01-01

    Adjuvant therapy has made a significant contribution in reducing breast cancer–specific mortality. Standard chemotherapeutics and tamoxifen have been the mainstay treatment for years, but recent clinical evidence supports the use of novel small-molecule therapy and aromatase inhibitor therapy in selected settings, challenging not only the traditional paradigm of breast cancer treatment, but also provincial funding of oncologic care across Canada. The disparity in access to aromatase inhibitor...

  9. Stimuli-free programmable drug release for combination chemo-therapy

    Science.gov (United States)

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

    2016-06-01

    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

  10. Local delivery of photosensitizing drugs in arteries: a novel approach to photodynamic therapy for the prevention of intimal hyperplasia

    Science.gov (United States)

    Adili, Farzin; van Eps, Randolph G.; LaMuraglia, Glenn M.

    1995-05-01

    The long-term benefit of coronary or peripheral vascular interventions is limited by restenosis, due to intimal hyperplasia (IH). Photodynamic therapy (PDT) with systematic delivery of the photosensitizing drug, performed either at the time or shortly after vascular injury, has been demonstrated to effectively inhibit the development of experimental IH. However, in order to deliver large quantities of the photosensitizer, but avoid systematic photosensitization, local delivery of the drug appears to be an advantageous option. An experimental model was therefore developed to deliver benzporphyrin derivative (BPD-MA) directly into isolated segments of balloon-injured rat common carotid arteries, and to study the uptake in serum and arterial tissue by means of spectrofluorometry. Furthermore, early effects of local versus systematic drug delivery and subsequent PDT treatment, were investigated with light microscopy and morphometric analysis. Local delivery of BPD lead to effective drug concentrations in the artery with complete depletion of endothelial and smooth muscle cells, already 24 h after PDT. The media appeared compacted and acellular. No thrombosis or occlusion were observed. Serum concentrations of BPD, after local delivery, were at the detection threshold, whereas systematic application resulted in significantly higher serum but equivalent tissue drug concentrations. In conclusion, these data demonstrate that local delivery of BPD results in tissue concentrations, appropriate to perform an efficient vascular PDT treatment of the arterial wall.

  11. Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients.

    Science.gov (United States)

    Rudick, R A; Cutter, G R; Baier, M; Weinstock-Guttman, B; Mass, M K; Fisher, E; Miller, D M; Sandrock, A W

    2005-12-01

    Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNbeta-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of or = 6.0. Two methods were used to estimate the expected proportions that reached EDSS > or = 6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNbeta-1a patients reached an EDSS > or = 6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNbeta-1a patients should have reached an EDSS > or = 6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNbeta-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to

  12. Whether antithyroid drugs influence on the outcome of radioiodine therapy of thyroid functional autonomy?

    International Nuclear Information System (INIS)

    Full text: The purpose of research was an estimation of the influence of antithyroid medication on efficiency of radioiodine therapy (RIT) in patients with thyroid functional autonomy (FA). 100 patients with various clinical variants of FA were included in research and received treatment with radioiodine. From them uni-focal autonomy (UFA) was diagnosed in 65 person, multifocal (MFA) in 14 and disseminated (DA) in 21. Among the patients included in research 8 had relapse of hyperthyroidism after initial operative treatment and 1 after RIT. The data in work are submitted as a median (1-st and 3-rd quartiles). The age of surveyed was 65.5 (54; 72.5), from them 63 persons were a female, 37 were a male. From surveyed 2 groups of patients were formed. The first group consisted from 50 person, initially accepting during 4 months (2.5; 6) antithyroid drugs (ATD) which cancellation had been made as a rule 2 day prior to RIT, and the second one included 50 person, not accepting ATD neither up to nor after RIT. 9 elderly and multi morbid patients from the first group continued to accept ATD within several months after RIT. Carbimazole (n=45) or methimazole (n=5) in a dose of 10 mg (5; 10) were used as ATD. Therapeutic activity of 131I was calculated by means of Marinelli's formula. The target dose for UFA has made 400 Gy, for MFA and DA - 150 Gy. For calculation of thyroid uptake 24-hour radioiodine test was carried 2-3 day prior to RIT. Used activity of I-131 have made from 4.08 up to 58.89 mCi. Duration of inpatient stay has made 3 days (2; 5). In 4 months (4; 5) after RIT the successful result (euthyroidism or hypothyroidism) has been achieved in 48 (96 %) patients accepting ATD, and in 47 (94 %) patients who were not accepting last. Conclusion: The conclusion that antithyroid medication does not influence on the efficiency of RIT of FA was made. It was revealed that frequency of hypothyroidism after RIT in patients of the first group was higher (36 %) than in patients of

  13. A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy

    Science.gov (United States)

    Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

    2015-09-01

    Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. Electronic supplementary information (ESI) available

  14. Molecular fundamentals of drug interactions in the therapy of colorectal cancer

    OpenAIRE

    Katarzyna Regulska; Beata Stanisz; Miłosz Regulski; Paulina Gieremek

    2014-01-01

    Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical beha...

  15. Effectiveness of music therapy in state-trait anxiety rate of addicts in drug-free rehabilitation stage

    Directory of Open Access Journals (Sweden)

    E Soleimani

    2016-02-01

    Full Text Available Objective: This study was an attempt to investigate the effect of music therapy on addicts’ state-trait anxiety rate in the stage of drug-free rehabilitation. Method: A quasi-experimental research design, along with pretest-posttest and control group was employed for the conduct of this study. The statistical population of the study included the addicts in the rehabilitation stage who had referred to the clean collaborators rehabilitation camp in Ardebil province in November 2014. From this population, the number of 32 addicts in 16-50-year-old age range was selected as the participants of the study by convenience sampling method. State-Trait Anxiety Inventory was used for data collection. Results: The results of multivariate covariant analysis showed that there is a significant difference between control and experimental groups in state and trait anxiety. In other words, the state and trait anxiety of addicts in the experimental group had been reduced after music therapy. Conclusion: Considering the obtained results, it can be concluded that music therapy alone or along other psychological interventions can be an effective method for reducing addicts’ anxiety in drug-free rehabilitation stage.

  16. Enzyme-triggered nanomedicine: Drug release strategies in cancer therapy (Invited Review)

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Thompson, David H.; Kaasgaard, Thomas

    2010-01-01

    strategies include utilization of heat, light and ultrasound sensitive systems and in particular pH sensitive systems where the lower pH in endosomes induces drug release. Highly interesting are enzyme sensitive systems where overexpressed disease-associated enzymes are utilized to trigger drug release. The...... enzyme-based strategies are particularly interesting as they require no prior knowledge of the tumour localization. The basis of this review is an evaluation of the current status of drug delivery strategies focused on triggered drug release by disease-associated enzymes. We limit ourselves to reviewing...

  17. Continuing drug therapy while breastfeeding. Part 2. Common misconceptions of physicians.

    OpenAIRE

    Koren, G; Moretti, M.; Ito, S.

    1999-01-01

    QUESTION: Is there any way to predict whether a drug taken by a mother is safe for a suckling baby, or is it just trial and error? One of my patients is receiving lithium for manic depression. She wishes to breastfeed, but clinically there is no way she can discontinue the drug. My sources say the drug is incompatible with breastfeeding. ANSWER: The amount of drug available to a baby through breastmilk is estimated as the percentage of maternal dose per kg ingested by the baby. Because infant...

  18. Porphyrin-cyclodextrin conjugates as a nanosystem for versatile drug delivery and multimodal cancer therapy

    Czech Academy of Sciences Publication Activity Database

    Králová, Jarmila; Kejík, Z.; Bříza, T.; Poučková, P.; Kral, A.; Martásek, P.; Král, V.

    2010-01-01

    Roč. 53, č. 1 (2010), s. 128-138. ISSN 0022-2623 Institutional research plan: CEZ:AV0Z50520514 Keywords : photodynamic therapy * cancer therapy * porphyrin conjugate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.207, year: 2010

  19. Optimal Endpoint of Therapy in IBD: An Update on Factors Determining a Successful Drug Withdrawal

    Directory of Open Access Journals (Sweden)

    Anita Annaházi

    2015-01-01

    Full Text Available Ulcerative colitis (UC and Crohn’s disease (CD are chronic inflammatory disorders, which require long term treatment to achieve remission and to prevent relapses and cancer. While current therapies are effective in most cases, they can have rare but serious side effects and are often associated with high costs. On the other hand, early discontinuation of an effective treatment may lead to a quick relapse and to complications at the restart of therapy. Therefore it is essential to determine the optimal duration of maintenance therapy, but clear guidelines are missing. The most important questions when deciding whether to continue or withdraw therapy in quiescent UC and CD patients are the efficacy of the continuous treatment to maintain remission in the long term, the frequency and severity of side effects, and the chance of relapse after discontinuation of therapy. This review summarizes the current knowledge on these topics with respect to 5-aminosalicylates, thiopurines, methotrexate, and biological therapies and collects information regarding when and in which specific patient groups, in the absence of risk factors, can withdrawal of therapy be considered without a high risk of relapse. Additionally, the particular aspect of colorectal cancer prevention by current therapies will also be discussed.

  20. Development of novel polymeric materials for gene therapy and pH-sensitive drug delivery: Modeling, synthesis, characterization, and analysis

    Science.gov (United States)

    Anderson, Brian Curtis

    The aim of this work was to obtain a fundamental understanding of drug release mechanisms from polymers that undergo thermoreversible gelation and to synthesize new polymers based on these that exhibit both pH and temperature sensitivity. Novel block and random copolymers with cationic character have been developed for drug delivery and gene therapy applications. The development of these materials began with a study of the mechanism of drug release from poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block copolymers. This study revealed the release rates of drugs from water-soluble hydrogels composed of the PEO-PPO-PEO block copolymer PluronicRTM F127 was dictated almost solely by the rate of interfacial dissolution at the water/gel interface. A setup was designed to measure drug release from such soluble systems in order to avoid confounding hydrodynamic effects as a result of shear on the delicate polymer/gel interface. This study was followed by a complementary analysis of the effect ionic salts play in the phase transitions and drug release profiles in aqueous F127 solutions. In an attempt to incorporate pH sensitivity into such drug release systems, several block copolymers of poly(N,N-diethylaminoethyl methacrylate) (PDEAEM), PEO and PPO were synthesized via anionic polymerization. Diblock materials (PEO-b-PDEAEM), either with or without a carboxylic acid endcap, were synthesized and characterized. Tablet dissolution experiments demonstrated pH-sensitivity in their drug release profiles relative to PEO tablets. Pentablock materials (PDEAEM-b-PEO-b-PPO- b-PEO-b-PDEAEM) were synthesized that maintain the thermoreversible gelation and micellization properties of F127 while introducing pH-dependent release from aqueous gels of the copolymer. This is the first example of non-crosslinked materials that exhibit both pH- and temperature-sensitive behavior. Using a similar synthesis route, random copolymers of PDEAEM and poly(poly(ethylene glycol) methyl

  1. Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

    DEFF Research Database (Denmark)

    Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik;

    2014-01-01

    BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Af......BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub...... resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months). RESULTS: Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure...... was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI...

  2. Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension

    Directory of Open Access Journals (Sweden)

    Barkley Ruth

    2007-09-01

    Full Text Available Abstract Background As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA recruited 575 sibships (n = 1583 individuals from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs typed in 7 positional candidate genes, including adducin 2 (ADD2. Method To investigate whether blood pressure (BP levels in these hypertensives (n = 1133 were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup. These methods greatly reduced the chance of false positive findings. Results Eight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives (p-value Conclusion Our findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.

  3. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

    DEFF Research Database (Denmark)

    Wittkop, Linda; Günthard, Huldrych F; de Wolf, Frank;

    2011-01-01

    The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration....

  4. Changes in sexual and drug-related risk behavior following antiretroviral therapy initiation among HIV-infected injection drug users

    Science.gov (United States)

    Fu, Tsung-chieh; Westergaard, Ryan P.; Lau, Bryan; Celentano, David D.; Vlahov, David; Mehta, Shruti H.; Kirk, Gregory D.

    2013-01-01

    Objective To evaluate whether HAART is associated with subsequent sexual and drug-related risk behavior compensation among injection drug users (IDUs). Design A community-based cohort study of 362 HIV-infected IDUs initiating HAART in Baltimore, Maryland. Methods HAART use and risk behavior was assessed at 8316 biannual study visits (median 23). Using logistic regression with generalized estimating equations (GEE), we examined the effect of HAART initiation on changes in risk behavior while adjusting for sociodemographics, alcohol use, CD4+ cell count, year of initiation and consistency of HAART use. Results At HAART initiation, participants were a median of 44.4 years old, 71.3% men and 95.3% African–American. In multivariable analysis, HAART initiation was associated with a 75% reduction in the likelihood of unprotected sex [adjusted odds ratio (aOR) 0.25; 95% confidence interval (CI), 0.19–0.32] despite no change in overall sexual activity (aOR 0.95; 0.80–1.12). Odds of any injecting decreased by 38% (aOR 0.62; 0.51–0.75) after HAART initiation. Among the subset of persistent injectors, needle-sharing increased nearly two-fold (aOR 1.99; 1.57–2.52). Behavioral changes were sustained for more than 5 years after HAART initiation and did not differ by consistency of HAART use. Reporting specific high-risk behaviors in the year prior to initiation was a robust predictor of engaging in those behaviors subsequent to HAART. Conclusion Overall, substantial declines in sexual risk-taking and active injecting argue against significant behavioral compensation among IDUs following HAART initiation. These data also provide evidence to support identifying persons with risky pre-HAART behavior for targeted behavioral intervention. PMID:23079804

  5. Cell and gene therapy for arrhythmias: Repair of cardiac conduction damage

    Institute of Scientific and Technical Information of China (English)

    Yong-Fu Xiao

    2011-01-01

    Action potentials generated in the sinoatrial node(SAN)dominate the rhythm and rate of a healthy human heart.Subsequently,these action potentials propagate to the whole heart via its conduction system .Abnormalities of impulse generation and/or propagation in a heart can cause arrhythmias.For example,SAN dysfunction or conduction block of the atrioventricular node can lead to serious bradycardia which is currently treated with an implanted electronic pacemaker.On the other hand conduction damage may cause reentrant tachyarrhythmias which are primarily treated pharmacologically or by medical device-based therapies,including defibrillation and tissue ablation.However,drug therapies sometimes may not be effective or are associated with serious side effects.Device-based therapies for cardiac arrhythmias,even with well developed technology,still face inadequacies,limitations,hardware complications,and other challenges.Therefore,scientists are actively seeking other alternatives for antiarrhythmic therapy.In particular,cells and genes used for repairing cardiac conduction damage/defect have been investigated in various studies both in vitro and in vivo.Despite the complexities of the excitation and conduction systems of the heart,cell and gene-based strategies provide novel alternatives for treatment or cure of cardiac anhythmias.This review summarizes some highlights of recent research progress in this field.

  6. A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs

    Directory of Open Access Journals (Sweden)

    G. Pasero

    2011-09-01

    Full Text Available The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and infl ammation, but without any infl uence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs. This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and lefl unomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive (“therapeutic pyramid” or of more aggressive treatment, through the simultaneous use of two or more DMARDs (“combination therapy”.

  7. Noncompliance with drug therapy of glaucoma: a review about intervening factors

    Directory of Open Access Journals (Sweden)

    Aldemar Nemésio Brandão Vilela de Castro

    2009-09-01

    Full Text Available Glaucoma is defined as an optic neuropathy, characterized for loss of visual field and injury of the optic nerve, being considered as the second cause of blindness in the world, which could be prevented by the use of antiglaucoma eyedrops. The lack of adhesion of the patient to the drug treatment can culminate with loss of the vision. The objective was to revise possible literature data regarding intervening factors for noncompliance and explain estimated rates of noncompliance. A systematic review about the subject was carried out in the period of January to June of 2006. Articles had been searched in two data bases, in the National Library of Medicine (PUBMED and in the Literature Latin American and Caribbean Health Sciences (LILACS using the following keywords: glaucoma, compliance of the patient, noncompliance of the patient, treatment and eyedrops. In PUBMED, 199 articles were collected, written in English and French languages. No article was found in LILACS. Considering the inclusion and exclusion criteria, 27 articles were selected, with 25 originals and two reviews. Twelve possible intervening factors for noncompliance were raised, as well as estimates for rates of noncompliance. The noncompliance rates varied from 4.6% up to 59%. Two factors, forgetfulness and inadequate between-doses interval, had been associated to noncompliance of the drug therapy. The factors race, adverse effects, treatment cost, number of instilled doses, coexisting illnesses and number of eyedrops used, had resulted contradictory, being impossible to affirm that they have contributed for noncompliance. Age, sex, educational level and loss of visual field, had not been associated with noncompliance. The glaucoma patients tended to disregard the drug treatment. The wide variation in noncompliance rates could be an influence from the authors' difficulty to define the noncompliance and the variety of methodologies used to estimate it. More studies are necessary for a

  8. Compliance with new drugs in glaucoma therapy in Benin-city, Nigeria / Cumplimiento con los nuevos medicamentos antiglaucoma en Benin City - (Nigeria)

    OpenAIRE

    Omoti AE; Ukponmwan CU

    2005-01-01

    Objective: To determine the compliance rate, reasons for default and factors affecting compliance with new drugs in glaucoma therapy. Method: Fifty-six new patients on medical therapy with the recent drugs for primary open-angle glaucoma were followed-up for a minimum duration of 3 months and a maximum of 9 months. The number of drug doses missed per week as well as the reasons for default were recorded. Compliant and non-compliant patients were also compared in terms of prescribed treatment...

  9. Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings

    DEFF Research Database (Denmark)

    Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo;

    2014-01-01

    BACKGROUND: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations...... outcomes were assessed over 2015-2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used. RESULTS: The most effective strategy, in terms...... of the decision whether to switch to second line therapy was not cost-effective, even though the test was assumed to be very inexpensive....

  10. [Cardiogenic shock after drug therapy for atrial fibrillation with tachycardia : Case report of an 89-year-old woman].

    Science.gov (United States)

    Fey, H; Jost, M; Geise, A T; Bertsch, T; Christ, M

    2016-06-01

    β-Blockers and calcium channel blockers are commonly used drugs in the treatment of atrial fibrillation with tachycardia. However, in patients with high myocardial susceptibility and vulnerability, combination therapy with β-blockers and non-dihydropyridine calcium channel blockers (verapamil or diltiazem) but also individual administration can cause drug-induced cardiogenic shock. Thus, the simultaneous administration of β-blockers and non-dihydropyridine calcium channel blockers is absolutely contraindicated. In case of acute heart failure, isolated application is also contraindicated. In the treatment of a cardiogenic shock induced by β-blockers and/or non-dihydropyridine calcium channel blockers, administration of intravenous calcium, glucagon or high-dose insulin is recommended. PMID:26440099

  11. The role of multifunctional drug therapy as an antidote to combat experimental subacute neurotoxicity induced by organophosphate pesticides.

    Science.gov (United States)

    Singh, Satinderpal; Prakash, Atish; Kaur, Shamsherjit; Ming, Long Chiau; Mani, Vasudevan; Majeed, Abu Bakar Abdul

    2016-08-01

    Organophosphate pesticides are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants are potent inhibitors of cholinesterases leading to a massive build-up of acetylcholine which induces an array of deleterious effects, including convulsions, oxidative damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime yield a remarkable survival rate, but fail to prevent neuronal damage and behavioral problems. It has been indicated that multifunction drug therapy with potassium channel openers, calcium channel antagonists and antioxidants (either single-agent therapy or combination therapy) may have the potential to prevent cell death and/or slow down the processes of secondary neuronal damage. The aim of the present study, therefore, was to make a relative assessment of the potential effects of nicorandil (2 mg/kg), clinidipine (10 mg/kg), and grape seed proanthocyanidin (GSPE) extract (200 mg/kg) individually against subacute chlorpyrifos induced toxicity. The test drugs were administered to Wistar rats 2 h after exposure to Chlorpyrifos (CPF). Different behavioral studies and biochemical estimation has been carried in the study. The results showed that chronic administration of CPF significantly impaired learning and memory, along with motor coordination, and produced a marked increase in oxidative stress along with significantly reduced acetylcholine esterase (AChE) activity. Treatment with nicorandil, clinidipine and GSPE was shown to significantly improve memory performance, attenuate oxidative damage and enhance AChE activity in rats. The present study also suggests that a combination of nicorandil, clinidipine, and GSPE has a better neuroprotective effect against subacute CPF induced neurotoxicity than if applied individually. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1017-1026, 2016. PMID:25864908

  12. Identification of Down's syndrome critical locus gene SIM2-s as a drug therapy target for solid tumors

    OpenAIRE

    DeYoung, Maurice Phil; Tress, Matthew; Narayanan, Ramaswamy

    2003-01-01

    We report here a cancer drug therapy use of a gene involved in Down's syndrome. Using bioinformatics approaches, we recently predicted Single Minded 2 gene (SIM2) from Down's syndrome critical region to be specific to certain solid tumors. Involvement of SIM2 in solid tumors has not previously been reported. Intrigued by a possible association between a Down's syndrome gene and solid tumors, we monitored SIM2 expression in solid tumors. Isoform-specific expression of SIM2 short-form (SIM2-s) ...

  13. Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

    CERN Document Server

    Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

    2014-01-01

    Objectives: 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. Study design: 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). Methods: 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 swi...

  14. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

    2015-01-15

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  15. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    International Nuclear Information System (INIS)

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose

  16. Enzyme- and pH-Sensitive Branched Polymer-Doxorubicin Conjugate-Based Nanoscale Drug Delivery System for Cancer Therapy.

    Science.gov (United States)

    Wei, Xiaoli; Luo, Qiang; Sun, Ling; Li, Xue; Zhu, Hongyan; Guan, Pujun; Wu, Min; Luo, Kui; Gong, Qiyong

    2016-05-11

    Owing to their dendritic architectural features, branched copolymers have been investigated as drug delivery systems. In this paper, an enzyme- and pH-sensitive branched poly[N-(2-hydroxypropyl)methacrylamide] (polyHPMA) copolymer-doxorubicin (DOX) conjugate possessing a molecular weight (MW) of 165 kDa was designed and prepared via a one-pot reaction and drug conjugation. This conjugate's potential as a smart, nanoscale drug delivery system (NDDS) is also investigated. The branched conjugate was capable of forming nanoparticles with a negative surface charge. The self-assembled nanoparticles were 102 nm in diameter as measured by dynamic light scattering (DLS) and 95 nm in diameter via scanning electron microscopy, respectively. The nanoparticles were degraded to low-MW products (23∼25 kDa) in the presence of papain or cathepsin B, and the degradation was monitored via DLS and size-exclusion chromatography. The nanoparticles demonstrated pH-sensitive drug release, as the DOX was attached to the branched copolymer via a hydrazone bond. In comparison to free DOX, the conjugate-based nanoparticles exhibited greater accumulation in breast tumors, resulting in enhanced antitumor therapeutic indexes. Furthermore, widespread dissemination of the conjugate among breast tumor cells was confirmed by immunohistochemical assay. Finally, no obvious systemic toxicities were observed in vivo in normal mice. Thus, the branched HPMA copolymer-DOX conjugate may be employed as a safe and efficient pH- and enzyme-responsive NDDS for cancer therapy. PMID:27102364

  17. Development of Novel Polymeric Materials for Gene Therapy and pH-Sensitive Drug Delivery: Modeling, Synthesis, Characterization, and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brian Curtis Anderson

    2002-08-27

    The underlying theme of this thesis is the use of polymeric materials in bioapplications. Chapters 2-5 either develop a fundamental understanding of current materials used for bioapplications or establish protocols and procedures used in characterizing and synthesizing novel materials. In chapters 6 and 7 these principles and procedures are applied to the development of materials to be used for gene therapy and drug delivery. Chapter one is an introduction to the ideas that will be necessary to understand the subsequent chapters, as well as a literature review of these topics. Chapter two is a paper that has been published in the ''Journal of Controlled Release'' that examines the mechanism of drug release from a polymer gel, as well as experimental design suggestions for the evaluation of water soluble drug delivery systems. Chapter three is a paper that has been published in the ''Journal of Pharmaceutical Sciences'' that discusses the effect ionic salts have on properties of the polymer systems examined in chapter two. Chapter four is a paper published in the Materials Research Society Fall 2000 Symposium Series dealing with the design and synthesis of a pH-sensitive polymeric drug delivery device. Chapter five is a paper that has been published in the journal ''Biomaterials'' proposing a novel polymer/metal composite for use as a biomaterial in hip arthroplasty surgery. Chapter six is a paper that will appear in an upcoming volume of the Journal ''Biomaterials'' dealing with the synthesis of a novel water soluble cationic polymer with possible applications in non-viral gene therapy. Chapter seven is a paper that has been submitted to ''Macromolecules'' discussing several novel block copolymers based on poly(ethylene glycol) and poly(diethylamino ethyl methacrylate) that possess both pH-sensitive and temperature sensitive properties. Chapter eight contains a

  18. Comparison of the effects of DC031050,a class Ⅲ antiarrhythmic agent, on hERG channel and three neuronal potassium channels

    Institute of Scientific and Technical Information of China (English)

    Ping LI; Hai-feng SUN; Ping-zheng ZHOU; Chao-ying MA; Guo-yuan HU; Hua-liang JIANG; Min LI; Hong LIU; Zhao-bing GAO

    2012-01-01

    Aim:This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels.Methods:Human ether-à-go-go related gene (hERG),KCNQ and Kv1.2 channels were expressed in CHO cells.The delayed rectifier potassium current (IK) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats.Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents.Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer.Results:Both DC031050 and dofetilide potently inhibited hERG currents with IC50 values of 2.3±1.0 and 17.9±1.2 nmol/L,respectively.DC031050 inhibited the IK current with an IC50 value of 2.7±1.5 μmol/L,which was >1000 times the concentration required to inhibit hERG current.DC031050 at 3 μmol/L did not significantly affect the voltage-dependence of the steady activation,steady inactivation of IK,or the rate of IK from inactivation.Intracellular application of DC031050 (5μmol/L) was insufficient to inhibit IK.DC031050 up to 10μmol/L had no effects on KCNQ2 and Kv1.2 channel currents.Conclusion:DC031050 is a highly selective hERG potassium channel blocker with a substantial safety margin of activity over neuronal potassium channels,thus holds significant potential for therapeutic application as a class Ⅲ antiarrhythmic agent.

  19. High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba

    Science.gov (United States)

    Kouri, Vivian; Alemán, Yoan; Pérez, Lissette; Pérez, Jorge; Fonseca, Carlos; Correa, Consuelo; Aragonés, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Vinken, Lore; Limia, Celia; Soto, Yudira; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2014-01-01

    Introduction Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba. Methods This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009–2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2. Results Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years) and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients from 2011–2013. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009–2010 and 2011–2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002). Conclusions Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure. PMID:25397499

  20. High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba

    Directory of Open Access Journals (Sweden)

    Vivian Kouri

    2014-11-01

    Full Text Available Introduction: Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba. Methods: This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009–2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2. Results: Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years and exposed to more ART regimens (median: 4 vs 2 regimens compared to patients from 2011–2013. Nucleoside reverse transcriptase inhibitor (NRTI, non-nucleoside RTI (NNRTI and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR to NRTI, NNRTI, PI and multidrug resistance (MDR were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients. Subtype B (32.5%, BG recombinants (19.6% and CRF19_cpx (16.2% were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009–2010 and 2011–2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002. Conclusions: Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure.

  1. Torsade de pointes tachycardia in a patient on dronedarone therapy.

    Science.gov (United States)

    Huemer, Martin; Sarganas, Giselle; Bronder, Elisabeth; Klimpel, Andreas; Garbe, Edeltraut; Haverkamp, Wilhelm

    2015-05-01

    Dronedarone is a promising, relatively new antiarrhythmic agent characterized by structural similarities to amiodarone but without amiodarone's severe organ toxicity. The proarrhythmic potential of dronedarone, however, is of increasing concern. We describe a 76-year-old woman who had been receiving dronedarone 400 mg twice/day to prevent recurrent atrial tachycardia with rapid ventricular response. Several months later, she came to the emergency department with decompensated congestive heart failure and episodes of atrial tachycardia; digoxin 0.5 mg and furosemide 40 mg were administered intravenously. Thereafter nonsustained torsade de pointes (TdP) tachycardia occurred. She was transferred to the intensive care unit where a dose of amiodarone 150 mg was administered intravenously by mistake. Thereafter, the patient showed sustained TdP necessitating cardiac resuscitation. Dronedarone was discontinued, and digoxin and amiodarone were not administered again. Under dronedarone a relevant QT prolongation was documented that was additionally augmented after concomitant treatment with digoxin and amiodarone. Use of the Naranjo adverse drug reaction probability scale indicated a probable adverse drug reaction to dronedarone (score of 7). To our knowledge, this is the first case report of a patient who experienced TdP tachycardias while receiving dronedarone therapy in connection with a worsening of heart failure and possible drug interactions with digoxin and amiodarone. Clinicians should be aware of this potential adverse drug reaction and perform repeated heart rate-corrected QT (QTc) interval measurements as well as screening for congestive heart failure in patients receiving dronedarone therapy. PMID:25823967

  2. Compliance with new drugs in glaucoma therapy in Benin-city, Nigeria / Cumplimiento con los nuevos medicamentos antiglaucoma en Benin City - (Nigeria

    Directory of Open Access Journals (Sweden)

    Omoti AE

    2005-10-01

    Full Text Available Objective: To determine the compliance rate, reasons for default and factors affecting compliance with new drugs in glaucoma therapy. Method: Fifty-six new patients on medical therapy with the recent drugs for primary open-angle glaucoma were followed-up for a minimum duration of 3 months and a maximum of 9 months. The number of drug doses missed per week as well as the reasons for default were recorded. Compliant and non-compliant patients were also compared in terms of prescribed treatment and personal characteristics. Results: The most commonly prescribed drugs were topical dorzolamide, brinzolamide, latanoprost, apraclonidine and travoprost. The non-compliance rate was 66.1%. Major reasons for defaulting were side effects (36.6%, scarcity of drugs (22% and high cost of drugs (12.2%. Knowledge of glaucoma was significantly associated with good compliance (p<0.01. Conclusion: The level of compliance with new drugs in glaucoma therapy is very poor. Health education and the provision of affordable, accessible and appropriate medical therapy are required.

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

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Kamper, Anne-Lise; Køber, Lars;

    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...

  4. Cryptococcal therapies and drug targets: the old, the new and the promising.

    Science.gov (United States)

    Coelho, Carolina; Casadevall, Arturo

    2016-06-01

    Half a century after the introduction of Amphotericin B the management of cryptococcosis remains unsatisfactory. The disease, caused primarily by the two fungal species Cryptococcus neoformans and Cryptococcus gattii, remains responsible for considerable morbidity and mortality despite standard medical care. Current therapeutic options are limited to Amphotericin B, azoles and 5-flucytosine. However, this organism has numerous well-characterized virulence mechanisms that are amenable to pharmacological interference and are thus potential therapeutic targets. Here, we discuss existing approved antifungal drugs, resistance mechanisms to these drugs and non-standard antifungal drugs that have potential in treatment of cryptococcosis, including immunomodulatory strategies that synergize with antifungal drugs, such as cytokine administration or monoclonal antibodies. Finally, we summarize attempts to target well-described virulence factors of Cryptococcus, the capsule or fungal melanin. This review emphasizes the pressing need for new therapeutic alternatives for cryptococcosis. PMID:26990050

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

    OpenAIRE

    Roberta Balansin Rigon; Márcia Helena Oyafuso; Andressa Terumi Fujimura; Maíra Lima Gonçalez; Alice Haddad do Prado; Maria Palmira Daflon Gremião; Marlus Chorilli

    2015-01-01

    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 adv...

  6. Monitoring early tumor response to drug therapy with diffuse optical tomography

    OpenAIRE

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L; Johung, Tessa B.; Gander, Jeffrey W; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy—thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture phy...

  7. Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored Therapies?

    OpenAIRE

    Carla Pollastro; Carmela Ziviello; Valerio Costa; Alfredo Ciccodicola

    2015-01-01

    Type 2 diabetes is one of the major causes of mortality with rapidly increasing prevalence. Pharmacological treatment is the first recommended approach after failure in lifestyle changes. However, a significant number of patients shows—or develops along time and disease progression—drug resistance. In addition, not all type 2 diabetic patients have the same responsiveness to drug treatment. Despite the presence of nongenetic factors (hepatic, renal, and intestinal), most of such variability i...

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

    OpenAIRE

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

    2015-01-01

    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 ...

  9. Dependent Prior: An Application in Spinal Anaesthesia Drug Therapy on SBP in Cesarean patients.

    Directory of Open Access Journals (Sweden)

    Atanu Bhattacharjee

    2013-12-01

    Full Text Available Cesarean section is widely used operation procedure in the world. The regional anesthesia is preferred than general anesthesia. The risk of fetus is higher in general than in regional anesthesia. The drug treatment effect on regional anesthesia plays an important role to control the systolic blood pressure (SBP during the surgery. The goal of this work is to know the effective drug to control the SBP among cesarean anesthetic patients. The dependent prior with Bayesian approach is applied in the binary response data set. The secondary data in anesthesia has been applied to compare the two drug treatments, viz. (1 Phenylephrine and (2 Ephedrine, in cesarean patients with spinal anesthesia. In both drug groups the mean of SBP has been found controlled over the duration of the surgery. No rapid changes of SBP level among the patients are observed. At the end of study it is found that the means of SBP cesarean anesthetic patients are found higher in Phenylephrine group. The Bayesian dependent prior is found to offer effective tool for drug treatment effect comparison. The drug treatment effect Ephedrine is found to be more effective to control the SBP over the duration of surgery than Phenylephrine.

  10. The influence of relative humidity on the cohesion properties of micronized drugs used in inhalation therapy.

    Science.gov (United States)

    Young, Paul M; Price, Robert; Tobyn, Michael J; Buttrum, Mark; Dey, Fiona

    2004-03-01

    The influence of relative humidity (RH) on the cohesion properties of three drugs: salbutamol sulphate (SS), triamcinolone acetonide (TAA), and disodium cromoglycate (DSCG) was investigated using the atomic force microscope (AFM) colloidal probe technique. Micronized drug particles were mounted in heat-sensitive epoxy resin for immobilization. Multiple AFM force-distance curves were conducted between each drug probe and the immobilized drug particulates at 15, 45, and 75% RH using Force-Volume imaging. Clear variations in the cohesion profile with respect to RH were observed for all three micronized drugs. The calculated force and energy of cohesion to separate either micronized SS or DSCG increased as humidity was raised from 15 to 75% RH, suggesting capillary forces become a dominating factor at elevated RH. In comparison, the separation force and energy for micronized TAA particles decreased with increased RH. This behavior may be attributed to long-range attractive electrostatic interactions, which were observed in the approach cycle of the AFM force-distance curves. These observations correlated well with previous aerosolization studies of the three micronized drugs. PMID:14762913

  11. Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya

    Directory of Open Access Journals (Sweden)

    Reynaerts Jacqueline

    2009-06-01

    Full Text Available Abstract Access to antiretroviral therapy (ART is increasing in resource-limited settings (RLS and can successfully reduce HIV-related morbidity and mortality. However, virologic failure and development of viral drug resistance can result in reduced treatment options and disease progression. Additionally, transmission of resistant virus, and particularly multi-drug resistance, could become a public health concern. This study evaluated treatment success and development of ART drug resistance after short-term treatment among patients attending the Comprehensive HIV Care Centre (CCC of Coast Province General Hospital, Mombasa, Kenya. One hundred and fifty HIV-infected individuals receiving ART were consecutively recruited to participate in the study. After determination of plasma viral load, patients with detectable viral load levels were subjected to genotypic drug resistance testing. At the time of sampling, 132 of the 150 participants were on ART for more than 6 months (median 21 months, IQR = 12–26. An efficient viral load reduction to below 50 copies/ml was observed in 113 (85.6% of them. Of the 19 patients with a detectable viral load, sequencing of the protease (PR and reverse transcriptase (RT gene was successful in 16. Eleven (11 of these 16 patients were infected with a subtype A1 virus. Major PR mutations were absent, but mutations associated with drug resistance in RT were detected in 14 of the 16 patients (87.5%. High-level resistance against at least 2 drugs of the ART regimen was observed in 9/14 (64.3%. The 3TC mutation M184V and the NNRTI mutation K103N were most frequent but also the multi-drug resistance Q151M and the broad NRTI cross-resistance K65R were observed. The results of this study revealed a high rate of treatment success after short term ART in patients treated at a public provincial hospital in a RLS. Nevertheless, the observed high risk of accumulation of resistance mutations among patients failing treatment and

  12. How treatment affects the brain: meta-analysis evidence of neural substrates underpinning drug therapy and psychotherapy in major depression.

    Science.gov (United States)

    Boccia, Maddalena; Piccardi, Laura; Guariglia, Paola

    2016-06-01

    The idea that modifications of affect, behavior and cognition produced by psychotherapy are mediated by biological underpinnings predates the advent of the modern neurosciences. Recently, several studies demonstrated that psychotherapy outcomes are linked to modifications in specific brain regions. This opened the debate over the similarities and dissimilarities between psychotherapy and pharmacotherapy. In this study, we used activation likelihood estimation meta-analysis to investigate the effects of psychotherapy (PsyTh) and pharmacotherapy (DrugTh) on brain functioning in Major Depression (MD). Our results demonstrate that the two therapies modify different neural circuits. Specifically, PsyTh induces selective modifications in the left inferior and superior frontal gyri, middle temporal gyrus, lingual gyrus and middle cingulate cortex, as well as in the right middle frontal gyrus and precentral gyrus. Otherwise, DrugTh selectively affected brain activation in the right insula in MD patients. These results are in line with previous evidence of the synergy between psychotherapy and pharmacotherapy but they also demonstrate that the two therapies have different neural underpinnings. PMID:26164169

  13. Activated Charge-Reversal Polymeric Nano-System: The Promising Strategy in Drug Delivery for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yichen Hu

    2016-04-01

    Full Text Available Various polymeric nanoparticles (NPs with optimal size, tumor-targeting functionalization, or microenvironment sensitive characteristics have been designed to solve several limitations of conventional chemotherapy. Nano-sized polymeric drug carrier systems have remarkably great advantages in drug delivery and cancer therapy, which are still plagued with severe deficiencies, especially insufficient cellular uptake. Recently, surface charge of medical NPs has been demonstrated to play an important role in cellular uptake. NPs with positive charge show higher affinity to anionic cell membranes such that with more efficient cellular internalization, but otherwise cause severe aggregation and fast clearance in circulation. Thus, surface charge-reversal NPs, specifically activated at the tumor site, have shown to elegantly resolve the enhanced cellular uptake in cancer cells vs. non-specific protein adsorption dilemma. Herein, this review mainly focuses on the effect of tumor-site activated surface charge reversal NPs on tumor treatment, including the activated mechanisms and various applications in suppressing cancer cells, killing cancer stem cell and overcoming multidrug resistance, with the emphasis on recent research in these fields. With the comprehensive and in-depth understanding of the activated surface charge reversal NPs, this approach might arouse great interest of scientific research on enhanced efficient polymeric nano-carriers in cancer therapy.

  14. Visualization of diffusion of the drug solution during aluminum potassium tannic acid injection therapy: a pilot study.

    Science.gov (United States)

    Yamamoto, Yutaka; Miwa, Mitsuharu

    2013-06-01

    Sclerotherapy with aluminum potassium tannic acid (ALTA), which was approved in Japan for the treatment of internal hemorrhoids in July 2004 (Takano et al., Int J Colorectal Dis 21:44-51, 2006), has been widely accepted because of its effectiveness and low invasiveness. More than 200,000 patients have received ALTA injection therapy. ALTA is injected directly into 4 points of an internal hemorrhoid (4-step injection) to induce sclerosis and remission of the hemorrhoids, and consequently, resolution of symptoms such as prolapse and bleeding. The precision of the 4-step injection is considered to be a crucial determinant of the success of this therapy and the risk of complications. However, sufficient evidence has not yet been obtained concerning the diffusion and distribution of the injected drug. A pilot study visualized the real-time diffusion/distribution of the drug solution following the 4-step injection, using the ICG (indocyanine green) fluorescence technique, and an infrared camera (Photodynamic EYE; PDE, Hamamatsu Photonics K.K.). PMID:23229838

  15. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Toledo JO

    2015-01-01

    Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

  16. Role of cytochrome P450 genotype in the steps toward personalized drug therapy

    Directory of Open Access Journals (Sweden)

    Cavallari LH

    2011-11-01

    Full Text Available Larisa H Cavallari1,2, Hyunyoung Jeong1,2, Adam Bress11Department of Pharmacy Practice, 2Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USAAbstract: Genetic polymorphism for cytochrome 450 (P450 enzymes leads to interindividual variability in the plasma concentrations of many drugs. In some cases, P450 genotype results in decreased enzyme activity and an increased risk for adverse drug effects. For example, individuals with the CYP2D6 loss-of-function genotype are at increased risk for ventricular arrhythmia if treated with usual does of thioridazine. In other cases, P450 genotype may influence the dose of a drug required to achieve a desired effect. This is the case with warfarin, with lower doses often necessary in carriers of a variant CYP2C9*2 or *3 allele to avoid supratherapeutic anticoagulation. When a prodrug, such as clopidogrel or codeine, must undergo hepatic biotransformation to its active form, a loss-of-function P450 genotype leads to reduced concentrations of the active drug and decreased drug efficacy. In contrast, patients with multiple CYP2D6 gene copies are at risk for opioid-related toxicity if treated with usual doses of codeine-containing analgesics. At least 25 drugs contain information in their US Food and Drug Administration-approved labeling regarding P450 genotype. The CYP2C9, CYP2C19, and CYP2D6 genes are the P450 genes most often cited. To date, integration of P450 genetic information into clinical decision making is limited. However, some institutions are beginning to embrace routine P450 genotyping to assist in the treatment of their patients. Genotyping for P450 variants may carry less risk for discrimination compared with genotyping for disease-associated variants. As such, P450 genotyping is likely to lead the way in the clinical implementation of pharmacogenomics. This review discusses variability in the CYP2C9, CYP2C19, and CYP2D6 genes and the

  17. In vitro and in vivo evaluation of drug-eluting microspheres designed for transarterial chemoembolization therapy.

    Science.gov (United States)

    Wang, Yujing; Molin, Daniël G M; Sevrin, Chantal; Grandfils, Christian; van den Akker, Nynke M S; Gagliardi, Mick; Knetsch, Menno L; Delhaas, Tammo; Koole, Leo H

    2016-04-30

    Poly(d,l-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafenib tosylate, were prepared, characterized and studied. Degradation of the microspheres, and release of cisplatin and/or sorafenib tosylate from them, were investigated in detail. Incubation of the drug-carrying microspheres in phosphate buffered saline (pH=7.4) revealed slow degradation. Nevertheless, significant release of cisplatin and sorafenib tosylate from microspheres loaded with both drugs was apparent in vitro; this can be attributed to their porous structure. Supernatants from microspheres loaded with both drugs showed strong toxic effects on cells (i.e. endothelial cells, fibroblast cells and Renca tumor cells) and potent anti-angiogenic effect in the matrigel endothelial tube assay. In vivo anti-tumor effects of the microspheres were also observed, in a Renca tumor mouse model. The poly(d,l-lactic acid) microspheres containing both cisplatin and sorafenib tosylate revealed highest therapeutic efficacy, probably demonstrating that combined local administration of cisplatin and sorafenib tosylate synergistically inhibits tumor growth in situ. In conclusion, this study demonstrates the applicability of biodegradable poly(d,l-lactic acid) microspheres loaded with cisplatin and sorafenib tosylate for local drug delivery as well as the potential of these microspheres for future use in transarterial chemoembolization. PMID:26965198

  18. Vitamin B12-loaded solid lipid nanoparticles as a drug carrier in cancer therapy.

    Science.gov (United States)

    Genç, Lütfi; Kutlu, H Mehtap; Güney, Gamze

    2015-05-01

    Nanostructure-mediated drug delivery, a key technology for the realization of nanomedicine, has the potential to improve drug bioavailability, ameliorate release deviation of drug molecules and enable precision drug targeting. Due to their multifunctional properties, solid lipid nanoparticles (SLNs) have received great attention of scientists to find a solution to cancer. Vitamin supplements may contribute to a reduction in the risk of cancer. Vitamin B12 has several characteristics that make it an attractive entity for cancer treatment and possible therapeutic applications. The aim of this study was to produce B12-loaded SLNs (B12-SLNs) and determine the cytotoxic effects of B12-SLNs on H-Ras 5RP7 and NIH/3T3 control cell line. Results obtained by MTT assay, transmission electron and confocal microscopy showed that B12-loaded SLNs are more effective than free vitamin B12 on cancer cells. In addition, characterization studies indicate that while the average diameter of the B12 was about 650 nm, B12-SLNs were about 200 nm and the drug release efficiency of vit. B12 by means of SLNs increased up to 3 h. These observations point to the fact that B12-SLNs could be used as carrier systems due to the therapeutic effects on cancer. PMID:24344935

  19. Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis

    International Nuclear Information System (INIS)

    In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves' disease. (author)

  20. Combined therapy of irradiation and drug treatment in primary brain tumours

    International Nuclear Information System (INIS)

    Combinations of radiation - drug regimes in malignant brain tumours are not generally established. The reasons for their limited clinical use are due to the selective permeability of the blood/brain barrier to cytostatic drugs and the increased risk of acute and late effects by altered pathophysiology. Therefore, the effects of combined modality of radio- and chemotherapy in malignant neoplasms of the central nervous system such as malignant gliomas and medulloblastomas should be studied only in randomized trials. In spite of promising experimental results effective radiosensitizing agents are not available for clinical use. The biological response modifiers (Interferons, TNF, IL-2) are now introduced for clinical evaluations, but preliminary results postpone the hope for improvement the therapeutical results to following drug generations. (orig.)

  1. Theranostic applications of nanomaterials in cancer: Drug delivery, image-guided therapy and multifunctional platforms

    OpenAIRE

    Fernandez-Fernandez, Alicia; Manchanda, Romila; Mcgoron, Anthony J.

    2011-01-01

    Successful cancer management depends on accurate diagnostics along with specific treatment protocols. Current diagnostic techniques need to be improved to provide earlier detection capabilities, and traditional chemotherapy approaches to cancer treatment are limited by lack of specificity and systemic toxicity. This review highlights advances in nanotechnology that have allowed the development of multifunctional platforms for cancer detection, therapy, and monitoring. Nanomaterials can be use...

  2. Therapist Adherence in Brief Strategic Family Therapy for Adolescent Drug Abusers

    Science.gov (United States)

    Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Puccinelli, Marc J.; Henderson, Craig; Szapocznik, Jose

    2011-01-01

    Objective: Therapist adherence has been shown to predict clinical outcomes in family therapy. In prior studies, adherence has been represented broadly by core principles and a consistent family (vs. individual) focus. To date, these studies have not captured the range of clinical skills that are represented in complex family-based approaches or…

  3. Effect of drug therapy on HEDIS measurements of HbA1c control in diabetes patients.

    Science.gov (United States)

    Bazalo, Gary; Weiss, Richard; Clark, Nathaniel; Alemayehu, Berhanu; Forma, Felicia; Ingram, Garrett

    2009-02-01

    The purpose of this study was to corroborate an earlier study that explored the relationship between a health plan's Health Plan Employer Data and Information Set (HEDIS) score for glycolated hemoglobin (HbA1c) control in diabetes patients and its utilization of insulin and oral diabetes products. Prescription volumes were tracked for four categories of diabetes drug therapy: analog insulin, human insulin, single-source brand oral products, and multisource generic oral products, for calendar years 2005 and 2006. The prescription shares of each of the four drug categories for each health plan were matched to the health plan's HEDIS measurements of HbA1c control for each year. Univariate and multivariate regression analysis was performed between the health plan's HbA1c -based HEDIS score and its prescription share of each drug category. A favorable and statistically significant (p brand (statistically significant) and the multisource generic oral category prescription shares (not significant). These results corroborate the relationships found in our earlier study, although a cause and effect relationship cannot be confirmed. PMID:19264026

  4. Drug: D00358 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00358 Drug Lidocaine (JP16/USP/INN); Dentipatch (TN); Xylocaine (TN) C14H22N2O 234...cal anesthetics 1214 Xylidines D00358 Lidocaine (JP16/USP/INN) Anatomical Therapeutic Chemical (ATC) classif...MICS, CLASS I AND III C01BB Antiarrhythmics, class Ib C01BB01 Lidocaine D00358 Lidocaine (JP16/USP/INN) C05 ...VASOPROTECTIVES C05A AGENTS FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE C05AD Local anesthetics C05AD01 Lidocai...ne D00358 Lidocaine (JP16/USP/INN) D DERMATOLOGICALS D04 AN

  5. Drug: D07465 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07465 Drug Arotinolol (INN) C15H21N3O2S3 371.0796 371.5411 D07465.gif Antiarrhythmic alpha1-adr...energic receptor antagonist [HSA:146 147 148] [KO:K04137 K04136 K04135]; beta1-adrenergic recep...tor antagonist [HSA:153] [KO:K04141]; beta2-adrenergic receptor antagonist [HSA:154] [KO:K04142]; beta3-adre...61(146+147+148+153+154) Adrenergic signaling in cardiomyocytes hsa04270(146+147+148) Vascular smooth muscle ...contraction hsa04970(146+147+148+153+154+155) Salivary secretion map07214 beta-Adr

  6. Development of special medical foods and botanical drugs using HemoHIM for cancer patients during radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran

    2010-02-15

    In vivo evaluation on the reductive effects of HemoHIM on the side-effects of radiation and anticancer drug treatment. - Evaluation on the promoting effects of HemoHIM on the tumor growth inhibitory activities of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of the reductive effects of HemoHIM on the immune suppressive side-effects of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of reductive effects of HemoHIM on the self-renewal tissue(intestine) damage of radiation and anticancer drug(5-FU) in mice. {center_dot} Assessment of toxicological safety of HemoHIM (GLP) and establishment of analytical methods for active/index components of HemoHIM - Assurance of toxicological safety in single-dose and 3 month repeat-dose toxicity test in rats - Establishment of analytical methods for active/index compounds and content analysis result in various production lots. {center_dot} Production of Special Medical Food pilot products for cancer patients and development of dosage forms for the natural new drugs. - Establishment of optimal formulations including HemoHIM for the Special Medical Food - Production of Special Medical Food pilot products for clinical test, analysis of nutrients, and official declaration of food production - Establishment of production process of HemoHIM for natural drug and production of pilot products for toxicity tests - Development of drug dosage forms of HemoHIM (tablet, granule, capsule) {center_dot} Clinical evaluation of HemoHIM on reduction of side-effects of radiation and chemotherapy in cancer patients - Subjects: breast cancer patients who completed surgical operation and chemotherapy, HemoHIM administration during and after the radiation therapy (HemoHIM group: 15, placebo group 13) - Administration period: 3 months from few days before RT commencement - Results - Improvement of immunological biomarkers (immune cell subpopulations, cytokine production) - Reduction of and enhanced

  7. Development of special medical foods and botanical drugs using HemoHIM for cancer patients during radiation therapy

    International Nuclear Information System (INIS)

    In vivo evaluation on the reductive effects of HemoHIM on the side-effects of radiation and anticancer drug treatment. - Evaluation on the promoting effects of HemoHIM on the tumor growth inhibitory activities of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of the reductive effects of HemoHIM on the immune suppressive side-effects of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of reductive effects of HemoHIM on the self-renewal tissue(intestine) damage of radiation and anticancer drug(5-FU) in mice. · Assessment of toxicological safety of HemoHIM (GLP) and establishment of analytical methods for active/index components of HemoHIM - Assurance of toxicological safety in single-dose and 3 month repeat-dose toxicity test in rats - Establishment of analytical methods for active/index compounds and content analysis result in various production lots. · Production of Special Medical Food pilot products for cancer patients and development of dosage forms for the natural new drugs. - Establishment of optimal formulations including HemoHIM for the Special Medical Food - Production of Special Medical Food pilot products for clinical test, analysis of nutrients, and official declaration of food production - Establishment of production process of HemoHIM for natural drug and production of pilot products for toxicity tests - Development of drug dosage forms of HemoHIM (tablet, granule, capsule) · Clinical evaluation of HemoHIM on reduction of side-effects of radiation and chemotherapy in cancer patients - Subjects: breast cancer patients who completed surgical operation and chemotherapy, HemoHIM administration during and after the radiation therapy (HemoHIM group: 15, placebo group 13) - Administration period: 3 months from few days before RT commencement - Results - Improvement of immunological biomarkers (immune cell subpopulations, cytokine production) - Reduction of and enhanced recovery from radiation skin

  8. Hepatocyte growth factor gene therapy reduces ventricular arrhythmia in animal models of myocardial ischemia.

    Directory of Open Access Journals (Sweden)

    Yumoto,Akihisa

    2005-06-01

    Full Text Available

    It was recently reported that gene therapy using hepatocyte growth factor (HGF has the potential to preserve cardiac function after myocardial ischemia. We speculated that this HGF gene therapy could also prevent ventricular arrhythmia. To investigate this possibility, we examined the antiarrhythmic effect of HGF gene therapy in rat acute and old myocardial infarction models. Myocardial ischemia was induced by ligation of the left descending coronary artery. Hemagglutinating virus of Japan (HVJ-coated liposome containing HGF genes were injected directly into the myocardium fourteen days before programmed pacing. Ventricular fibrillation (VFwas induced by programmed pacing. The VF duration was reduced and the VF threshold increased after HGF gene therapy ( p< 0.01. Histological analyses revealed that the number of vessels in the ischemic border zone was greatly increased after HGF gene injection. These findings revealed that HGF gene therapy has an anti-arrhythmic effect after myocardial ischemia.

  9. Current status and future prospects of therapeutic drug monitoring and applied clinical pharmacology in antiretroviral therapy.

    NARCIS (Netherlands)

    Boffito, M.; Acosta, E.; Burger, D.M.; Fletcher, C.V.; Flexner, C.; Garaffo, R.; Gatti, G.; Kurowski, M.; Perno, C.F.; Peytavin, G.; Regazzi, M.; Back, D.

    2005-01-01

    The consensus of current international guidelines for the treatment of HIV infection is that data on therapeutic drug monitoring (TDM) of non-nucleoside reverse transcriptase inhibitors and protease inhibitors provide a framework for the implementation of TDM in certain defined scenarios in clinical

  10. Fulminant hepatic failure following marijuana drug abuse: Molecular adsorbent recirculation system therapy

    OpenAIRE

    Swarnalatha, G.; Pai, S.; Ram, R.; Dakshinamurty, K. V.

    2013-01-01

    Marijuana is used for psychoactive and recreational purpose. We report a case of fulminant hepatic failure following marijuana drug abuse who recovered following artificial support systems for acute liver failure. There is no published literature of management of marijuana intoxication with molecular adsorbent recirculation system (MARS). MARS is effective and safe in patients with fulminant hepatic failure following marijuana intoxication.

  11. Efficiency of drug therapy in complex rehabilitation of patients in late recovery period of stroke

    OpenAIRE

    Dilshod Sagatov

    2011-01-01

    Clinical and neurological studies in 73 patients (44 men and 29 women) with the consequences of ischemic stroke in late recovery period were performed. Dopplerographic and electroencephalographic parameters before and after the rehabilitation measures were examined. In this study, we assessed the therapeutic effect of nootropics in drug rehabilitation with the inclusion of Nootropil and Cavinton Forte in late stroke recovery period.

  12. Ventricular Tachycardia in the Young Athlete: A Systematic Approach to Selection of Drug Therapy.

    Science.gov (United States)

    Podrid, Philip J.

    1986-01-01

    Sustained ventricular tachyarrythmias are uncommon in young people, and underlying heart disease is usually present. This article presents a case study of a 24-year-old male athlete with arrhythmogenic right ventricular dysplasia and points out the value of combinations of drugs versus the use of a single agent. (MT)

  13. Effect of amiodarone, an antiarrhythmic drug, on serum and liver lipids and serum marker enzymes in rats.

    Science.gov (United States)

    Padmavathy, B; Devaraj, S N; Devaraj, H

    1992-12-01

    Administration of amiodarone (AD) to rats leads to marked damage to liver, as evidenced by pathological changes and significant increases in activities of serum marker enzymes and levels of lipids like cholesterol and phospholipids with no alteration in the triglyceride levels. The risk factor, that is the total cholesterol/HDL cholesterol ratio, exhibited increase in the experimental animals, indicating that amiodarone treatment may lead to the development of coronary heart disease. PMID:1294474

  14. Ischemia-related subcellular redistribution of sodium channels enhances the proarrhythmic effect of class I antiarrhythmic drugs: a simulation study.

    Directory of Open Access Journals (Sweden)

    Kunichika Tsumoto

    Full Text Available Cardiomyocytes located at the ischemic border zone of infarcted ventricle are accompanied by redistribution of gap junctions, which mediate electrical transmission between cardiomyocytes. This ischemic border zone provides an arrhythmogenic substrate. It was also shown that sodium (Na+ channels are redistributed within myocytes located in the ischemic border zone. However, the roles of the subcellular redistribution of Na+ channels in the arrhythmogenicity under ischemia remain unclear.Computer simulations of excitation conduction were performed in a myofiber model incorporating both subcellular Na+ channel redistribution and the electric field mechanism, taking into account the intercellular cleft potentials.We found in the myofiber model that the subcellular redistribution of the Na+ channels under myocardial ischemia, decreasing in Na+ channel expression of the lateral cell membrane of each myocyte, decreased the tissue excitability, resulting in conduction slowing even without any ischemia-related electrophysiological change. The conventional model (i.e., without the electric field mechanism did not reproduce the conduction slowing caused by the subcellular Na+ channel redistribution. Furthermore, Na+ channel blockade with the coexistence of a non-ischemic zone with an ischemic border zone expanded the vulnerable period for reentrant tachyarrhythmias compared to the model without the ischemic border zone. Na+ channel blockade tended to cause unidirectional conduction block at sites near the ischemic border zone. Thus, such a unidirectional conduction block induced by a premature stimulus at sites near the ischemic border zone is associated with the initiation of reentrant tachyarrhythmias.Proarrhythmia of Na+ channel blockade in patients with old myocardial infarction might be partly attributable to the ischemia-related subcellular Na+ channel redistribution.

  15. TRPV1 channel as a target for cancer therapy using CNT-based drug delivery systems.

    Science.gov (United States)

    Ortega-Guerrero, Andres; Espinosa-Duran, John M; Velasco-Medina, Jaime

    2016-07-01

    Carbon nanotubes are being considered for the design of drug delivery systems (DDSs) due to their capacity to internalize molecules and control their release. However, for cellular uptake of drugs, this approach requires an active translocation pathway or a channel to transport the drug into the cell. To address this issue, it is suggested to use TRPV1 ion channels as a potential target for drug release by nano-DDSs since these channels are overexpressed in cancer cells and allow the permeation of large cationic molecules. Considering these facts, this work presents three studies using molecular dynamics simulations of a human TRPV1 (hTRPV1) channel built here. The purpose of these simulations is to study the interaction between a single-wall carbon nanotube (SWCNT) and hTRPV1, and the diffusion of doxorubicin (DOX) across hTRPV1 and across a POPC lipid membrane. The first study shows an attractive potential between the SWCNT surface and hTRPV1, tilting the adsorbed SWCNT. The second study shows low diffusion probability of DOX across the open hTRPV1 due to a high free energy barrier. Although, the potential energy between DOX and hTRPV1 reveals an attractive interaction while DOX is inside hTRPV1. These results suggest that if the channel is dilated, then DOX diffusion could occur. The third study shows a lower free energy barrier for DOX across the lipid membrane than for DOX across hTRPV1. Taking into account the results obtained, it is feasible to design novel nano-DDSs based on SWCNTs to accomplish controlled drug release into cells using as translocation pathway, the hTRPV1 ion channel. PMID:26872481

  16. Remote electron and drug therapy of patients with malignant maxillofacial tumors

    International Nuclear Information System (INIS)

    The authors present an analysis of early and delayed results of concomitant radio- and chemo therapy of local and general reactions in 154 patients with advanced rhinal tumors, with advanced tumors of the accessory nasal sinus, of rhino-and stomatopharynx, of the mucous membrane of the oral cavity and parotid salivary gland. Complete tumor regression was obtained in 74 patient (48%), partial in 53 (34.4%). The best early effect has been revealed in patients with tumors of the rhino- and stomatopharynx. The total 3-and 5-year survival rates were 45% and 34.3%, respectively. Adjunctive cytostatic chemo therapy does not result in the increased number and severity of local and general reactions, and certain peculiarities in the dose distribution make fast electrons more preferable for radiotherapy of maxillofacial tumors

  17. Two cases of atrial flutter with fetal hydrops: successful fetal drug therapy.

    OpenAIRE

    Won, H. S.; Lee, I. S.; Yoo, H. K.; Yoo, S. J.; Ko, J K; Lee, P R; A. Kim; Mok, J. E.

    1998-01-01

    We describe two cases of fetal atrial flutter associated with severe fetal hydrops which were unresponsive to digoxin but were successfully treated with flecainide acetate. Two cases of fetal atrial flutter were identified in fetuses with severe fetal hydrops on 3rd trimester ultrasonogram(28 weeks' gestation and 30 weeks' gestation). Following failed digoxin monotherapy, flecainide acetate was added to digoxin. On the 7th day and 13th day after combined therapy, fetal heart rate converted to...

  18. Induced pluripotent stem cells, new tools for drug discovery and new hope for stem cell therapies

    OpenAIRE

    Shi, Yanhong

    2009-01-01

    Somatic cell nuclear transfer or therapeutic cloning has provided great hope for stem cell-based therapies. However therapeutic cloning has been experiencing both ethical and technical difficulties. Recent breakthrough studies using a combination of four factors to reprogram human somatic cells into pluripotent stem cells without using embryos or eggs led to an important revolution in stem cell research. Comparative analysis of human induced pluripotent stem cells and human embryonic stem cel...

  19. Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

    OpenAIRE

    Roberto Manfredi; Leonardo Calza; Vincenzo Colangeli; Nicola Dentale; Gabriella Verucchi

    2012-01-01

    A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and fin...

  20. A review of technology-assisted self-help and minimal contact therapies for drug and alcohol abuse and smoking addiction: is human contact necessary for therapeutic efficacy?

    Science.gov (United States)

    Newman, Michelle G; Szkodny, Lauren E; Llera, Sandra J; Przeworski, Amy

    2011-02-01

    Technology-based self-help and minimal contact therapies have been proposed as effective and low-cost interventions for addictive disorders, such as nicotine, alcohol, and drug abuse and addiction. The present article reviews the literature published before 2010 on computerized treatments for drug and alcohol abuse and dependence and smoking addiction. Treatment studies are examined by disorder as well as amount of therapist contact, ranging from self-administered therapy and predominantly self-help interventions to minimal contact therapy where the therapist is actively involved in treatment but to a lesser degree than traditional therapy and predominantly therapist-administered treatments involving regular contact with a therapist for a typical number of sessions. In the treatment of substance use and abuse it is concluded that self-administered and predominantly self-help computer-based cognitive and behavioral interventions are efficacious, but some therapist contact is important for greater and more sustained reductions in addictive behavior. PMID:21095051

  1. Dual antiplatelet therapy, drug-eluting stents and bioresorbable vascular scaffolds: Evolutionary perspectives.

    Science.gov (United States)

    Albuquerque, Felipe N; Bortnick, Anna; Iqbal, Javaid; Ishibashi, Yuki; Stone, Gregg W; Serruys, Patrick W

    2016-04-01

    Dual antiplatelet therapy reduces the risk of myocardial infarction, stent thrombosis, and cardiovascular mortality after percutaneous coronary intervention, but the optimal duration of therapy remains unclear. Stent thrombosis, one of the most feared complications of coronary intervention, is associated with high mortality and morbidity and is related in part to technical and patient-specific factors. Advances in device technology and better understanding of the pathophysiology of stent thrombosis have reduced the frequency of this devastating complication. Bioresorbable vascular scaffolds possess a number of advantageous features and are currently undergoing active investigation. Bioresorbable vascular scaffolds have been demonstrated to restore physiologic vasomotion, allow for late lumen enlargement, and upon full resorption remove the nidus for very late polymer reactions and resolve concerns of stent malapposition and side branch jailing. Based on the results from recent large-scale randomized trials, the optimal duration of dual antiplatelet therapy may depend on the choice of device type, as well as the individual patient risk of ischemic versus hemorrhagic complications. © 2015 Wiley Periodicals, Inc. PMID:26257287

  2. Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome

    DEFF Research Database (Denmark)

    Diness, Thomas G; Yeh, Yung-Hsin; Qi, Xiao Yan; Chartier, Denis; Tsuji, Yukiomi; Hansen, Rie S; Olesen, Søren-Peter; Grunnet, Morten; Nattel, Stanley

    2008-01-01

    AIMS: Impaired repolarization in cardiac myocytes can lead to long QT syndrome (LQTS), with delayed repolarization and increased susceptibility to Torsades de Pointes (TdP) arrhythmias. Current pharmacological treatment of LQTS is often inadequate. This study sought to evaluate the antiarrhythmic...... effect of a novel compound (NS1643) that activates the rapid delayed-rectifier K+ current, I(Kr), in two rabbit models of acquired LQTS. METHODS AND RESULTS: We used two clinically relevant in vivo rabbit models of TdP in which we infused NS1643 or vehicle: (i) three-week atrioventricular block with...... ventricular bradypacing; (ii) dofetilide-induced I(Kr) inhibition in methoxamine-sensitized rabbits. In addition, we studied effects on ionic currents in cardiomyocytes with I(Kr) suppressed by bradycardia remodelling or dofetilide exposure. Bradypaced rabbits developed QT interval prolongation, spontaneous...

  3. HIV-1 primary drug resistance mutations in antiretroviral therapy-naïve patients in Istanbul, Turkey

    Directory of Open Access Journals (Sweden)

    F Tabak

    2012-11-01

    Full Text Available According to the official information of Turkish Ministry of Health of HIV/AIDS surveillance data, in the period 1985 to the end of 2011, there are 4826 HIV-1 infected cases in Turkey. However, there is no data available on the antiretroviral (ART drug resistance. The objective of this study was to determine primary drug resistance in HIV-1 infections in newly diagnosed, ART-naïve Turkish patients in Istanbul, Turkey. The study was carried out between June 2009 and June 2012 and 59 HIV-1-infected patients were included (gender; 52 male/7 female, age, median years (range; 37.9 (20–57, CD4+ T-cell count, median mm3 (range; 280 (3–813, HIV-RNA load, median IU/ml (range; 4.1 + E5 (2.6 + E3–2.9 + E6. For HIV-1 subtyping most widely known algorithm; the HIVdb-Stanford University genotypic resistance interpretation algorithm has been used. According to population-based sequencing of the reverse transcriptase and protease genes of HIV-1, the patients had pre-existing primary ART drug resistance mutations and were related to NRTIs (M41L, D67N, T215D, T215E, T215S, NNRTIs (V179D and PIs (I54V, V82A. The prevalence of overall primary ART drug resistance were 11.8% (7/59 in Turkish patients and according to NRTIs, NNRTIs and PIs drug groups were 10% (6/59, 1.7% (1/59 and 1.7% (1/59, respectively (in one patient has been either NRTIs and PIs resistance detected. The high prevalence of HIV-1 primary drug resistance in ART-naïve patients suggested the resistance testing must be an integral part of the management of HIV infection and the choice of first-line therapy regime should be guided by genotypic resistance interpretation in Turkey.

  4. Texosome-based drug delivery system for cancer therapy: from past to present

    International Nuclear Information System (INIS)

    Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Malfunction of the immune system, particularly in the tumor microenvironment, causes tumor growth and enhances tumor progression. Thus, cancer immunotherapy can be an appropriate approach to provoke the systemic immune system to combat tumor expansion. Texosomes, which are endogenous nanovesicles released by all tumor cells, contribute to cell-cell communication and modify the phenotypic features of recipient cells due to the texosomes’ ability to transport biological components. For this reason, texosome-based delivery system can be a valuable strategy for therapeutic purposes. To improve the pharmaceutical behavior of this system and to facilitate its use in medical applications, biotechnology approaches and mimetic techniques have been utilized. In this review, we present the development history of texosome-based delivery systems and discuss the advantages and disadvantages of each system

  5. Virus reactivation and intravenous immunoglobulin (IVIG) therapy of drug-induced hypersensitivity syndrome.

    Science.gov (United States)

    Kano, Yoko; Inaoka, Miyuki; Sakuma, Keiichi; Shiohara, Tetsuo

    2005-04-15

    Drug-induced hypersensitivity syndrome (DIHS) is a severe multi-organ system reaction caused by specific drugs. Many reports have revealed that human herpesvirus 6 (HHV-6) reactivation contributes to the development of DIHS. In addition, recent articles have shown that reactivation of other herpesviruses such as human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV), cytomegalovirus (CMV) might be also implicated in the development of DIHS. These observations suggest that not only HHV-6 but also other herpesvirses might reactivate from the latency and play an important role in the appearance of clinical manifestations of DIHS. Several patients with DIHS were treated with intravenous immunoglobulin (IVIG) in addition to systemic corticosteroids. The results have been encouraging although virus reactivation could not be suppressed. Although the pathomechanism of IVIG treatment in patients with DIHS remains unknown, the therapeutic effects of IVIG could be dependent, in part, on functional capabilities of anti-virus IgG contained in IVIG. PMID:15767030

  6. Herbal Remedy: An Alternate Therapy of Nonsteroidal Anti-Inflammatory Drug Induced Gastric Ulcer Healing

    Directory of Open Access Journals (Sweden)

    Ananya Chatterjee

    2014-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are one of the most commonly used therapeutic drug groups used worldwide for curing an array of health problems like pain, inflammation, cardiovascular complications, and many other diseases, but they may cause different side effects including gastroduodenal disorders. So, there is a growing interest and need to search for nontoxic, antiulcer formulations from medicinal plants to treat NSAIDs induced gastric ulcer. Extensive research has reported on many natural plants like Camellia sinensis, Phyllanthus emblica, Myristica malabarica, Piper betle, Picrorhiza kurroa, and so forth, and their active constituents reduced NSAIDs induced gastric ulcer via their antioxidative as well as immunomodulatory activity. Therefore, use of herbal formulations in daily life may prevent NSAIDs induced gastric ulceration and other side effects.

  7. Emergence of HIV-1 drug resistance mutations among antiretroviral-naïve HIV-1-infected patients after rapid scaling up of antiretroviral therapy in Thailand

    Directory of Open Access Journals (Sweden)

    Sungkanuparph Somnuek

    2012-03-01

    Full Text Available Abstract Background After rapid scaling up of antiretroviral therapy in HIV-1-infected patients, the data of primary HIV-1 drug resistance in Thailand is still limited. This study aims to determine the prevalence and associated factors of primary HIV-1 drug resistance in Thailand. Methods A prospective observational study was conducted among antiretroviral-naïve HIV-1-infected Thai patients from 2007 to 2010. HIV-1 subtypes and mutations were assayed by sequencing a region of HIV-1 pol gene. Surveillance drug resistance mutations recommended by the World Health Organization for surveillance of transmitted HIV-1 drug resistance in 2009 were used in all analyses. Primary HIV-1 drug resistance was defined as the presence of one or more surveillance drug resistance mutations. Results Of 466 patients with a mean age of 38.8 years, 58.6% were males. Risks of HIV-1 infection included heterosexual (77.7%, homosexual (16.7%, and intravenous drug use (5.6%. Median (IQR CD4 cell count and HIV-1 RNA were 176 (42-317 cells/mm3 and 68,600 (19,515-220,330 copies/mL, respectively. HIV-1 subtypes were CRF01_AE (86.9%, B (8.6 and other recombinants (4.5%. The prevalence of primary HIV-1 drug resistance was 4.9%; most of these (73.9% had surveillance drug resistance mutations to only one class of antiretroviral drugs. The prevalence of patients with NRTI, NNRTI, and PI surveillance drug resistance mutations was 1.9%, 2.8% and 1.7%, respectively. From logistic regression analysis, there was no factor significantly associated with primary HIV-1 drug resistance. There was a trend toward higher prevalence in females [odds ratio 2.18; 95% confidence interval 0.896-5.304; p = 0.086]. Conclusions There is a significant emergence of primary HIV-1 drug resistance in Thailand after rapid scaling up of antiretroviral therapy. Although HIV-1 genotyping prior to antiretroviral therapy initiation is not routinely recommended in Thailand, our results raise concerns about the

  8. High Density Lipoprotein Structural Changes and Drug Response in Lipidomic Profiles following the Long-Term Fenofibrate Therapy in the FIELD Substudy

    OpenAIRE

    Yetukuri, Laxman; Huopaniemi, Ilkka; Koivuniemi, Artturi; Maranghi, Marianna; Hiukka, Anne; Nygren, Heli; Kaski, Samuel; Taskinen, Marja-Riitta; Vattulainen, Ilpo; Jauhiainen, Matti; Oresic, Matej

    2011-01-01

    In a recent FIELD study the fenofibrate therapy surprisingly failed to achieve significant benefit over placebo in the primary endpoint of coronary heart disease events. Increased levels of atherogenic homocysteine were observed in some patients assigned to fenofibrate therapy but the molecular mechanisms behind this are poorly understood. Herein we investigated HDL lipidomic profiles associated with fenofibrate treatment and the drug-induced Hcy levels in the FIELD substudy. We found that fe...

  9. Hepatic Arterial Therapy with Drug-Eluting Beads in the Management of Metastatic Bronchogenic Carcinoma to the Liver: A Multi-Institutional Registry

    OpenAIRE

    Heba Fouad; Tiffany Metzger; Cliff Tatum; Ken Robbins; Martin, Robert C.G.

    2012-01-01

    Introduction. There has been limited information reported on the use of hepatic arterial therapy in liver dominant hepatic metastases arising from lung cancer. The aim of this study was to evaluate the safety and efficacy of hepatic arterial therapy in the treatment of liver dominant hepatic metastases arising from lung cancer. Methods. Thirteen patients underwent a total of 30 treatment sessions with Drug-Eluting Beads. Eight of the thirteen received only doxorubicin DEB (17 of the total tre...

  10. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    OpenAIRE

    Pauline Byakika-Kibwika; Mohammed Lamorde; Harriet Mayanja-Kizza; Saye Khoo; Concepta Merry; Jean-Pierre Van geertruyden

    2011-01-01

    Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemether-lumefantrine (AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucle...

  11. ZEB1 knockdown mediated using polypeptide cationic micelles inhibits metastasis and effects sensitization to a chemotherapeutic drug for cancer therapy

    Science.gov (United States)

    Fang, Shengtao; Wu, Lei; Li, Mingxing; Yi, Huqiang; Gao, Guanhui; Sheng, Zonghai; Gong, Ping; Ma, Yifan; Cai, Lintao

    2014-08-01

    Metastasis and drug resistance are the main causes for the failure in clinical cancer therapy. Emerging evidence suggests an intricate role of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in metastasis and drug resistance. The EMT-activator ZEB1 is crucial in malignant tumor progression by linking EMT-activation and stemness-maintenance. Here, we used multifunctional polypeptide micelle nanoparticles (NP) as nanocarriers for the delivery of ZEB1 siRNA and doxorubicin (DOX). The nanocarriers could effectively deliver siRNA to the cytoplasm and knockdown the target gene in H460 cells and H460 xenograft tumors, leading to reduced EMT and repressed CSC properties in vitro and in vivo. The complex micelle nanoparticles with ZEB1 siRNA (siRNA-NP) significantly reduced metastasis in the lung. When DOX and siRNA were co-delivered by the nanocarriers (siRNA-DOX-NP), a synergistic therapeutic effect was observed, resulting in dramatic inhibition of tumor growth in a H460 xenograft model. These results demonstrated that the siRNA-NP or siRNA-DOX-NP complex targeting ZEB1 could be developed into a new therapeutic approach for non-small cell lung cancer (NSCLC) treatment.Metastasis and drug resistance are the main causes for the failure in clinical cancer therapy. Emerging evidence suggests an intricate role of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in metastasis and drug resistance. The EMT-activator ZEB1 is crucial in malignant tumor progression by linking EMT-activation and stemness-maintenance. Here, we used multifunctional polypeptide micelle nanoparticles (NP) as nanocarriers for the delivery of ZEB1 siRNA and doxorubicin (DOX). The nanocarriers could effectively deliver siRNA to the cytoplasm and knockdown the target gene in H460 cells and H460 xenograft tumors, leading to reduced EMT and repressed CSC properties in vitro and in vivo. The complex micelle nanoparticles with ZEB1 siRNA (siRNA-NP) significantly reduced

  12. Light and drug dosimetry considerations in porphyrin precursor–based photodynamic therapy

    OpenAIRE

    2007-01-01

    This thesis concerns light and drug dosimetry for photodynamic cancer treatment – a treatment modality where a photosensitizer uses the energy of light to damage biological matter. Porphyrin precursors were used as prodrugs which are synthesized into photosensitizers inside cells. Human subjects were studied as a part of developing a treatment for non-melanotic skin cancer. A 3-hour application of a topical cream photosensitized the tumor tissue with good selectivity versus normal skin, wh...

  13. Efficiency of drug therapy in complex rehabilitation of patients in late recovery period of stroke

    Directory of Open Access Journals (Sweden)

    Dilshod Sagatov

    2011-03-01

    Full Text Available Clinical and neurological studies in 73 patients (44 men and 29 women with the consequences of ischemic stroke in late recovery period were performed. Dopplerographic and electroencephalographic parameters before and after the rehabilitation measures were examined. In this study, we assessed the therapeutic effect of nootropics in drug rehabilitation with the inclusion of Nootropil and Cavinton Forte in late stroke recovery period.

  14. Local drug delivery agents as adjuncts to endodontic and periodontal therapy

    OpenAIRE

    Puri, K; Puri, N

    2013-01-01

    Abstract In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiv...

  15. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy

    OpenAIRE

    Wang ZY; Chen M; Zhu LL; Yu LS; Zeng S.; Xiang MX; Zhou Q

    2015-01-01

    Zhi-Yu Wang,1 Meng Chen,1 Ling-Ling Zhu,2 Lu-Shan Yu,3 Su Zeng,3 Mei-Xiang Xiang,4 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, 3Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, 4Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Coprescribing...

  16. PDE 7 inhibitors: new potential drugs for the therapy of spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Irene Paterniti

    Full Text Available BACKGROUND: Primary traumatic mechanical injury to the spinal cord (SCI causes the death of a number of neurons that to date can neither be recovered nor regenerated. During the last years our group has been involved in the design, synthesis and evaluation of PDE7 inhibitors as new innovative drugs for several neurological disorders. Our working hypothesis is based on two different facts. Firstly, neuroinflammation is modulated by cAMP levels, thus the key role for phosphodiesterases (PDEs, which hydrolyze cAMP, is undoubtedly demonstrated. On the other hand, PDE7 is expressed simultaneously on leukocytes and on the brain, highlighting the potential crucial role of PDE7 as drug target for neuroinflammation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present two chemically diverse families of PDE7 inhibitors, designed using computational techniques such as virtual screening and neuronal networks. We report their biological profile and their efficacy in an experimental SCI model induced by the application of vascular clips (force of 24 g to the dura via a four-level T5-T8 laminectomy. We have selected two candidates, namely S14 and VP1.15, as PDE7 inhibitors. These compounds increase cAMP production both in macrophage and neuronal cell lines. Regarding drug-like properties, compounds were able to cross the blood brain barrier using parallel artificial membranes (PAMPA methodology. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with S14 and VP1.15, two PDE7 inhibitors, significantly reduced the degree of spinal cord inflammation, tissue injury (histological score, and TNF-α, IL-6, COX-2 and iNOS expression. CONCLUSIONS/SIGNIFICANCE: All these data together led us to propose PDE7 inhibitors, and specifically S14 and VP1.15, as potential drug candidates to be further studied for the treatment of SCI.

  17. Neutralizing Antibodies against Plasmodium falciparum Associated with Successful Cure after Drug Therapy

    Science.gov (United States)

    Goh, Yun Shan; Peng, Kaitian; Chia, Wan Ni; Siau, Anthony; Chotivanich, Kesinee; Gruner, Anne-Charlotte; Preiser, Peter; Mayxay, Mayfong; Pukrittayakamee, Sasithon; Sriprawat, Kanlaya; Nosten, Francois; White, Nicholas J.

    2016-01-01

    An effective antibody response can assist drug treatment to contribute to better parasite clearance in malaria patients. To examine this, sera were obtained from two groups of adult patients with acute falciparum malaria, prior to drug treatment: patients who (1) have subsequent recrudescent infection, or (2) were cured by Day 28 following treatment. Using a Plasmodium falciparum antigen library, we examined the antibody specificities in these sera. While the antibody repertoire of both sera groups was extremely broad and varied, there was a differential antibody profile between the two groups of sera. The proportion of cured patients with antibodies against EXP1, MSP3, GLURP, RAMA, SEA and EBA181 was higher than the proportion of patients with recrudescent infection. The presence of these antibodies was associated with higher odds of treatment cure. Sera containing all six antibodies impaired the invasion of P. falciparum clinical isolates into erythrocytes. These results suggest that antibodies specific against EXP1, MSP3, GLURP, RAMA, SEA and EBA181 in P. falciparum infections could assist anti-malarial drug treatment and contribute to the resolution of the malarial infection. PMID:27427762

  18. Berberine in type 2 diabetes therapy: a new perspective for an old antidiarrheal drug?

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2012-08-01

    Full Text Available Type 2 diabetes mellitus (T2DM and dysglycemia (impaired glucose tolerance and/or impaired fasting glucose are increasingly contributing to the global burden of disease. Despite the continued introduction of hypoglycemic drugs, intervention in diabetes and its related complications remains a major global medical problem. Traditional Chinese medicine offers a number of potential candidates for developing hypoglycemic drugs. Berberine (BER, an isoquinoline alkaloid extract, has been commonly used as an oral drug to treat gastroenteritis and diarrhea for more than 1400 years. Although the antidiabetic effect of berberine has been noted in diabetic patients and demonstrated diabetic animal models in the last decade, its use is not yet accepted in the general medical community, for two reasons: its mechanism of action remains to be determined, and its bioavailability is low. Therefore, characterization of its mechanism of action and enhancement of its bioavailability are most important and the subject of current investigations. Recent studies have also revealed beneficial effects of berberine on diabetic complications. In this review the antidiabetic mechanism of action of berberine, its effect on diabetic complications, and efforts to improve its bioavailability are summarized. These studies may lead to its wider use for the treatment of type 2 diabetes mellitus and its complications.

  19. GKAs for diabetes therapy: why no clinically useful drug after two decades of trying?

    Science.gov (United States)

    Matschinsky, Franz M

    2013-02-01

    Results of basic biochemical and physiological research, strongly endorsed by findings in human pathophysiology and genetics, had characterized the glucose phosphorylating enzyme glucokinase as a critical player in normal glucose homeostasis, diabetes mellitus, and hyperinsulinemic hypoglycemia, and identified the enzyme as a promising new drug target. R&D initiated in the early 1990s and directed at this target discovered glucokinase activators (GKAs) as a new class of potentially antidiabetic drugs. GKAs were characterized as nonessential allosteric activators that increase glucose affinity and V(max) of the enzyme, thus stimulating glucose metabolism in glucokinase expressing tissue, of foremost functional significance in the insulin producing pancreatic beta cells and the liver. The results of preclinical testing of GKAs by many pharmaceutical companies demonstrated uniformly high hypoglycemic efficacy in normal and diabetic animals. GKAs were also highly effective in Phase I trials in patients with type 2 diabetes mellitus (T2DM). However, results of a recent Phase II trial were less encouraging because patients developed hyperlipidemia and vascular hypertension, and the drug lost efficacy within several months. This outcome is prompting a reappraisal of the GKA strategy. In this opinion article, the 'pros and cons' of the strategy to use these compounds in diabetes management are critically reexamined and suggestions are made that might facilitate progress of GKA R&D that could still result in a novel antidiabetic medicine. PMID:23305809

  20. Pharmacogenomics In Drug Therapy And Interaction: The Role Of Cytochrome P450

    Directory of Open Access Journals (Sweden)

    Peter Pook

    2008-12-01

    Full Text Available Pharmacogenomics (or pharmacogenetics,the study of the effects of genetic differences on aperson’s response to drugs, can help in optimizing drugefficacy and minimizing adverse drug reactions.Interperson difference in drug metabolism is one of theimportant consequences of such genetic variation. Thisvariation is determined in part by mutations incytochrome P450 enzymes (CYPs. IMU is part of amajor collaborative research project in the area ofphamacogenetics and drug metabolism. Workingtogether with USM and UiTM, our group has, since2000, generated useful population database on geneticpolymorphism of various CYP isoforms. We havesuccessfully genotyped three major ethnic groups,Malay, Indian and Chinese for their allelic frequency ofimportant isoforms. These include CYP2D6, CYP2C9,CYP2C8 and CYP2A6. Data generated so farcollectively have contributed to our effort in mappingand constructing genomic database for Malaysianpopulation.Since early 2002, our research has been focusing ondeveloping in vitro methods in studying the functionalconsequences of genetic polymorphism of CYP enzymes.Using site-directed mutagenesis, CYP mutants, carryingnucleotide changes as reported in known alleles inhuman populations, were generated and expressed inE. coli system, and the expressed recombinant proteinswere characterized using enzyme assays to determinethe functional consequences of mutations. We haveestablished a series of HPLC (high performance liquidchromatography-based and fluorescence-based assaysto investigate CYP activities. Assays that have beendeveloped include tolbutamide methylhydroxylase,paclitaxel 6α-hydroxylase, dextromethorphanO-demethylation, testosterone 6β-hydroxylation andcoumarin 7-hydroxylase assays. These assays serve asactivity markers allowing comparison of catalyticactivities of mutant proteins generated. Another focusof our work is to use the developed assays as a screeningtool to investigate drug-herb interactions. This wasachieved

  1. A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops

    OpenAIRE

    Ward Lorrayne; Ipuge Yahya; Odhiambo Moses; Gross Isaac; Bishop David; Gordon Megumi; Sabot Kate; Sabot Oliver; Cohen Justin M; Mwita Alex; Goodman Catherine

    2010-01-01

    Abstract Background Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs), the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility – malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation ...

  2. Provider and clinic-level correlates of deferring antiretroviral therapy for people who inject drugs: a survey of North American HIV providers

    OpenAIRE

    Westergaard Ryan P; Ambrose Bridget K; Mehta Shruti H; Kirk Gregory D

    2012-01-01

    Abstract Background Injection drug users (IDUs) face numerous obstacles to receiving optimal HIV care, and have been shown to underutilize antiretroviral therapy (ART). We sought to estimate the degree to which providers of HIV care defer initiation of ART because of injection drug use and to identify clinic and provider-level factors associated with resistance to prescribing ART to IDUs. Methods We administered an Internet-based survey to 662 regular prescribers of ART in the United States a...

  3. Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release

    Science.gov (United States)

    Zhang, Jinfeng; Li, Shengliang; An, Fei-Fei; Liu, Juan; Jin, Shubin; Zhang, Jin-Chao; Wang, Paul C.; Zhang, Xiaohong; Lee, Chun-Sing; Liang, Xing-Jie

    2015-08-01

    The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and monitoring.The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a

  4. Development of a model based on oncolytic adenovirus loaded with L-carnosine as a drug delivery system for cancer therapy

    OpenAIRE

    Garofalo, Mariangela

    2015-01-01

    Oncolytic viruses are viruses that are able to replicate specifically and infect and destroy only tumor cells. Many clinical studies have shown that the oncolytic approach alone could not efficiently destroy the large tumor mass, thus by limiting an efficacy virotherapy. Combination of oncolytic adenoviruses (Ads) and chemotherapeutic drugs has shown promising therapeutic results due to the synergistic action of virus and drug and is considered as a potential approach for cancer therapy. In t...

  5. Observation on 105 Cases of Duodenal Bulbar Ulcer Treated by Combined Therapy of Catgut Embedding and Chinese Drugs

    Institute of Scientific and Technical Information of China (English)

    范兆金

    2001-01-01

    @@Duodenal bulbar ulcer is a frequently encountered disease. Clinically, it manifests itself by regular epigastric pain accompanied by belching and acid regurgitation, corresponding to epigastralgia and stomach distending pain in traditional Chinese medicine (TCM). Based on the TCM type-differentiation, the author has treated 105 cases of duodenal bulbar ulcer by the combined therapy of catgut embedding at point Zusanli (ST 36) and Chinese drugs with satisfactory results. A summary is as follows. Clinical Data 1. Case selection: The cases selected all had the clinical symptoms and signs of duodenal bulbar ulcer, and had been diagnosed by GI examination at this or other hospitals with no obvious therapeutic effects obtained after relevant treatment, and still symptoms and signs and repeated attacks of pain.

  6. Programs of radiation and drug therapy for lung metastases of Ewing's sarcoma in children

    International Nuclear Information System (INIS)

    As a result of total-local irradiation of the lung combined with polychemotherapy in patients with solitary metastases to the lungs, a 3-year survival in children was 52.7+-12.1%, after local irradiation of the lungs and chemotherapy 30+-11.8% of the patients. Combined treatment was Well tolerated by pediatric patients. The results of the stUdy have shown that radiation therapy of metastases of Ewing sarcoma to the lungs with simultaneoUs polychemotherapy does not disturb external respiratory function even in a later period, the clinical manifestations of lung radiation reactions were seldom observed

  7. Radioactive iodine therapy in a case of Graves' disease with allergy to antithyroid drugs (ATD) and propranolol

    International Nuclear Information System (INIS)

    Full text: This is a case of V.C., 56 year old, female, from Las Pinas City, Philippines, diagnosed as a case of Graves' disease. During the course of therapy, the patient had allergy to antithyroid drugs (ATDs) and beta blocker (Propranolol). She developed rashes all over the body, sparing the face the day after taking her ATDs as well as Propranolol, thus all medications were discontinued. Other options, such as RAI therapy and surgery, with their respective advantages and disadvantages were fully explained to the patient who then opted to undergo RAI therapy. In our institution, we usually compute the dose based on the size of the gland and radioactive Iodine-131 uptake measurements (RAIU) rather than using fixed doses. Thyroid scintigraphy and RAIU were done which revealed poorly visualized thyroid gland and markedly diminished 24-hour uptake but normal 4-hour uptake [RAIU 4 hour uptake: 26% (NV= 15-25%); 24 hour uptake: 6% (NV25-45%)]. * Note: Variations in normal uptake values compared to US are due to iodine deficiency still existing in some regions. Because of the very low 24-hour uptake, we reviewed the probable causes which can result in low uptake values. All causes were ruled out and the patient was advised to undergo two weeks of strict low-iodine diet prior to repeat thyroid scintigraphy and RAIU. Thereafter, the result of repeat study showed diffuse thyromegaly with elevated uptake values indicating rapid trapping and organification processes [RAIU 4 hour uptake: 82% (NV= 15-25%); 24 hour uptake: 68% (NV25-45%)]. The day after the study, the patient was given 10 mCi I-131 based on the estimated weight of the gland, rapid thyroid iodine turnover ('small pool') and 24-hour uptake. This was considered to be the highest allowable dose of RAI to decrease the probability of relapse and the need for re-treatment. Approximately 4 weeks after the therapy, the patient is noted to have responded satisfactorily to therapy with resolution of symptoms. (author)

  8. New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

    Science.gov (United States)

    Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

    2013-12-01

    There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension. PMID:24222656

  9. Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs

    Directory of Open Access Journals (Sweden)

    Vreeke Ed

    2007-07-01

    Full Text Available Abstract Background Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs, the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. Methods The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe. From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. Results Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1–1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum. There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania. Conclusion Additional studies are required to build a more robust methodology, and to assess current consumptions

  10. Awareness of doctors of health care and possible therapy methods for alcohol and drug dependant patients in Latvia

    Directory of Open Access Journals (Sweden)

    Dave V.

    2012-10-01

    Full Text Available Aim is to investigate the knowledge of Latvian doctors about addiction treatment and healthcare possibilities in Latvia, to compare which methods are the best known to physicians, and which are offered to addicted patients. Work material and methods. Questionnaire was developed by researchers themselves, it contains 14 questions (about demographical data, treatment methods and their application. 250 questionnaires were distributed, 158 (63, 2% were received. Results. Average age of participants – 43.7 years. 31,0% of respondents are psychiatrists, 13,3% – addiction specialists, 34,8% – other specialists (general practitioners, internists, health care doctors, neurologists and others, 12,0% – psychotherapists, 4,4% – surgeons, 1,9% – dentists and 1,9% – paediatricians. The best known were detoxification (98,2% and suggestion (892% methods. The least known methods for drug addicts were substitution therapy (73,4% and rehabilitation communities (73,4%. The most recommended treatment method was Minnesota programme – 108 (68,4% and detoxification 99 (62,7%, the least recommended – substitution therapy – 29 (18,5%. Conclusions. 17,1% of respondents do not meet patients with addiction problems, but 20,3% of respondents don’t recommend any of treatment methods. Although 73%-98% of respondents have information about treatment methods, only 18%-68% of respondents offer them.

  11. Effect of Neurohormonal Blockade Drug Therapy on Outcomes and Left Ventricular Function and Structure After Left Ventricular Assist Device Implantation.

    Science.gov (United States)

    Grupper, Avishay; Zhao, Yanjun M; Sajgalik, Pavol; Joyce, Lyle D; Park, Soon J; Pereira, Naveen L; Stulak, John M; Burnett, John C; Edwards, Brooks S; Daly, Richard C; Kushwaha, Sudhir S; Schirger, John A

    2016-06-01

    Neurohormonal blockade drug therapy (NHBDT) is the cornerstone therapy in heart failure (HF) management for promoting reverse cardiac remodeling and improving outcomes. It's utility in left ventricular assist device (LVAD) supported patients remains undefined. Sixty-four patients who received continuous flow LVAD at our institution were retrospectively reviewed and divided into 2 groups: no-NHBDT group (n = 33) received LVAD support only and NHBDT group (n = 31) received concurrent NHBDT based on the clinical judgment of the attending physicians. Cardiac remodeling (echocardiographic parameters and biomarkers) and clinical outcome (functional status, HF-related hospital readmissions, and mortality) data were collected. A statistically significant increase in ejection fraction, decrease in LV end-diastolic diameter index and LV mass index, and a sustained reduction in N-terminal pro B-type natriuretic peptide (NTproBNP) were observed in the NHBDT group at 6 months after LVAD implant (p improvement in New York Heart Association functional classification and 6-minute-walk distance throughout the study. The combined end point of cardiovascular death or HF hospitalization was significantly reduced in patients receiving NHBDT (p = 0.013) associated primarily with a 12.1% absolute reduction in HF-related hospitalizations (p = 0.046). In conclusion, NHBDT in LVAD-supported patients is associated with a significant reversal in adverse cardiac remodeling and a reduction in morbidity and mortality compared with LVAD support alone. PMID:27079215

  12. HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy

    OpenAIRE

    Santiago Avila-Ríos; Claudia García-Morales; Daniela Tapia-Trejo; Rita I Meza; Nuñez, Sandra M.; Leda Parham; Norma A Flores; Diana Valladares; Pineda, Luisa M.; Dixiana Flores; Roxana Motiño; Víctor Umanzor; Candy Carbajal; Wendy Murillo; Ivette Lorenzana

    2015-01-01

    Introduction We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. Methods 365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO ...

  13. Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time

    DEFF Research Database (Denmark)

    Gallwitz, B; Vaag, A; Falahati, A; Madsbad, S

    2010-01-01

    AIM: To investigate the onset of treatment effects over time observed for liraglutide in combination with oral antidiabetic drugs (OADs). METHODS: This analysis included patients from three phase 3, 26-week, randomised, double-blind, parallel-group trials. Prior to randomisation, patients underwent...... a run-in and titration period with metformin (Liraglutide Effect and Action in Diabetes-2, LEAD-2), glimepiride (LEAD-1) or metformin plus rosiglitazone (LEAD-4). Patients were then randomised to receive liraglutide (0.6, 1.2 or 1.8 mg once-daily), active comparator and/or placebo. For this analysis...

  14. Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies

    Directory of Open Access Journals (Sweden)

    Rishi Raj Rikhi

    2016-03-01

    Full Text Available Limited research exists regarding the most aggressive forms of hepatoblastoma. Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not only difficult to attain, but are challenging to characterize histologically. A community approach to educating parents and families of the need for donated tissue is necessary for scientists to have access to resources for murine models and drug discovery. Herein we describe the currently available resources, the today’s existing gaps in research, and the path to move forward for uniform cure of hepatoblastoma.

  15. Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma.

    Science.gov (United States)

    Raju, Kalidhindi Rama Satyanarayana; Ambhore, Nilesh S; Mulukutla, Shashank; Gupta, Saurabh; Murthy, Vishakantha; Kumar, M N Kiran; Madhunapantula, Subba Rao V; Kuppuswamy, Gowthamarajan; Elango, Kannan

    2016-02-01

    Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients. PMID:26643666

  16. A new Ukrainian drug 'Propes' as an accompanying means in cytostatic therapy for patients with malignant lymphomas

    International Nuclear Information System (INIS)

    One of the major impediments in the way of higher efficacy for treating malignant lymphomas lies, first and foremost, in the inhibition of haemopoiesis and depressed immunity. Current methods for treating malignant lymphomas (chemotherapy,irradiation) result in the depression of immunity which later on leads to bone marrow hypoplasia, higher risk of developing infectious and viral disease, faster metastasis and recurrence of the process. Therefore, the study of essentially novel means for effecting the tumor growth is utmost topicality. In view of the above it becomes evident that methods of immune correction should acquire a certain stance in the combined treatment for malignant lymphomas. Since 1991 till 1996 we conducted a clinical trial for the new Ukrainian drug 'Propes'. As a result of its use against the background of polychemotherapy the amount of peripheral blood leukocytes keeps to the initial levels during the whole course of treatment. Not a single case developed such a frequent complication of cytostatic therapy as leukopenia not only during chemotherapy, but also through the whole period of further irradiation. The number of NK cells following a treatment course with 'Propes' doubles. The use of 'Propes' during the lesion remission enables its prolongation. Thus, during the whole follow-up (i.e. 5 years) all patients receiving the drug in the course of remission retained a relapse-free course. (Full text)

  17. Somatic and recombinant monoclonal antibodies for the diagnosis and therapy of drug unresponsive tumors

    International Nuclear Information System (INIS)

    Multiple reasons can explain the lack of clinical efficacy of chemotherapy. Among these, the intrinsic or acquired multidrug resistance (MDR) phenotype of tumor cells remain the major obstacles of successful pharmacological treatment of cancer. To circumvent this problem we developed several strategies which include: 1.) isolation of human monoclonal antibodies to tumour-associated antigen using an innovative biotechnological approach; 2.) genetic construction and expression of immuno-competent fusion protein to deliver enzymatic activities to tumor tissues to convert relatively non-toxic prodrugs into more active chemotherapeutic agents; 3.) identification of new chemical compounds capable to revert the MDR phenotype of tumor cells thus rendering drug resistant cancer de novo susceptible to chemotherapy; 4.) development and pre-clinical assay of novel anti tumor compounds with a high therapeutic index and evading the drug efflux mechanisms of the MDR1-P-glycoprotein (MDR1-Pgp) and the multidrug resistance-associated protein 1 (MRP1)which are often regarded as the prototypes of the cell-based mechanisms of MDR and failure of chemotherapy

  18. Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy.

    Science.gov (United States)

    Giandhari, Jennifer; Basson, Adriaan E; Sutherland, Katherine; Parry, Chris M; Cane, Patricia A; Coovadia, Ashraf; Kuhn, Louise; Hunt, Gillian; Morris, Lynn

    2016-04-01

    Protease inhibitors (PIs) are used as a first-line regimen in HIV-1-infected children. Here we investigated the phenotypic consequences of amino acid changes in Gag and protease on lopinavir (LPV) and ritonavir (RTV) susceptibility among pediatric patients failing PI therapy. The Gag-protease from isolates from 20 HIV-1 subtype C-infected pediatric patients failing an LPV and/or RTV-based regimen was phenotyped using a nonreplicativein vitroassay. Changes in sensitivity to LPV and RTV relative to that of the matched baseline (pretherapy) sample were calculated. Gag and protease amino acid substitutions associated with PI failure were created in a reference clone by site-directed mutagenesis and assessed. Predicted phenotypes were determined using the Stanford drug resistance algorithm. Phenotypic resistance or reduced susceptibility to RTV and/or LPV was observed in isolates from 10 (50%) patients, all of whom had been treated with RTV. In most cases, this was associated with protease resistance mutations, but substitutions at Gag cleavage and noncleavage sites were also detected. Gag amino acid substitutions were also found in isolates from three patients with reduced drug susceptibilities who had wild-type protease. Site-directed mutagenesis confirmed that some amino acid changes in Gag contributed to PI resistance but only in the presence of major protease resistance-associated substitutions. The isolates from all patients who received LPV exclusively were phenotypically susceptible. Baseline isolates from the 20 patients showed a large (47-fold) range in the 50% effective concentration of LPV, which accounted for most of the discordance seen between the experimentally determined and the predicted phenotypes. Overall, the inclusion of thegaggene and the use of matched baseline samples provided a more comprehensive assessment of the effect of PI-induced amino acid changes on PI resistance. The lack of phenotypic resistance to LPV supports the continued use of

  19. HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Santiago Avila-Ríos

    Full Text Available We assessed HIV drug resistance (DR in individuals failing ART (acquired DR, ADR and in ART-naïve individuals (pre-ART DR, PDR in Honduras, after 10 years of widespread availability of ART.365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI individuals were identified using a multi-assay algorithm.PDR to any ARV drug was 11.5% (95% CI 8.4-15.2%. NNRTI PDR prevalence (8.2% was higher than NRTI (2.2% and PI (1.9%, p500 vs. <350 CD4+ T cells/μL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%. The most prevalent PDR mutations were M46IL (1.4%, T215 revertants (0.5%, and K103NS (5.5%. The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the ≥48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343. M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01, but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naïve individuals and between ART-naïve individuals.The global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.

  20. Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

    Directory of Open Access Journals (Sweden)

    Yan Feng

    2011-03-01

    Full Text Available Yan Feng1, Marc R Gastonguay2, Bruce G Pollock3,5, Ellen Frank3, Gail H Kepple4, Robert R Bies5,6,71Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Lawrenceville, NJ, USA; 2Metrum Institute, Tariffville, CT, USA; 3Department of Psychiatry, School of Medicine, 4Department of Depression Prevention, University of Pittsburgh, PA, USA; 5Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 6Division of Clinical Pharmacology, School of Medicine and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; 7Indiana Clinical Translational Research Institute, Indiana University School of Medicine, IN, USABackground: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs and ratio of individual predicted to observed concentration (Cipred/Cobs as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history.Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the “Depression: The search for treatment relevant phenotypes” study, was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram. Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history.Results: Simulations for those scenarios representing a known