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Sample records for monitoring therapeutic efficacy

  1. Efficacy, nephrotoxicity and ototoxicity of aminoglycosides, mathematically modelled for modelling-supported therapeutic drug monitoring

    NARCIS (Netherlands)

    Croes, Sander; Koop, Arjen H.; van Gils, Stephanus A.; Neef, Cees

    Therapeutic drug monitoring (TDM) of aminoglycosides has been a topic during the last thirty years. There is a tendency that – because of the once-daily regimen – TDM is considered not necessary anymore. Although once daily dosing has the potential for decreased toxicity, long-term usage can cause

  2. [Therapeutic drug monitoring of rufinamide].

    Science.gov (United States)

    Bentué-Ferrer, Danièle; Tribut, Olivier; Verdier, Marie-Clémence

    2012-01-01

    Rufinamide is a third-generation antiepileptic drug, available since early 2010 in France. It is indicated in combination therapy in the Lennox-Gastaut syndrome from the age of 4. It has orphan drug status. The bioavailability of rufinamide is high, but decreases with the dose and increases with food intake. Rufinamide is not metabolized by cytochromes but hydrolyzed by a carboxylesterase in an inactive carboxylic derivative. Elimination is mainly renal. The half-life varies from 6 to 10h. Although established from relatively few studies, exposure efficacy and exposure toxicity relationships are argued. A plasma concentration of 15 mg/L, obtained with a standard regimen, reduces the number of seizures of 25%. Few factors of intrinsic variability are described. There are few clinically significant pharmacokinetic interactions and they concern combinations with other antiepileptic drugs, especially valproate. Although there is no validated therapeutic range, the level of evidence for this therapeutic drug monitoring has been estimated at "possibly useful".

  3. [Therapeutic drug monitoring of stiripentol].

    Science.gov (United States)

    Verdier, Marie-Clémence; Tribut, Olivier; Bentué-Ferrer, Danièle

    2012-01-01

    Stiripentol is a third generation antiepileptic, marketed since 2007 under the name of Diacomit(®). It is indicated, always in combination, in the treatment of severe myoclonic epilepsy in infancy or Dravet syndrome. Its pharmacokinetics is not linear. It is a potent inhibitor of CYP3A4, 1A2 and 2C19 and increases the plasma concentrations of many other antiepileptic drugs. Without this being considered as a validated therapeutic range, the trough plasma concentrations at steady-state, corresponding to the usual doses are between 10 and 15 mg/L. The concentration-efficacy relationship is not established, but there is some evidence for a concentration-related toxicity. However, because of its non-linear kinetics, stiripentol should be a good candidate for therapeutic drug monitoring (TDM). Nonetheless, the current level of evidence for the advantage of TDM is "remains to be estimated".

  4. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to extended-in

  5. [Therapeutic drug monitoring of antimicrobials

    NARCIS (Netherlands)

    Mouton, J.W.; Aarnoutse, R.E.

    2014-01-01

    The importance of dose adjustments of antimicrobials based on measured concentrations in an individual ('therapeutic drug monitoring', TDM) is increasingly recognized. There are several reasons for this. First, there is a better understanding of the relationships between doses administered,

  6. Therapeutic Drug Monitoring of Lithium

    DEFF Research Database (Denmark)

    Mose, Tina; Damkier, Per; Petersen, Magnus

    2015-01-01

    BACKGROUND: Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark. METHODS: In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5......), and (3) serum from individual patients (n = 7), lithium was measured in 19 laboratories using 20 different instruments. The lithium concentrations were targeted by a reference laboratory. Ion-selective electrode (n = 5), reflective spectrophotometric (RSM, n = 5), and spectrophotometric (n = 10) methods...... of >12%. Seven of these instruments had a systematic positive or negative bias and more so at lower lithium concentrations. Three poorly calibrated instruments were found in the ion-selective electrode group, 3 in the spectrophotometric group, and 2 in the RSM group. The instruments using reflectance...

  7. [Therapeutic drug monitoring of clobazam].

    Science.gov (United States)

    Bentué-Ferrer, Danièle; Tribut, Olivier; Verdier, Marie-Clémence; Debruyne, Danièle

    2010-01-01

    Clobazam is a 1,5 benzodiazepine available in France since 1975, used in add-on with the other anticonvulsant drugs in the treatment of refractory epilepsies of child and adult and for the treatment of anxiety of adult. It is mainly metabolized in desmethylclobazam, or norclobazam, active metabolite, present in a concentration approximately eight times superior to that of the parent drug, but with an activity of the order of 20 to 40% of that of clobazam. Elimination half-life of clobazam is of 18 h while that of norclobazam is from 40 to 50 h. There is a large interindividual variability in the plasma concentrations. Furthermore, clobazam being prescribed in add-on with the other anticonvulsant drugs in resistant epilepsies, concentration-effect relationship is difficult to bring to light, since, in many studies, the patients who did not answer received the highest doses. Adverse reactions are moderated, appearing more often for the highest concentrations; also the phenomenon of tolerance seems more frequent in high concentrations. However, because of the kinetic interactions, a dosage of clobazam and norclobazam can be useful in certain cases. There is no validated therapeutic range, but the usual concentrations are in the range of 100-300 microg/L for the parent drug and about ten times more for the metabolite. The level of proof of the interest of the Therapeutic Drug Monitoring for this molecule is estimated in: rather useless.

  8. Therapeutic drug monitoring, a practical application

    NARCIS (Netherlands)

    Kees Neef, C.; Touw, D.J.

    2010-01-01

    Therapeutic Drug Monitoring (TDM) is an indispensable tool in therapeutic handling and medication safety. A definition of TDM is: Therapeutic drug monitoring is a system of quality assurance of a drug management system, aiming that the right drug is given tot the right patient in the right dose in o

  9. Therapeutic drug monitoring in neonates.

    Science.gov (United States)

    Pauwels, Steven; Allegaert, Karel

    2016-04-01

    Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Efficacy of intraoperative neurophysiological monitoring.

    Science.gov (United States)

    Fisher, R S; Raudzens, P; Nunemacher, M

    1995-01-01

    Intraoperative neurophysiological monitoring is of benefit in protecting tissue at risk for trauma or ischemia during surgical procedures. Monitoring modalities include EEG, computer processed EEG, somatosensory (SEP), auditory (BAEP), and visual evoked potentials (VEP), and cranial nerve monitoring. The efficacy of monitoring is controversial, because no properly controlled prospective study of outcome with and without monitoring has been done. The weight of evidence suggests that loss of spontaneous EEG and SEP correlate well with critical reductions of cerebral blood flow. Meta-analysis of series comprising 3,028 patients undergoing carotid endarterectomies shows that SEP deteriorated in 5.6% of cases, with 20% of these having postoperative deficits, but more might have had deficits if they had not been shunted. SEP monitoring can be useful in surgery affecting brain and cord vasculature. Monitoring is not indicated for routine lumbosacral spine surgery. BAEPs have predictive value for preservation of hearing after acoustic neuroma surgery, and other surgery near the brainstem. VEPs have been too variable to be of major use in the operating room. For neurophysiologic monitoring to be useful, it must be performed by an experienced team, and the surgeon must be willing to act on the findings. Under these circumstances, monitoring can reduce surgical complications in selected cases.

  11. CT spectral imaging for monitoring the therapeutic efficacy of VEGF receptor kinase inhibitor AG-013736 in rabbit VX2 liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Yan, Xiaopeng; Chai, Yaru; Chen, Yan; Gao, Jianbo; Pan, Yuanwei; Li, Shuai; Guo, Hua; Zhou, Yue [The First Affiliated Hospital of Zhengzhou University, The Department of Radiology, Zhengzhou, Henan Province (China)

    2017-03-15

    The aim of this study was to evaluate the value of computed tomography (CT) spectral imaging in assessing the therapeutic efficacy of a vascular endothelial growth factor (VEGF) receptor inhibitor AG-013736 in rabbit VX2 liver tumours. Twenty-three VX2 liver tumour-bearing rabbits were scanned with CT in spectral imaging mode during the arterial phase (AP) and portal phase (PP). The iodine concentrations(ICs)of tumours normalized to aorta (nICs) at different time points (baseline, 2, 4, 7, 10, and 14 days after treatment) were compared within the treated group (n = 17) as well as between the control (n = 6) and treated groups. Correlations between the tumour size, necrotic fraction (NF), microvessel density (MVD), and nICs were analysed. The change of nICs relative to baseline in the treated group was lower compared to the control group. A greater decrease in the nIC of a tumour at 2 days was positively correlated with a smaller increase in tumour size at 14 days (P < 0.05 for both). The tumour nIC values in AP and PP had correlations with MVD (r = 0.71 and 0.52) and NF (r = -0.54 and -0.51) (P < 0.05 for all). CT spectral imaging allows for the evaluation and early prediction of tumour response to AG-013736. (orig.)

  12. Therapeutic Drug Monitoring in the Treatment of Active Tuberculosis

    Directory of Open Access Journals (Sweden)

    Aylin Babalik

    2011-01-01

    Full Text Available Therapeutic drug monitoring ensures optimal dosing while aiming to reduce toxicity. However, due to the high costs and complexity of testing, therapeutic drug monitoring is not routinely used in the treatment of individuals with active tuberculosis, despite the efficacy demonstrated in several randomized trials. This study reviewed data spanning five years regarding the frequency of finding low drug levels in patients with tuberculosis, the dosing adjustments that were required to achieve adequate levels and the factors associated with low drug levels.

  13. Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models.

    Science.gov (United States)

    Xie, Bangwen; Stammes, Marieke A; van Driel, Pieter B A A; Cruz, Luis J; Knol-Blankevoort, Vicky T; Löwik, Martijn A M; Mezzanotte, Laura; Que, Ivo; Chan, Alan; van den Wijngaard, Jeroen P H M; Siebes, Maria; Gottschalk, Sven; Razansky, Daniel; Ntziachristos, Vasilis; Keereweer, Stijn; Horobin, Richard W; Hoehn, Mathias; Kaijzel, Eric L; van Beek, Ermond R; Snoeks, Thomas J A; Löwik, Clemens W G M

    2015-11-17

    Quantification of tumor necrosis in cancer patients is of diagnostic value as the amount of necrosis is correlated with disease prognosis and it could also be used to predict early efficacy of anti-cancer treatments. In the present study, we identified two near infrared fluorescent (NIRF) carboxylated cyanines, HQ5 and IRDye 800CW (800CW), which possess strong necrosis avidity. In vitro studies showed that both dyes selectively bind to cytoplasmic proteins of dead cells that have lost membrane integrity. Affinity for cytoplasmic proteins was confirmed using quantitative structure activity relations modeling. In vivo results, using NIRF and optoacoustic imaging, confirmed the necrosis avid properties of HQ5 and 800CW in a mouse 4T1 breast cancer tumor model of spontaneous necrosis. Finally, in a mouse EL4 lymphoma tumor model, already 24 h post chemotherapy, a significant increase in 800CW fluorescence intensity was observed in treated compared to untreated tumors. In conclusion, we show, for the first time, that the NIRF carboxylated cyanines HQ5 and 800CW possess strong necrosis avid properties in vitro and in vivo. When translated to the clinic, these dyes may be used for diagnostic or prognostic purposes and for monitoring in vivo tumor response early after the start of treatment.

  14. ECONOMIC ISSUES IN THERAPEUTIC DRUG MONITORING.

    Science.gov (United States)

    Petryszyn, Paweł; Wiela-Hojeńska, Anna

    2016-01-01

    The fact that resources for health care are limited has been found as a rationale for the development of pharmacoeconomics. Pharmacoeconomic analysis identifies, measures and compares the costs and the economic, clinical and humanistic outcomes of diseases, drug therapies and programmes directed to these diseases. As health care expenditures have escalated over the past decades, the number of its applications has increased. Taking into consideration outcome and economic issues and establishing their mutual relationship helps proper resource allocation. In the case of some effective and toxic drugs therapeutic drug monitoring has been proven to allow obtaining the desired clinical effects safely and thus to improve outcome. However, it requires the presence of clinical pharmacology or clinical pharmacy service within a hospital, which in turn is associated with some additional costs. This review sums up the results of pharmacoeconomic studies relevant to the use of therapeutic drug monitoring in case of the medicines for which it has been commonly performed so far.

  15. Therapeutic drug monitoring of amoxicillin and cloxacillin

    Institute of Scientific and Technical Information of China (English)

    OTRIBUT; PTATTEVIN; MVERDIER; YLETULZO; CMICELET; HALLAIN; DBENTURE-FERRER

    2004-01-01

    AIM: Beta-lactams (BL) are broad-spectrum antibiotics currently used in number of infectious diseases and some infections need high dose of antibiotics. BL studied here are eliminated rather quickly by the kidney. A renal insufficiency involves an increase in BL concentrations. Therapeutic drug monitoring could help in adapting the target concentration. METHODS: We developed a rapid (less than 20 min), sensitive, and specific HPLC method

  16. Therapeutic Efficacy Evaluation of Metronidazole and Some ...

    African Journals Online (AJOL)

    Erah

    Purpose: To develop a highly accurate molecular assay for evaluating the efficacy of metronidazole and some ... cause human infection [2]. They cause a ... culture is labor-intensive, and the result is not known for ... heat-inactivated Fetal Calf Serum (FCS), 100 ..... Mechanism of Amphotercin B resistance in L. donovani ...

  17. [Therapeutic monitoring: analytic, pharmacokinetic and clinical aspects].

    Science.gov (United States)

    Marquet, P

    1999-01-01

    This paper gives an overview of present aspects and future prospects of therapeutic drug monitoring (TDM). The main aims of TDM are to avoid therapeutic failures due to bad compliance or too low dose of a given drug, as well as adverse or toxic effects due to an excessive dose. The therapeutic drugs frequently monitored depend on the country, but are generally few. For some of these drugs or for others, only patients at risk or belonging to particular sub-populations for a given drug, need TDM. A pre-analytical management is necessary, comprising a correct information of the physician, concerning the nature of the sample to collect and the clinical data necessary to the interpretation, as well as their recording; the control of the sample routing and storing conditions. Nowadays, drug analyses are essentially performed using immunochemical techniques, rapid and easy to operate but limited to a small number of drugs, and chromatographic methods, more specific and adaptable to almost any therapeutic drug and financially and technically more and more accessible. The interpretation of analytical results is a most important part of TDM, which requires knowledge of clinical data, precise collection time, co-administered treatments, and to dispose of a previously defined therapeutic range or target concentration, adapted to the population to which the patient belongs; the limitations of the analytical technique used must also be considered. Clinical pharmacokinetics is a further step in the use of analytical results, allowing the prediction of an efficient dose and administration schedule in one step, using a limited number of blood samples and generally a Bayesian estimation algorithm, readily available through commercial software dedicated to a few drugs in different reference populations. The pharmacokinetic characteristics of different populations and the validation of bayesian estimation have also been published for a number of drugs, sometimes by pharmaceutical

  18. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  19. Understanding Music's Therapeutic Efficacy with Implications for Why Music Matters

    Science.gov (United States)

    Thram, Diane

    2015-01-01

    In this essay, I focus on how attention to music's therapeutic efficacy is important to the praxial music education philosophy espoused by Elliott and Silverman. I note, despite the use of the term praxis from Aristotle's philosophy dating back to antiquity, there is no mention in Music Matters 2 of what historical evidence tells us about how…

  20. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  1. Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Tiffany M. Mott

    2013-05-01

    Full Text Available Burkholderia mallei, the etiologic agent of glanders, are Category B select agents with biothreat potential, and yet effective therapeutic treatments are lacking. In this study, we showed that CpG administration increased survival, demonstrating protection in the murine glanders model. Bacterial recovery from infected lungs, liver and spleen was significantly reduced in CpG-treated animals as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected animals were infiltrated with higher levels of neutrophils and inflammatory monocytes, as compared to control animals. Employing the B. mallei bioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodal in vivo whole body imaging techniques. CpG-treatment increased recruitment of neutrophils to the lungs and reduced bioluminescent bacteria, correlating with decreased bacterial burden and increased protection against acute murine glanders. Our results indicate that protection of CpG-treated animals was associated with recruitment of neutrophils prior to infection and demonstrated, for the first time, simultaneous real time in vivo imaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimized in vivo imaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections.

  2. Therapeutic drug monitoring for imatinib: Current status and Indian experience.

    Science.gov (United States)

    Arora, Brijesh; Gota, Vikram; Menon, Hari; Sengar, Manju; Nair, Reena; Patial, Pankaj; Banavali, S D

    2013-07-01

    Imatinib is the current gold standard for treatment of chronic myeloid leukemia (CML). Recent pharmacokinetic studies have shown considerable variability in trough concentrations of imatinib due to variations in its metabolism, poor compliance, or drug-drug interactions and highlighted its impact on clinical response. A trough level close to 1000 ng/mL, appears to be correlated with better cytogenetic and molecular responses. Therapeutic Drug Monitoring (TDM) for imatinib may provide useful added information on efficacy, safety and compliance than clinical assessment alone and help in clinical decision making. It may be particularly helpful in patients with suboptimal response to treatment or treatment failure, severe or rare adverse events, possible drug interactions, or suspected nonadherence. Further prospective studies are needed to confirm relationship between imatinib plasma concentrations with response, and to define effective plasma concentrations in different patient populations.

  3. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    Directory of Open Access Journals (Sweden)

    Matthew D. Krasowski

    2010-06-01

    Full Text Available In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

  4. Therapeutic efficacy of Chymotrypsin in acute bovine mastitis

    Directory of Open Access Journals (Sweden)

    Marco Leal G

    2016-05-01

    Full Text Available Objective. To evaluate the therapeutic efficacy of a proteolytic drug “chymotrypsin” combined with beta-lactam antibiotics in cows with acute mastitis. Material and Methods. Fourteen cows with acute mastitis. Three cows were treated with a beta-latam antibiotic (BLA and the other eleven cows were treated with chymotrypsin plus beta-lactam antibiotic (C+BLA. The response was evaluated according to the semiological findings, somatic cell count (SCC and a microbiological culture. Results. There was a therapeutic efficacy comparing the pre and post treatment period (SCC reduction, p<0.01 and a reduction of clinical signs in 84.7% of treated quarters in the first day of treatment (C+BLA compared with (BLA. Conclusions. Chymotrypsin improves the treatment of acute mastitis when is combined with BLA, controlling the infected mammary glands, compared with the group treated only with amoxicilina and clavulanic acid.

  5. Glycosylation of therapeutic proteins: an effective strategy to optimize efficacy.

    Science.gov (United States)

    Solá, Ricardo J; Griebenow, Kai

    2010-02-01

    During their development and administration, protein-based drugs routinely display suboptimal therapeutic efficacies due to their poor physicochemical and pharmacological properties. These innate liabilities have driven the development of molecular strategies to improve the therapeutic behavior of protein drugs. Among the currently developed approaches, glycoengineering is one of the most promising, because it has been shown to simultaneously afford improvements in most of the parameters necessary for optimization of in vivo efficacy while allowing for targeting to the desired site of action. These include increased in vitro and in vivo molecular stability (due to reduced oxidation, cross-linking, pH-, chemical-, heating-, and freezing-induced unfolding/denaturation, precipitation, kinetic inactivation, and aggregation), as well as modulated pharmacodynamic responses (due to altered potencies from diminished in vitro enzymatic activities and altered receptor binding affinities) and improved pharmacokinetic profiles (due to altered absorption and distribution behaviors, longer circulation lifetimes, and decreased clearance rates). This article provides an account of the effects that glycosylation has on the therapeutic efficacy of protein drugs and describes the current understanding of the mechanisms by which glycosylation leads to such effects.

  6. Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy.

    Science.gov (United States)

    Gauthier, Angela C; Mattson, Richard H

    2015-07-01

    Clobazam is an oral 1,5-benzodiazepine used worldwide for the treatment of many types of epilepsies, although it is currently only approved for Lennox-Gastaut syndrome in the USA. This anticonvulsant and anxiolytic therapeutic has repeatedly demonstrated great efficacy and a high safety profile in refractory epilepsy as well as in a few monotherapy trials in both children and adults. Clobazam allosterically activates the GABAA receptor, and it binds less to subunits that mediate sedative effects than other benzodiazepines. It acts quickly, maintaining a therapeutic effect for a long duration due to its active metabolite, N-desmethylclobazam. Dosage is between 5 mg and 40 mg a day, depending on patient weight, efficacy, and tolerability. Efficacy tolerance has not been a problem in the best studies. Clobazam has provided many benefits to epileptic patients. It should be used by clinicians early as an adjuvant therapy in the treatment of refractory epilepsy and even considered as monotherapy in a broad spectrum of epilepsy syndromes.

  7. Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

    LENUS (Irish Health Repository)

    Lambert, J S

    2011-03-01

    The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.

  8. Biosensors and nanobiosensors for therapeutic drug and response monitoring.

    Science.gov (United States)

    McKeating, Kristy S; Aubé, Alexandra; Masson, Jean-Francois

    2016-01-21

    Therapeutic drug monitoring (TDM) is required for pharmaceutical drugs with dosage limitations or toxicity issues where patients undergoing treatment with these drugs require frequent monitoring. This allows for the concentration of such pharmaceutical drugs in a patient's biofluid to be closely monitored in order to assess the pharmacokinetics, which could result in an adjustment of dosage or in medical intervention if the situation becomes urgent. Biosensors are a class of analytical techniques competent in the rapid quantification of therapeutic drugs and recent developments in instrumental platforms and in sensing schemes, as well as the emergence of nanobiosensors, have greatly contributed to the principal examples of these sensors for therapeutic drug monitoring. Based on initial success stories, it is clear that (nano)biosensors could pave the way for therapeutic drug monitoring of many commonly administered drugs and for new drugs that will be introduced to the market allowing for safe and optimal dosing across a wide range of pharmaceuticals. In this review, we report on the recent developments in biosensing and nanobiosensing techniques and, focussing mainly on anti-cancer agents and antibiotics, we discuss the different classes of molecules upon which therapeutic drug monitoring has already been successfully applied. The potential contributions of (nano)biosensors are also reviewed for the emerging areas of therapeutic response monitoring, where markers are monitored to ensure compliance of a patient to a treatment and in the area of cellular response to therapeutic drugs in order to identify cytotoxic effects of drugs on cells or to identify patients responding to a drug.

  9. Evaluation on the therapeutic drug monitoring data of vancomycin and its efficacy and renel toxicity in elder patients%老年患者万古霉素血药浓度监测与疗效评估

    Institute of Scientific and Technical Information of China (English)

    曲丹; 陈愉; 谷秀; 徐小嫚

    2015-01-01

    Objective To evaluate the drug plasma concentration , clini-cal efficacy and renal toxicity of vancomycin .Methods The clinical da-ta ( basic disease , bacteriological results , the serum concentrations of vancomycin , clinical efficacy , renal toxicity and initial dose selection ) of 39 elder patients were retrospectively analyzed.Results The effective rate of vancomycin was 82.05%.Vancomycin trough concentration be-tween 10-20 mg · L-1 accounted for 48.12%.Among the 19 patients whose vancomycin trough concentrations were less than 10 mg · L-1 , 6 cases adjusted the dose , 2 cases ( 5.13%) had renal toxicity , but the creatinine returned to basal levels after vancomycin was reduced or stopped.Renal toxicity didn′t appear in 3 cases (7.69%) who had renal insufficiency before using vancomycin.When vancomycin was combined with etimicin and diuretics , renal toxicity didn′t appear.Conclusion The dose of vancomycin should be adjusted in elder pa-tients.We should monitor serum concentration of vancomycin to adjust its legitimately use.%目的:评估老年患者的万古霉素血药浓度、临床疗效及肾毒性。方法回顾性分析我院呼吸科用万古霉素并监测血药浓度的39例老年患者的临床资料。结果万古霉素的治疗有效率为82.05%;谷浓度在10~20 mg · L-1占48.12%,谷浓度<10 mg · L-1的19例患者中有6例进行了剂量调整,2例(5.13%)患者出现了肾毒性,万古霉素减量或停用后肌酸酐均恢复至基础水平。3例(7.69%)用药前肾功能不全的患者均未有肾毒性发生。万古霉素联用依替米星及利尿剂未发生肾毒性。结论老年患者用万古霉素时应调整剂量,并借助血药浓度的监测对万古霉素进行调整。

  10. Therapeutic efficacy of ozone in patients with diabetic foot.

    Science.gov (United States)

    Martínez-Sánchez, Gregorio; Al-Dalain, Saied M; Menéndez, Silvia; Re, Lamberto; Giuliani, Attilia; Candelario-Jalil, Eduardo; Alvarez, Hector; Fernández-Montequín, José Ignacio; León, Olga Sonia

    2005-10-31

    Oxidative stress is suggested to have an important role in the development of complications in diabetes. Because ozone therapy can activate the antioxidant system, influencing the level of glycemia and some markers of endothelial cell damage, the aim of this study was to investigate the therapeutic efficacy of ozone in the treatment of patients with type 2 diabetes and diabetic feet and to compare ozone with antibiotic therapy. A randomized controlled clinical trial was performed with 101 patients divided into two groups: one (n = 52) treated with ozone (local and rectal insufflation of the gas) and the other (n = 49) treated with topical and systemic antibiotics. The efficacy of the treatments was evaluated by comparing the glycemic index, the area and perimeter of the lesions and biochemical markers of oxidative stress and endothelial damage in both groups after 20 days of treatment. Ozone treatment improved glycemic control, prevented oxidative stress, normalized levels of organic peroxides, and activated superoxide dismutase. The pharmacodynamic effect of ozone in the treatment of patients with neuroinfectious diabetic foot can be ascribed to the possibility of it being a superoxide scavenger. Superoxide is considered a link between the four metabolic routes associated with diabetes pathology and its complications. Furthermore, the healing of the lesions improved, resulting in fewer amputations than in control group. There were no side effects. These results show that medical ozone treatment could be an alternative therapy in the treatment of diabetes and its complications.

  11. Therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia

    Directory of Open Access Journals (Sweden)

    Ekta Atul Thakkar

    2014-12-01

    Full Text Available Aim: The aim was to determine therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia. Materials and Methods: Patients (n=9 with acute onset of renal dysfunction or chronic patients with superimposed acute factor (component or patients with known chronic nature of the disease were dialyzed with Fresenius 4008S hemodialysis machine after jugular catheterization. Patients were randomly divided into two groups, one group (n=3 was dialyzed every day and second (n=4 was dialyzed on alternate days. The patients were evaluated for following parameters to compare the efficacy of the dialysis prescription: Urea reduction ratio (URR, creatinine reduction ratio (CRR, Kt/V, time averaged concentration of urea (TAC urea. Result and Discussion: Increasing both dialysis frequency and duration is the superior dialysis schedule. Patient dialyzed every day with total processed blood volume 1.79 L/Kg for 4 h 26 min/session had the lowest TAC of 36.82 mg/dl, thereby was considered it as a better prescription.

  12. Adherence to HIV therapeutic drug monitoring guidelines in The Netherlands

    NARCIS (Netherlands)

    Luin, M. van; Wit, F.W.; Smit, C.; Rigter, I.M.; Franssen, E.J.; Richter, C.; Kroon, F.; Wolf, F. de; Burger, D.M.

    2011-01-01

    BACKGROUND: Therapeutic drug monitoring (TDM) is recommended in several international HIV treatment guidelines. The adherence of clinicians to these recommendations is unknown. The authors evaluated the adherence to the Dutch TDM guideline of 2005. METHODS: From the ATHENA cohort study, three

  13. Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy.

    LENUS (Irish Health Repository)

    Else, L J

    2014-11-01

    Pregnant women experience physiological changes during pregnancy that can have a significant impact on antiretroviral pharmacokinetics. Ensuring optimal plasma concentrations of antiretrovirals is essential for maternal health and to minimize the risk of vertical transmission. Here we describe atazanavir\\/ritonavir (ATV\\/r) plasma concentrations in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM).

  14. Zin en onzin van bloedspiegelbepalingen : Therapeutic drug monitoring bij ouderen

    NARCIS (Netherlands)

    Touw, D.J.; Edelbroek, P.M.; De Vries, O.J.

    2000-01-01

    The goal of therapeutic drug monitoring (TDM) is to maximise the effect of drug therapy and to minimise toxicity. TDM is meaningful if on the one hand there is a relationship between the serum concentration of the drug and its effect and on the other hand there is no obvious relationship between dos

  15. Is there a role for therapeutic drug monitoring with codeine?

    Science.gov (United States)

    Kelly, Lauren E; Madadi, Parvaz

    2012-06-01

    Codeine is an old and commonly used analgesic agent for mild to moderate pain. It is the prototypical "prodrug" in that its analgesic effect is almost wholly dependent on its biotransformation to morphine, a process that is mediated by the polymorphic cytochrome P450 2D6 enzyme. As such, interindividual variability in codeine metabolism and response is a clinical reality, and there has been much progress in characterizing the genetic causes of this variability in diverse populations. Yet despite the potential for both life-threatening adverse reactions and lack of therapeutic effect, codeine is not commonly indicated for therapeutic drug monitoring. This review will discuss the relative role of pharmacogenetics and therapeutic drug monitoring in predicting and/or maintaining adequate and safe analgesia with codeine. The review will end on a discussion of how the marriage of these 2 fields may provide new insights into the mechanisms of codeine-induced toxicity and analgesia.

  16. Biomaterial constructs for delivery of multiple therapeutic genes: a spatiotemporal evaluation of efficacy using molecular beacons.

    Directory of Open Access Journals (Sweden)

    Jennifer C Alexander

    Full Text Available Gene therapy is emerging as a potential therapeutic approach for cardiovascular pathogenesis. An appropriate therapy may require multiple genes to enhance therapeutic outcome by modulating inflammatory response and angiogenesis in a controlled and time-dependent manner. Thus, the aim of this research was to assess the spatiotemporal efficacy of a dual-gene therapy model based on 3D collagen scaffolds loaded with the therapeutic genes interleukin 10 (IL-10, a potent anti-inflammatory cytokine, and endothelial nitric oxide synthase (eNOS, a promoter of angiogenesis. A collagen-based scaffold loaded with plasmid IL-10 polyplexes and plasmid eNOS polyplexes encapsulated into microspheres was used to transfect HUVECs and HMSCs cells.The therapeutic efficacy of the system was monitored at 2, 7 and 14 days for eNOS and IL-10 mRNA expression using RT-PCR and live cell imaging molecular beacon technology. The dual gene releasing collagen-based scaffold provided both sustained and delayed release of functional polyplexes in vitro over a 14 day period which was corroborated with variation in expression levels seen using RT-PCR and MB imaging. Maximum fold increases in IL-10 mRNA and eNOS mRNA expression levels occurred at day 7 in HMSCs and HUVECs. However, IL-10 mRNA expression levels seemed dependent on frequency of media changes and/or ease of transfection of the cell type. It was demonstrated that molecular beacons are able to monitor changes in mRNA levels at various time points, in the presence of a 3D scaffolding gene carrier system and the results complemented those of RT-PCR.

  17. Retrospective survey on therapeutic efficacy of Qigong in Korea.

    Science.gov (United States)

    Lee, Myeong Soo; Hong, Sung-Soo; Lim, Hyun-Ja; Kim, Hye-Jung; Woo, Won-Hong; Moon, Sun-Rock

    2003-01-01

    Qigong is a complementary intervention for preventing and curing disease, and protecting and improving health through regulation of body and mind. Recently, we have been studying the psychoneuroimmunological effects of Qigong on the promotion of health. However, there are not many studies on the therapeutic efficacy of Qigong on various symptoms in Korea, hence the need to survey the clinical efficacy of Qigong. To evaluate the impact of Qigong in health care we categorized its effectiveness on the basis of ten years of subjects' memoranda. Among the 768 subjects, the motivation for doing Qigong was mostly to attend to health problems (81.5%), and males were more likely to use Qigong than females. The most improved symptoms were associated with psychological and musculoskeletal problems. Furthermore 66.9% of subjects reported improvements of perceived physical health and 40.3% of perceived psychological health. Other symptoms reduced by Qigong were pain (43.1%), fatigue (22.1%), and insomnia (8.7%). Wound healing was also surveyed (n = 332), and 84% of respondents reported improvement in recovery time, 66.6% reported reduced inflammation after Qigong and 50.3% reported no scarring as compared to before. In addition, 59.9% of respondents reported an increase in resistance to the common cold after four months of Qigong. The limitation of the study is that it is a retrospective survey on the basis of trainees' experiences of Qigong. Although this may constitute a potential bias, the study despite its limitations does provide precious empirical evidence of the effectiveness of Qigong.

  18. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

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    Stefano Salmaso

    2013-01-01

    Full Text Available Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

  19. The Slaying of a Beautiful Hypothesis: The Efficacy of Counseling and the Therapeutic Process

    Science.gov (United States)

    Hauser, Mike; Hays, Danica G.

    2010-01-01

    Although the efficacy of counseling has been empirically linked to the therapeutic process, the emphasis in much of the literature remains on technique use. This article discusses 3 components of therapeutic efficacy (i.e., common factors, working alliance, and counselor attributes) and provides implications for counselors and counselor training.…

  20. [Urinary tract infections. Therapeutic failures and course monitoring (author's transl)].

    Science.gov (United States)

    Abdou, M A

    1979-10-19

    The proportion of reinfections and relapses in urinary tract infections amounts to about 35-70%. Hydrokinetic conditions (e.g. size of bladder, frequency of micturition, rate of multiplication of the pathogens, adhesiveness of bacteria) not seldom lead to a discrepancy between the in vivo response of the pathogen to the chemotherapeutic agent and the corresponding MIC determined in vitro. Ten causes for the therapeutic failure are discussed in greater detail. Monitoring the course in good time with due regard to the risks is essential. A scheme for microbiological monitoring investigations before beginning therapy, during treatment and after discontinuing the medicament, as well as for long term therapy is suggested.

  1. CEP biomarkers as potential tools for monitoring therapeutics.

    Directory of Open Access Journals (Sweden)

    Kutralanathan Renganathan

    Full Text Available BACKGROUND: Carboxyethylpyrrole (CEP adducts are oxidative modifications derived from docosahexaenoate-containing lipids that are elevated in ocular tissues and plasma in age-related macular degeneration (AMD and in rodents exposed to intense light. The goal of this study was to determine whether light-induced CEP adducts and autoantibodies are modulated by pretreatment with AL-8309A under conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a serotonin 5-HT1A receptor agonist. METHODS: Albino rats were dark adapted prior to blue light exposure. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours before light exposure for 6 h (3.1 mW/cm(2, λ=450 nm. Animals were sacrificed immediately following light exposure and eyes, retinas and plasma were collected. CEP adducts and autoantibodies were quantified by Western analysis or ELISA. RESULTS: ANOVA supported significant differences in mean amounts of CEP adducts and autoantibodies among the light + vehicle, light + drug and dark control groups from both retina and plasma. Light-induced CEP adducts in retina were reduced ~20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006 and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p = 0.004 by drug pretreatment. Following drug treatment, average CEP autoantibody titer in light exposed rats (n = 22 was unchanged from dark control levels, and ~20% (p = 0.046 lower than in vehicle-treated rats. CONCLUSIONS: Light-induced CEP adducts in rat retina and plasma were significantly decreased by pretreatment with AL-8309A. These results are consistent with and extend previous studies showing AL-8309A reduces light-induced retinal lesions in rats and support CEP biomarkers as possible tools for monitoring the efficacy of select therapeutics.

  2. Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting

    DEFF Research Database (Denmark)

    Hansen, Morten Rix; Kuhlmann, Ida Berglund; Pottegård, Anton

    2017-01-01

    Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we......, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements. This article is protected by copyright. All rights reserved....

  3. [Increasing dosage: a momentous proposition to improve therapeutic efficacy of traditional Chinese medicine].

    Science.gov (United States)

    Xiao, Xiao-He; Yan, Dan; Jin, Cheng; Zhao, Yan-Ling

    2008-02-01

    To explore a key approach for improving therapeutic efficacy of traditional Chinese medicine by means of increasing its dosage. The rationality, necessity and feasibility of this proposition were explained and verified by the retrospective and prospective analysis about the current situation of therapeutic efficacy of traditional Chinese medicine, the relationship between dosage and therapeutic efficacy of traditional Chinese medicine, the rationality of conventional dosage specification. The unremarkable therapeutic efficacy was the main reason of traditional Chinese medicine to be denounced frequently, which was heavily due to its low dosage. However, many cases showed excellent therapeutic efficacy if a big dosage was used. Compared with the clinical dosage of western medicine and curative dose of active substance from traditional Chinese medicine or crude drugs, the specification of the conventional dosage of traditional Chinese medicine failed to be rigorous and objective. The viewpoint of "Cooking pot size limitation" and "Human stomach size limitation" may be the bottleneck which restricted the increase of traditional dosage. In conclusion, to increase the dosage of traditional Chinese medicine and elucidate the relationship between dosage and therapeutic efficacy would be a momentous and essential method to improve the therapeutic efficacy of traditional Chinese medicine.

  4. Therapeutic efficacy of hydro-kinesiotherapy Programs in lumbar spondylosis

    Directory of Open Access Journals (Sweden)

    Ana-Maria BOTEZAN

    2015-12-01

    Full Text Available Lumbar spondylarthrosis is a degenerative disease that affects the joint structures of the lumbar spine. In the course of time, numerous studies on the role of hydro-kinesiotherapy in the treatment of lumbar spondylosis have been conducted. The aim of this research is motivated by the significantly high number of patients with chronic pain in the lumbar spine due to lumbar spondylosis, as well as by the negative impact on their quality of life through the impairment of the activities of daily living. The prospective longitudinal study was carried out at the Clinical Rehabilitation Hospital Cluj-Napoca. The study included 35 patients with chronic low back pain and mobility limitation in the lumbar spine. The patients were assigned to two groups: the study group formed by 20 patients and the control group consisting of 15 patients aged between 40-70 years. The treatment of the patients included in the study was performed over a two week period and consisted of a hydro-kinesiotherapy program, for the patients of the study group, the duration of a treatment session being 40 minutes. Both the subjects of the study group and of the control group also benefited from sedative massage of the lumbosacral spine, kinesiotherapy, laser therapy of the lumbar spine. The patients were evaluated using Schober’s test, the Visual Analogue Scale, the Oswestry index. These evaluation methods were applied to the patients of both groups at the beginning of the rehabilitation programs and after two weeks. The results of the study demonstrated the therapeutic efficacy of the medical rehabilitation programs that included hydro-kinesiotherapy programs. The patients of both groups had improvements through a decrease of lumbar pain, an increase in lumbar spine mobility, as well as in the patients’ ability to organize themselves in the activities of daily living. However, the patients of the study group, with a hydro-kinesiotherapy program performed for two weeks, had

  5. Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

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    Amine BENLMOUDEN

    2016-06-01

    Full Text Available Cardiac glycosides have been used for congestive heart failure and certain cardiac arrhythmias for more than 200 years. Despite the introduction of a variety of new classes of drugs for the management of heart failure, specifically angiotensin-converting enzyme (ACE inhibitors, b-adrenergic antagonists (bblockers, and the aldosterone antagonist spironolactone, digoxin continues to have an important role in long-term outpatient management. However, a narrow margin exists between therapeutic and toxic doses of digoxin, resulting in a high incidence of digoxin toxicity in clinical practice.A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. The clinical relevance of digoxin therapeutic monitoring is also proved but the SDC (Serum Digoxin Conentrations required for optimal clinical efficacy and acceptable toxicity remains controversial. In the last years, international guidelines recommend 1.2 ng/mL as acceptable high level.In this bibliographic synthesis, we aim to collect pertinent informations from MedLine database about exposure-effect relationship in order to assess the evidence level scientific of new digoxin therapeutic monitoring

  6. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2017-01-01

    2 Award Number: W81XWH-11-1-0548 TITLE: Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer 5b. GRANT NUMBER W81XWH-11-1...identification of these T cells will lead to downstream antigen discovery. 15. SUBJECT TERMS Breast cancer, immunotherapy, vaccine , antigens 16

  7. [Triazole antifungal agents: practice guidelines of therapeutic drug monitoring and perspectives in treatment optimization].

    Science.gov (United States)

    Scodavolpe, Simon; Quaranta, Sylvie; Lacarelle, Bruno; Solas, Caroline

    2014-01-01

    Antifungal triazole agents (fluconazole, voriconazole, itraconazole and posaconazole) are widely used for the management of invasive fungal infections (IFI). These drugs are indicated both for the prophylaxis and treatment of IFI, particularly in candidiasis and aspergillosis, major cause of mortality in immunocompromised patients. Due to a large interindividual pharmacokinetic variability leading to sub-therapeutic or toxic concentrations and to concentration-efficacy and/or -toxicity relationships, therapeutic drug monitoring (TDM) of antifungal triazole is fully justified. This review provides an overview of literature based data that confirm the usefulness of such TDM and its level of evidence as well as the practical guidelines for its implementation. In addition, we discuss the interest of new tools to improve the clinical management of IFI, such as genotyping tests optimizing initial voriconazole dosing regimen or the development of a new solid oral tablet of posaconazole improving its bioavailability and limiting absorption disorders.

  8. Drug choice and therapeutic drug monitoring in the management of canine primary epilepsy : continuing education

    Directory of Open Access Journals (Sweden)

    T. Vaughan

    1999-07-01

    Full Text Available Therapeutic drug monitoring is an underutilised resource in the management of canine primary epilepsy. Many of the anti-epileptic drugs, including phenobarbitone, have variable pharmacokinetic profiles in different dogs, with each individual animal showing variable rates of absorption, distribution, metabolism and excretion. This results in variable serumdrug concentrations with the same oral dose. Many clinicians interpret this situation as therapeutic failure and classify these patients as refractory to treatment. By measuring blood concentrations of drugs at appropriate times, it is possible to explain the efficacy or failure of treatment, and also to prevent serum concentrations from reaching toxic levels. By analysing paired samples, key pharmacokinetic parameters may be calculated for each patient and a profile for the disposition of the drug obtained. Individual optimal drug dosage can be calculated for each patient at little cost to the pet owner.

  9. Guidelines for therapeutic drug monitoring of vancomycin: a systematic review.

    Science.gov (United States)

    Ye, Zhi-Kang; Li, Can; Zhai, Suo-Di

    2014-01-01

    Despite the availability of clinical practice guidelines (CPGs) for therapeutic drug monitoring (TDM) of vancomycin, vancomycin serum concentrations still do not reach therapeutic concentrations in many patients. Thus, we sought to systematically review the quality and consistency of recommendations for an international cohort of CPGs regarding vancomycin TDM. PubMed, Embase, guidelines' websites and Google were searched for CPGs for vancomycin TDM. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREEII) instrument and data were independently extracted. Twelve guidelines were evaluated and the overall quality of guidelines for vancomycin TDM was moderate. The highest score was recorded in the domain of clarity of presentation, and the lowest score was recorded in the domain of rigor of development and stakeholder involvement. The specific recommendations for vancomycin TDM were moderately consistent and guidelines varied in trough concentration monitoring, frequency of TDM, and serum concentration targets. The overall guideline quality for vancomycin TDM was not optimal and effort is needed to improve guideline quality, especially in the domain of rigor of development and stakeholder involvement.

  10. Therapeutic efficacy and artemisinin resistance in northern Myanmar: evidence from in vivo and molecular marker studies.

    Science.gov (United States)

    Myint, Moe Kyaw; Rasmussen, Charlotte; Thi, Aung; Bustos, Dorina; Ringwald, Pascal; Lin, Khin

    2017-04-07

    In Myanmar, three types of artemisinin-based combination therapy (ACT) are recommended as first-line treatment of uncomplicated falciparum malaria: artemether-lumefantrine (AL), artesunate-mefloquine (AS + MQ), and dihydroartemisinin-piperaquine (DP). Resistance to both artemisinins and ACT partner drugs has been reported from the Greater Mekong Sub-region, and regular efficacy monitoring of the recommended ACT is conducted in Myanmar. This paper reports on results from studies to monitor the efficacy of the three forms of ACT in sentinel sites in northern Myanmar, and investigations of mutations in the Kelch13 (k13) propeller domain. Seven therapeutic efficacy studies were conducted in 2011-12 and 2014 in three sentinel sites in Myanmar (Tamu, Muse, Tabeikkyin). Three studies were done for the evaluation of AL (204 patients), two studies for AS + MQ (119 patients) and two studies for DP (147 patients). These studies were done according to 2009 standard WHO protocol. Polymorphisms in the k13 propeller domain were examined in dried blood spots collected on day 0. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28 for AL and on day 42 for DP and AS + MQ, corrected to exclude re-infection using polymerase chain reaction (PCR) genotyping. Safety data were collected through self-reporting. PCR-corrected ACPR was 97.2-100% for AL, 98.6-100% for AS + MQ and 100% for DP across the study sites and years. All studies found a prevalence of k13 mutations (>440) above 23% in the day-0 samples. The F446I mutation was the most common mutation, making up 66.0% of the mutations found. Seven out of nine day-3 positive patients were infected with k13 wild type parasites. The remaining two cases with day-3 parasitaemia had the P574L mutation. The efficacy of AL, AS + MQ and DP remains high in northern Myanmar despite widespread evidence of k13 mutations associated with delayed parasite clearance. This study showed that already in 2012

  11. Intravoxel Incoherent Motion Diffusion Weighted MR Imaging for Monitoring the Instantly Therapeutic Efficacy of Radiofrequency Ablation in Rabbit VX2 Tumors without Evident Links between Conventional Perfusion Weighted Images.

    Directory of Open Access Journals (Sweden)

    Ziyi Guo

    Full Text Available To investigate the intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI as a potential valuable marker to monitor the therapy responses of VX2 to radiofrequency ablation (RF Ablation.The institutional animal care and use committee approved this study. In 10 VX2 tumor-bearing rabbits, IVIM-DWI examinations were performed with a 3.0T imaging unit by using 16 b values from 0 to 800 sec/mm2. The true diffusion coefficient (D, pseudodiffusion coefficient (D* and perfusion fraction (f of tumors were compared between before and instantly after RF Ablation treatment. The differences of D, D* and f and conventional perfusion parameters (from perfusion CT and dynamic enhanced magnetic resonance imaging, DCE-MRI in the coagulation necrosis area, residual unablated area, untreated area, and normal control had been calculated by compared t-test. The correlation between f or D* with perfusion weighted CT including blood flow, BF (milliliter per 100 mL/min, blood volume, BV (milliliter per 100 mL/min, and capillary permeability-surface area, PMB (as a fraction or from DCE-MRI: transfer constant (Ktrans, extra-vascular extra-cellular volume fraction (Ve and reflux constant (Kep values had been analyzed by region-of-interest (ROI methods to calculate Pearson's correlation coefficients.In the ablated necrosis areas, f and D* significantly decreased and D significantly increased, compared with residual unblazed areas or untreated control groups and normal control groups (P < 0.001. The IVIM-DWI derived f parameters showed significant increases in the residual unablated tumor area. There was no significant correlations between f or D* and conventional perfusion parameters.The IVIM-DW derived f, D and D* parameters have the potential to indicate therapy response immediately after RF Ablation treatment, while no significant correlations with classical tumor perfusion metrics were derived from DCE-MRI and perfusion-CT measurements.

  12. Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis.

    Science.gov (United States)

    Zuur, Marlanka A; Bolhuis, Mathieu S; Anthony, Richard; den Hertog, Alice; van der Laan, Tridia; Wilffert, Bob; de Lange, Wiel; van Soolingen, Dick; Alffenaar, Jan-Willem C

    2016-05-01

    Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment.

  13. The low therapeutic efficacy of postoperative chest radiographs for surgical intensive care unit patients

    NARCIS (Netherlands)

    A. Kröner; E. van Iperen; J. Horn; J.M. Binnekade; P.E. Spronk; J. Stoker; M.J. Schultz

    2011-01-01

    Background. The clinical value of postoperative chest radiographs (CXRs) for surgical intensive care unit (ICU) patients is largely unknown. In the present study, we determined the diagnostic and therapeutic efficacy of postoperative CXRs for different surgical subgroups and related their efficacy t

  14. Therapeutic efficacy of the neuroprotective plant adaptogen in neurodegenerative disease (Parkinson's disease as an example).

    Science.gov (United States)

    Bocharov, E V; Ivanova-Smolenskaya, I A; Poleshchuk, V V; Kucheryanu, V G; Il'enko, V A; Bocharova, O A

    2010-11-01

    Therapeutic efficacy of the plant neuroprotector Phytomix-40 in Parkinson's disease was demonstrated. This preparation consists of the components from extracts of 40 plants, including some adaptogens (ginseng, eleutherococcus, Rhodiola rosea, etc.). The preparation normalized immune, antioxidant, and hormonal parameters in patients. The neuroprotective plant adaptogen can be used in complex therapy for Parkinson's disease for improving its efficacy.

  15. Advances in the therapeutic monitoring of vancomycin concentrations

    Directory of Open Access Journals (Sweden)

    Kristina Nadrah

    2011-08-01

    Full Text Available Vancomycin is a glycopeptide antibiotic used for treatment of infections caused by methicillinresistant Staphylococcus aureus (MRSA. During the last decade there have been reports of glycopeptide resistant strains of Staphylococcus aureus. In some cases there are heterogenous populations of glycopeptide-susceptible and resistant strains which cannot be differentiated by standard clinical microbiology methods, but cause treatment failure and cross-resistance to other antibiotics. In order to improve clinical success and diminish the occurence of resistance, vancomycin trough concentrations of 15–20 mg/L have been recommended. With such high trough concentrations there have been warnings and doubts about the nephro and ototoxicity of vancomycin. The review article describes new guidelines for therapeutic monitoring of vancomycin concentrations and the scientific background of the amendments. We discuss the pharmacokinetic and pharmacodynamic characteristics of vancomycin, its toxicity and the problem of resistance.

  16. Potential biomarkers for monitoring therapeutic response in patients with CIDP.

    Science.gov (United States)

    Dalakas, Marinos C

    2011-06-01

    Although the majority of patients with CIDP variably respond to intravenous immunoglobulin (IVIg), steroids, or plasmapheresis, 30% of them are unresponsive or insufficiently responsive to these therapies. The heterogeneity in therapeutic responses necessitates the need to search for biomarkers to determine the most suitable therapy from the outset and explore the best means for monitoring disease activity. The ICE study, which led to the first FDA-approved indication for IVIg in CIDP, has shown that maintenance therapy prevents relapses and axonal loss. In this paper, the multiple actions exerted by IVIg on the immunoregulatory network of CIDP are discussed as potential predictors of response to therapies. Emerging molecular markers, promising in identifying responders to IVIg from non-responders, include modulation of FcγRIIB receptors on monocytes and genome-wide transcription studies related to inflammatory mediators, demyelination, or axonal degeneration. Skin biopsies, Peripheral Blood Lymhocytes, CSF, and sera are accessible surrogate tissues for further exploring these molecules during therapies.

  17. Clinical outcomes of the inclusion of the therapeutic drug monitoring report in the electronic clinical record

    Directory of Open Access Journals (Sweden)

    Marina Sáez Belló

    2016-12-01

    Full Text Available Objectives: To assess the inclusion of the Therapeutic Drug Monitoring Report (TDMR in the Electronic Clinical Record (ECR. Method: An observational ambispective cohort study with a duration of 149 days: PRE (retrospective, 49 days with the TDMR printed in paper, and POST (prospective, 100 days with the TDMR included in the ECR. Exclusion criteria: Patients not hospitalized, applications for Therapeutic Drug Monitoring by Critical Care and Neonatal Units, as well as monitoring with an objective other than dose adjustment. Variables: Number of TDMRs prepared, number of patients admitted with TDMR, time of delay for treatment adjustment, defined as the number of adjustments made to the treatment within over or under 24 hours from the time of TDMR preparation, and medication errors (MEs associated with said delay, as well as the degree of acceptance of the TDMR. Results: 690 TDMRs were conducted in 391 patients, 339 in PRE (n = 206 and 351 in POST (n = 185. The number of treatment modifications made in under 24 hours increased from 73.9% in PRE to 87.3% in POST [RR = 1.2 (CI95% = 0.97-1.43. We identified 35 patients with ME, 9.7% of them in PRE and 8.1% in POST (RR = 0.84 (CI95% = 0.44-1.58]. The degree of acceptance of the pharmacist recommendation increased from 53.3% in PRE to 68.3% in POST [RR = 1.3 (CI95% = 1.02- 1.62]. Conclusions: The inclusion of the Therapeutic Drug Monitoring Report (TDMR in the Electronic Clinical Record increases the degree of acceptance of recommendations, and may reduce the delay in treatment modifications, reducing MEs and improving the process quality in terms of efficacy and safety

  18. Therapeutic Drug Monitoring of Everolimus: A Consensus Report.

    Science.gov (United States)

    Shipkova, Maria; Hesselink, Dennis A; Holt, David W; Billaud, Eliane M; van Gelder, Teun; Kunicki, Paweł K; Brunet, Mercè; Budde, Klemens; Barten, Markus J; De Simone, Paolo; Wieland, Eberhard; López, Olga Millán; Masuda, Satohiro; Seger, Christoph; Picard, Nicolas; Oellerich, Michael; Langman, Loralie J; Wallemacq, Pierre; Morris, Raymond G; Thompson, Carol; Marquet, Pierre

    2016-04-01

    In 2014, the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology called a meeting of international experts to provide recommendations to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice. EVR is a potent inhibitor of the mammalian target of rapamycin, approved for the prevention of organ transplant rejection and for the treatment of various types of cancer and tuberous sclerosis complex. EVR fulfills the prerequisites for TDM, having a narrow therapeutic range, high interindividual pharmacokinetic variability, and established drug exposure-response relationships. EVR trough concentrations (C0) demonstrate a good relationship with overall exposure, providing a simple and reliable index for TDM. Whole-blood samples should be used for measurement of EVR C0, and sampling times should be standardized to occur within 1 hour before the next dose, which should be taken at the same time everyday and preferably without food. In transplantation settings, EVR should be generally targeted to a C0 of 3-8 ng/mL when used in combination with other immunosuppressive drugs (calcineurin inhibitors and glucocorticoids); in calcineurin inhibitor-free regimens, the EVR target C0 range should be 6-10 ng/mL. Further studies are required to determine the clinical utility of TDM in nontransplantation settings. The choice of analytical method and differences between methods should be carefully considered when determining EVR concentrations, and when comparing and interpreting clinical trial outcomes. At present, a fully validated liquid chromatography tandem mass spectrometry assay is the preferred method for determination of EVR C0, with a lower limit of quantification close to 1 ng/mL. Use of certified commercially available whole-blood calibrators to avoid calibration bias and participation in external proficiency-testing programs to allow continuous cross

  19. Current practice of therapeutic drug monitoring of biopharmaceuticals in spondyloarthritis.

    Science.gov (United States)

    Medina, Frédéric; Placensia, Chamaida; Goupille, Philippe; Paintaud, Gilles; Balsa, Alejandro; Mulleman, Denis

    2017-04-04

    Treatment of spondyloarthritis (SpA) has greatly improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes due to the presence of anti-drug antibodies (ADAs). In some instances, clinicians may increase or taper the dose, depending on the clinical response. Besides the current clinical practice, a tailored strategy based on drug monitoring is emerging as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals for SpA is still unknown. In this literature review, we examined the most relevant articles dealing with the concentration-response relation, ADA detection, and pharmacokinetics in SpA treated with biopharmaceuticals. ADAs were associated with low or undetectable concentration of monoclonal antibodies. The relation between drug concentration and clinical response in SpA is debated, some studies showing an association and others not. Therefore, TDM of biopharmaceuticals for SpA requires a better understanding of the association among the pharmacokinetics, pharmacodynamics, and immunogenicity of these drugs.

  20. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy

    Science.gov (United States)

    Yang, Lei; Wang, Zheran; Wang, Ju; Jiang, Weihua; Jiang, Xuewei; Bai, Zhaoshi; He, Yunpeng; Jiang, Jianqi; Wang, Dongkai; Yang, Li

    2016-03-01

    Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared

  1. Therapeutic trials in lupus nephritis. Problems related to renal histology, monitoring of therapy and measures of outcome.

    Science.gov (United States)

    Balow, J E

    1981-01-01

    Approaches to treatment of lupus nephritis have been complicated by controversies in the definitions of the types of renal histology, the relevance of immunological and renal monitoring techniques as therapeutic guidelines, and lack of definitive clinical trials. It is suggested that demonstration of the efficacy of various therapeutic agents in clinical trials may be identified earlier by renal histological changes and/or assessment of drug toxicity compared to the time required for differences based on renal functional changes to emerge as ultimate measures of outcome.

  2. Anticonvulsant Mechanisms of Electroconvulsive Therapy and Relation to Therapeutic Efficacy.

    Science.gov (United States)

    Duthie, Ashleigh C; Perrin, Jennifer S; Bennett, Daniel M; Currie, James; Reid, Ian C

    2015-09-01

    Electroconvulsive therapy (ECT) is held to confer anticonvulsant effects, although the role of rise in seizure threshold upon clinical effect is uncertain. This study investigated the relationship in a large, consecutive, retrospective sample of patients receiving ECT in Aberdeen. We have tested the hypotheses of previous authors to further examine the relationship between seizure and therapeutic effect as well as discuss the potential underlying neurobiological mechanisms. All patients receiving ECT at the Royal Cornhill Hospital between 2000 and the end of 2008 were identified from the Scottish ECT Accreditation Network. Electroconvulsive therapy was administered twice weekly with a bifrontotemporal electrode placement using routine dosage schedules. Data were gathered from the Scottish ECT Accreditation Network and case notes regarding ECT course and clinical effect. The seizure threshold increased in 219 (94.4%) patients, stayed the same in 13 (5.6%) patients, and decreased in 0 patient (n = 232). No significant relationship was present between change in seizure threshold and change in Montgomery-Asberg Depression Rating Scale score (P = 0.39; Kendall τ b r = 0.047; n = 182), although responders did display greater increase in seizure threshold than nonresponders. Electroconvulsive therapy confers anticonvulsant effects in a consecutive sample of real-life patients. Neither initial seizure threshold nor magnitude of seizure threshold increase is a predictor of clinical response to ECT. A rise in seizure threshold is not essential for therapeutic effect but may represent an important marker of underlying neuronal state. The evidence reviewed in this article supports a link between neuroplastic effects of ECT and the evidenced rise in seizure threshold.

  3. Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

    OpenAIRE

    Brandes Ralf P; Janssen Wiebke; Cornitescu Teodora; Sydykov Akylbek; Dahal Bhola K; Luitel Himal; Kojonazarov Baktybek; Kosanovic Djuro; Davie Neil; Ghofrani Hossein A; Weissmann Norbert; Grimminger Friedrich; Seeger Werner; Schermuly Ralph T

    2011-01-01

    Abstract Background Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods Monocrotaline-injected male Sprague-Dawley rats were randomized and treated...

  4. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

    Science.gov (United States)

    Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.

    2017-01-01

    Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659

  5. The Therapeutic Efficacy of Domestic Violence Victim Interventions.

    Science.gov (United States)

    Hackett, Shannon; McWhirter, Paula T; Lesher, Susan

    2016-04-01

    A meta-analysis on domestic violence interventions was conducted to determine overall effectiveness of mental health programs involving women and children in joint treatment. These interventions were further analyzed to determine whether outcomes are differentially affected based on the outcome measure employed. To date, no meta-analyses have been published on domestic violence victim intervention efficacy. The 17 investigations that met study criteria yielded findings indicating that domestic violence interventions have a large effect size (d = .812), which decreases to a medium effect size when compared to control groups (d = .518). Effect sizes were assessed to determine whether treatment differed according to the focus of the outcome measure employed: (a) external stress (behavioral problems, aggression, or alcohol use); (b) psychological adjustment (depression, anxiety, or happiness); (c) self-concept (self-esteem, perceived competence, or internal locus of control); (d) social adjustment (popularity, loneliness, or cooperativeness); (e) family relations (mother-child relations, affection, or quality of interaction); and (f) maltreatment events (reoccurrence of violence, return to partner). Results reveal that domestic violence interventions across all outcome categories yield effects in the medium to large range for both internalized and externalized symptomatology. Implications for greater awareness and support for domestic violence treatment and programming are discussed.

  6. Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Amel Harzallah

    2015-01-01

    Full Text Available Anemia is a frequent complication in patients with chronic kidney disease. However, human recombinant erythropoietin (rHu-EPO has revolutionized the management of anemia in chronically dialyzed patients. Epomax ® is a new rHu-EPO alfa manufactured in Tunisia (Medis Laboratories. The aim of this study was to evaluate the efficacy and tolerance of Epomax ® in chronic hemodialysis (HD patients in a phase-III, multicenter, clinical trial. Fiftythree HD patients (mean age 47.7 ± 13 years who received a stable dose of rHu-EPO (Hemax ® , a rHu-EPO alfa manufactured by Biosidus Laboratories subcutaneously were switched to Epomax ® via the same route of administration. At baseline, the mean systolic pressure was 132 ± 18 mm Hg and the mean diastolic pressure was 79 ± 8 mm Hg. The mean blood hemoglobin was 10.2 g/dL and the median ferritin level was 667 ng/mL. After a follow-up of 43 days, the mean blood hemoglobin was 10.5 g/dL under the effect of Epomax ® . There was no significant difference in the mean hemoglobin levels between the treatments with both drugs. Few adverse events were reported during the study. We conclude that Epomax ® was effective at maintaining the hemoglobin levels at target concentrations and was well tolerated in HD patients.

  7. Reporter nanoparticle that monitors its anticancer efficacy in real time.

    Science.gov (United States)

    Kulkarni, Ashish; Rao, Poornima; Natarajan, Siva; Goldman, Aaron; Sabbisetti, Venkata S; Khater, Yashika; Korimerla, Navya; Chandrasekar, Vineethkrishna; Mashelkar, Raghunath A; Sengupta, Shiladitya

    2016-04-12

    The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.

  8. An audit of therapeutic drug monitoring of anticonvulsants.

    Science.gov (United States)

    Sharpe, P. C.; Morrow, J.; Trimble, E. R.

    1995-01-01

    An audit of therapeutic drug monitoring (TDM) of anticonvulsants was performed to assess both its use and misuse in the management of patients with epilepsy. Over a four week period all samples received for phenytoin, carbamazepine, sodium valproate and phenobarbitone assays were included in the audit. The aims were to establish the source of the specimens, the reasons for the requests and to ascertain what action, if any, would be taken when the result of the assay was provided. A total of 163 separate assays were performed over the four week period (43 phenytoin, 74 carbamazepine, 41 valproate, 5 phenobarbitone). Only 18.7% of all requests originated from the adult neurology department. The vast majority of tests had been ordered by junior medical staff (only 10% by consultants) and approximately 50% were 'routine' with no satisfactory clinical reason for the request offered. There was a tendency to manipulate prescribed doses on the basis of drug levels alone without taking the clinical picture into consideration. These results demonstrate a general ignorance, especially amongst junior medical staff, of the value of TDM of anticonvulsants, and reinforce the need for both an educative and interpretive service to be provided by the Chemical Pathology Department. PMID:8533181

  9. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia

    Directory of Open Access Journals (Sweden)

    Álvarez Tania

    2006-02-01

    Full Text Available Abstract Objective Evaluate the frequency of failure of eight treatments for non-complicated malaria caused by Plasmodium falciparum in patients from Turbo (Urabá region, El Bagre and Zaragoza (Bajo Cauca region, applying the 1998 protocol of the World Health Organization (WHO. Monotherapies using chloroquine (CQ, amodiaquine (AQ, mefloquine (MQ and sulphadoxine-pyrimethamine (SP, and combinations using chloroquine-sulphadoxine-pyrimethamine (CQ-SP, amodiaquine-sulphadoxine-pyrimethamine (AQ-SP, mefloquine-sulphadoxine-pyrimethamine (MQ-SP and artesunate-sulphadoxine-pyrimethamine (AS-SP, were examined. Methodology A balanced experimental design with eight groups. Samples were selected based on statistical and epidemiological criteria. Patients were followed for 21 to 28 days, including seven or eight parasitological and clinical evaluations, with an active search for defaulting patients. A non-blinded evaluation of the antimalarial treatment response (early failure, late failure, adequate response was performed. Results Initially, the loss of patients to follow-up was higher than 40%, but the immediate active search for the cases and the monetary help for transportation expenses of patients, reduced the loss to 6%. The treatment failure was: CQ 82%, AQ 30%, MQ 4%, SP 24%, CQ-SP 17%, AQ-SP 2%, MQ-S-P 0%, AS-SP 3%. Conclusion The characteristics of an optimal epidemiological monitoring system of antimalarial treatment response in Colombia are discussed. It is proposed to focus this on early failure detection, by applying a screening test every two to three years, based on a seven to 14-day follow-up. Clinical and parasitological assessment would be carried out by a general physician and a field microscopist from the local hospital, with active measures to search for defaulter patients at follow-up.

  10. Temozolomide: The evidence for its therapeutic efficacy in malignant astrocytomas

    Directory of Open Access Journals (Sweden)

    Ayman I Omar

    2009-06-01

    Full Text Available Ayman I Omar1, Warren P Mason21Department of Medicine, Princess Margaret Hospital and the University of Toronto, Toronto, Ontario, Canada; 2Department of Medicine, University of Toronto, Toronto, Ontario, CanadaIntroduction: Malignant gliomas are a heterogeneous group of primary central nervous system neoplasms that represent less than 2% of all cancers yet carry a significant burden to society. They are frequently associated with considerable and progressive neurological disability and are ultimately intractable to all forms of treatment. Temozolomide (TMZ is a new second generation DNA alkylating agent that has become part of malignant astrocytoma management paradigms because of its proven efficacy, ease of administration, and favorable toxicity profile. Aims: To review the role of TMZ in the management of malignant astrocytomas (World Health Organization grades III and IV including newly diagnosed (n and recurrent (r anaplastic astrocytomas (AA and glioblastomas.Evidence review: A series of pivotal clinical trials have established a role for TMZ in the treatment of malignant astrocytomas. A large phase II trial examining the role of TMZ in rAA showed a response rate of 35%, and a 6-month progression-free survival of 46%. This led to the accelerated approval of TMZ by the FDA and the EU for the treatment of rAA. Evidence for a role of TMZ in nAA is currently limited but research is ongoing in this area. The role of TMZ in the management of glioblastoma at the time of recurrence (rGBM is less impressive but evidence for its activity was demonstrated in two large phase II trials that led to the approval of TMZ for this indication in Europe and Canada but not in the US. A recent large prospective randomized phase III trial showed that the addition of TMZ during and after radiation therapy (RT in newly diagnosed (nGBM patients prolonged median overall survival by 2.5 months; perhaps more importantly, the 2-year survival rate for patients

  11. Generalization of Therapeutic Changes in Agoraphobia: The Role of Perceived Self-Efficacy.

    Science.gov (United States)

    Williams, S. Lloyd; And Others

    1989-01-01

    Investigated extent and mechanisms of therapeutic generalization across distinct areas of agoraphobic dysfunction among 27 severe agoraphobics. Analysis of possible cognitive mechanisms revealed that perceived self-efficacy accurately predicted treatment and transfer effects even when alternative factors were held constant. Agoraphobia appears to…

  12. Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

    Directory of Open Access Journals (Sweden)

    Dev Vas

    2009-05-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL, a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required. Methods One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers msp-1 and msp-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in pfmdr1 was also carried out in the samples obtained from patients before and after the treatment. Results The PCR corrected cure rates were high at both the sites viz. 100% (n = 53 in Assam and 98.6% (n = 71 in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91 and 184 (91.3%, n = 91 of pfmdr1 gene. Conclusion AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria

  13. NON INVASIVE THERAPEUTIC DRUG MONITORING OF PROPRANOLOL HYDROCHLORIDE BY REVERSE IONTOPHORESIS

    OpenAIRE

    Saini Vipin; Nair Anroop; Goel Ankit

    2012-01-01

    Therapeutic drug monitoring (TDM) is highly required for drugs possessing narrow therapeutic index as a slight variation in the therapeutic range could result in no or low clinical efficiency or causes significant side effects or high risk of toxicity. In recent days, reverse iontophoresis technique has been attempted for the non invasive drug monitoring. Typically, it applies a low electric current through a pair of skin electrodes to promote the transport of both charged and neutral molecul...

  14. Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

    LENUS (Irish Health Repository)

    Lambert, J S

    2012-02-01

    OBJECTIVES: The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. METHODS: Women were enrolled in the study who were receiving the LPV\\/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS\\/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test). RESULTS: Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV\\/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells\\/muL and 8724 (<50-267408) HIV-1 RNA copies\\/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng\\/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first\\/second [3525 (2823-4227) ng\\/mL; n=16] and third [3346 (2813-3880) ng\\/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng\\/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng\\/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV\\/r tablet is appropriate during pregnancy

  15. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions

    Directory of Open Access Journals (Sweden)

    Gina M Graziani

    2015-11-01

    Full Text Available Introduction: The development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART, would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates. Discussion: This review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy. Conclusions: Given the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of

  16. Biomarkers for monitoring efficacy of bioremediation by microbial inoculants

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, J.K.; Elvang, A.M. [Stockholm University (Sweden). Arrhenius Laboratories for Natural Sciences; Bjorklof, K.; Jorgensen, K.S. [Finnish Environment Institute, Helsinki (Finland). Research Laboratory

    2000-07-01

    Bioaugmentation of contaminated sites with microbes that are adapted or genetically engineered for degradation of specific toxic compounds is an area that is currently being explored as a clean-up option. Biomarkers have been developed to track the survival and efficacy of specific bacteria that are used as inocula for bioremediation of contaminated soil. Examples of biomarkers include the Iuc gene, encoding firefly luciferase and the gfp gene, encoding the green fluorescent protein (GFP). The luc gene was used to tag different bacteria used for bioremediation of gasoline or chlorophenols. The bacteria were monitored on the basis of luciferase activity in cell extracts from soil. The gfp gene was also used to monitor bacteria during degradation of chlorophenol in soil, based on fluorescence of the GFP protein. Other biomarkers can also be used for monitoring of microbial inocula used for bioaugmentation of contaminated sites. The choice of biomarker and monitoring system depends on the particular site, bacterial strain and sensitivity and specificity of detection required. (author)

  17. Trichogram To Monitor Therapeutic Benefit In Hair Loss

    Directory of Open Access Journals (Sweden)

    Uppal Monica

    2004-01-01

    Full Text Available Trichogram is a method of quantifying hair. We report 3 cases of diffuse hair loss of varying etiology in whom the improvement after therapeutic intervention could be objectively documented using trichogram.

  18. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy

    Directory of Open Access Journals (Sweden)

    Fegert Jörg M

    2009-04-01

    Full Text Available Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

  19. Prophylactical and therapeutical efficacy of Tiamuline in mycoplasmosis of chickens and turkeys.

    Science.gov (United States)

    Stipkovits, L; Laber, G; Schultze, E

    1977-07-01

    To evaluate efficacy of Tiamuline in mycoplasmosis of chickens and turkeys under controlled field conditions 2 prophylactical and 3 therapeutical trials were conducted. The compound was administered via drinking water for 3 days in comparison to Tylosin tartrate. In both prophylactical and therapeutical tests, Tiamuline showed a superior efficiacy, as measured by clinical symptoms, pathological lesions and microbiological findings. Therefore, Tiamuline can be recommended for treatment of mycoplasmosis in chickens and turkeys in a dosage of 0.025% and in a dosage of 0.0125% for prophylaxis in flocks at risk.

  20. Value of therapeutic drug monitoring of MMF therapy in pediatric transplantation.

    Science.gov (United States)

    Filler, G

    2006-09-01

    Therapeutic drug monitoring (TDM) is desirable whenever the desired drug effect cannot be predicted from a given dose, or when it is necessary to find a balance between the efficacy and toxicity of the drug. Children and adolescents particularly benefit from TDM, because dosing requirements are often not studied in the same detail as in adults. Also, drug-drug interactions are frequent. The gold standard for assessment of drug exposure is the area-under-the-curve (AUC) for a full pharmacokinetic profile. TDM for mycophenolic acid (MPA) is less well established. Monitoring of trough levels does not suffice because of enterohepatic recirculation of MPA after formation of its main metabolite, a glucoronide termed MPA-G. However, abbreviated sampling schemes specific to mycophenolate mofetil (MMF) correlate well with the AUC for MPA. Cyclosporine interacts with MPA by inhibiting the multidrug resistance-associated protein 2 (MRP2). Higher MPA concentrations result in a decreased two h concentration of cyclosporine, while higher cyclosporine exposure results in a lower MPA exposure. There are no drug interactions between tacrolimus and MPA, and lower doses of MMF are required in combination with tacrolimus. Steroids may induce the clearance of MPA, which could account in part for the increasing MPA exposure following transplantation. TDM has allowed for dosing recommendations of MMF in children, which could lead to improved efficacy and minimization of toxicities. It is important that these provisional target levels are validated in prospective studies. The above points clearly indicate that there is a role for TDM of MPA in pediatric transplant recipients.

  1. Optimization of Deep Sedation with Spontaneous Respiration for Therapeutic Endoscopy Combining Propofol and Bispectral Index Monitoring

    Directory of Open Access Journals (Sweden)

    Kohei Matsumoto

    2015-01-01

    Full Text Available Background/Aims. This study aimed to establish optimal propofol anesthesia for therapeutic endoscopy, which has not been established. Methodology. We retrospectively investigated data on 89 patients who underwent upper-GI endoscopic submucosal dissection or endoscopic mucosal resection under anesthesia with propofol. Examined doses of propofol were changed according to efficacy and/or adverse events and classified into 5 periods. A bispectral index (BIS monitor was used at Period 5 to decrease the incidence of adverse events caused by oversedation. The initial dose of propofol was administered after bolus injection of pethidine hydrochloride (0.5 mg/kg, and 1.0 mL of propofol was added every minute until the patients fell asleep. Continuous and bolus infusion were performed to maintain sedation. When the patient moved or an adverse event occurred, the maintenance dose examined was increased or decreased by 5 mL/h regardless of body weight. Results. Dose combinations (introduction : maintenance and patient numbers for each period were as follows: Period 1 (n=27, 0.5 mg/kg : 5 mg/kg/h; Period 2 (n=11, 0.33 mg/kg : 3.3 mg/kg/h; Period 3 (n=7, 0.5 mg/kg : 3.3 mg/kg/h; Period 4 (n=14, 0.5 mg/kg : 2.5 mg/kg/h; Period 5 (n=30, 0.5 mg/kg : 2.5 mg/kg/h, using BIS monitor. During Period 5, an adverse event occurred in 10.0% of patients, which was lower than that for Periods 1–4. Conclusions. Period 5 propofol anesthesia with BIS protocol could be safe and useful for therapeutic endoscopy under deep sedation with spontaneous respiration.

  2. [Study on sociocultural history of therapeutic efficacy and processing of chinese materia medica].

    Science.gov (United States)

    Zheng, Jin-Sheng

    2006-10-01

    The historical evolving examples of the confirmation of therapeutic efficacy of some Chinese materia medica, the social fashion of using medicine, and the processing methods of Chinese materia medica indicate that the social trend of thoughts, customs and economic factors in different ages affected the various aspects of Chinese materia medica. So, Chinese materia medica possesses very outstanding social and cultural features. Not all the actions of Chinese materia medica recorded came from the experiences of doctors. The understanding level to the nature in different ages decides what kind of drugs they would accept. There are three kinds of drug processing in ancient times: effective medicinal processing, fantastic Taoist processing and invalid trading processing. Based on the study of sociocultural history of therapeutic efficacy and processing of Chinese materia medica. It is crucial that the history and medical literature research on Chinese materia medica and pharmacy should be raised to the position as important as clinical and experiment researches.

  3. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    single antigen such as HER2 in breast cancer is likely to be insufficient - instead we need a repertoire of multiple immunologically validated T cell...Award Number: W81XWH-11-1-0548 TITLE: Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer PRINCIPAL INVESTIGATOR...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection

  4. Depth-Sensor-Based Monitoring of Therapeutic Exercises

    Directory of Open Access Journals (Sweden)

    Mu-Chun Su

    2015-10-01

    Full Text Available In this paper, we propose a self-organizing feature map-based (SOM monitoring system which is able to evaluate whether the physiotherapeutic exercise performed by a patient matches the corresponding assigned exercise. It allows patients to be able to perform their physiotherapeutic exercises on their own, but their progress during exercises can be monitored. The performance of the proposed the SOM-based monitoring system is tested on a database consisting of 12 different types of physiotherapeutic exercises. An average 98.8% correct rate was achieved.

  5. Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms

    Institute of Scientific and Technical Information of China (English)

    Wei-Dong Du; Song-Bai Zheng; Zu-Rong Yuan; Jian Sun; Jian-Xiong Tang; Ai-Qun Cheng; Da-Ming Shen; Chun-Jin Huang; Xiao-Hua Song; Xiao-Feng Yu

    2003-01-01

    AIM: To observe the therapeutic efficacy of high-dose Vitamin C (Vit. C) on acute pancreatitis (AP), and to explore its potential mechanisms.METHODS: Eghty-four AP patients were divided into treatment group and control group, 40 healthy subjects were taken as a normal group. In the treatment group,Vit. C (10 g/day) was given intravenously for 5 days,whereas in the control group, Vit. C (1 g/day) was given intravenously for 5 days. Symptoms, physical signs, duration of hospitalization, complications and mortality rate were monitored. Meanwhile, serum amylase, urine amylase and leukocyte counts were also determined. The concentration of plasma vitamin C (P-VC), plasma lipid peroxide (P-LPO),plasma vitamin E (P-VE), plasma β-carotene (P-13-CAR),whole blood glutathione (WB-GSH) and the activity of erythrocyte surperoxide dimutase (E-SOD) and erythrocyte catalase (E-CAT) as well as T lymphocyte phenotype were measured by spectrophotometry in the normal group and before and after treatment with Vit. C in the treatment and the control group.RESULTS: Compared with the normal group, the average values of P-VC, P-VE, P-β-CAR, WB-GSH and the activity of E-SOD and E-CAT in AP patients were significantly decreased and the average value of P-LPO was significantly increased, especially in severe acute pancreatitis (SAP) patients (P<0.05. P-VC, P=0.045; P-VE, P=0.038; P=0.041;P-β-CAR, P=0.046; WB-GSH, P=0.039; E-SOD, P=0.019;E-CAT, P =0.020; P-LPO, P =0.038). Compared with the normal group, CD3 and CD4 positive cells in AP patients were significantly decreased. The ratio of CD4/CD8 and CD4 positive cells were decreased, especially in SAP patients (P<0.05. CD4/CD8, P =0.041; CD4, P =0.019). Fever and vomiting disappeared, and leukocyte counts and amylase in urine and blood become normal quicker in the treatment group than in the control group. Moreover, patients in treatment group also had a higher cure rate, a lower complication rate and a shorter in-ward days compared with

  6. Quantification of sunitinib and N-desethyl sunitinib in human EDTA plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry: validation and application in routine therapeutic drug monitoring

    NARCIS (Netherlands)

    Lankheet, N.; Steeghs, N.; Rosing, H.; Schellens, J.H.; Beijnen, J.H.; Huitema, A.D.

    2013-01-01

    BACKGROUND: Given the low therapeutic index, the large interindividual variability in systemic exposure and the positive exposure-efficacy relationship of sunitinib, there is a rationale for therapeutic drug monitoring (TDM) of sunitinib. To support TDM, a method for determination of sunitinib and

  7. Verantwoording en kosteneffectiviet van therapeutic drug monitoring (1) : Betere behandeling voor minder geld

    NARCIS (Netherlands)

    Touw, D.J.; Neef, C.; Vinks, A.A.

    2003-01-01

    There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review w

  8. Application of Fluorescent Protein Expressing Strains to Evaluation of Anti-Tuberculosis Therapeutic Efficacy In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Ying Kong

    Full Text Available The slow growth of Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, hinders development of new diagnostics, therapeutics and vaccines. Using non-invasive real-time imaging technologies to monitor the disease process in live animals would facilitate TB research in all areas. We developed fluorescent protein (FP expressing Mycobacterium bovis BCG strains for in vivo imaging, which can be used to track bacterial location, and to quantify bacterial load in live animals. We selected an optimal FP for in vivo imaging, by first cloning six FPs: tdTomato, mCherry, mPlum, mKate, Katushka and mKeima, into mycobacteria under either a mycobacterial Hsp60 or L5 promoter, and compared their fluorescent signals in vitro and in vivo. Fluorescence from each FP-expressing strain was measured with a multimode reader using the optimal excitation and emission wavelengths for the FP. After normalizing bacterial numbers with optical density, the strain expressing L5-tdTomato displayed the highest fluorescence. We used the tdTomato-labeled M. bovis BCG to obtain real-time images of pulmonary infections in living mice and rapidly determined the number of bacteria present. Further comparison between L5-tdTomato and Hsp60-tdTomato revealed that L5-tdTomato carried four-fold more tdTomato gene copies than Hsp60-tdTomato, which eventually led to higher protein expression of tdTomato. Evaluating anti-TB efficacy of rifampicin and isoniazid therapy in vitro and in vivo using the L5-tdTomato strain demonstrated that this strain can be used to identify anti-TB therapeutic efficacy as quickly as 24 h post-treatment. These M. bovis BCG reporter strains represent a valuable new tool for evaluation of therapeutics, vaccines and virulence.

  9. Factors Associated with Therapeutic Efficacy of Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Syndrome.

    Directory of Open Access Journals (Sweden)

    Sheng-Mou Hsiao

    Full Text Available To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB refractory to antimuscarinic therapy.All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox. The Global Response Assessment (GRA score ≥ 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed.Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR increased, and voiding efficiency (VE decreased after treatment. Female gender (odds ratio = 3.75 was the only independent factor associated with the success. Female gender (coefficient = 0.74, low baseline overactive bladder symptoms score (coefficient = -0.12 and the presence of OAB-wet (coefficient = 0.79 were independent factors associated with therapeutic efficacy (i.e., GRA score. VE (odds ratio = 0.062 was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%.The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection.ClinicalTrials.gov NCT01657409.

  10. Predictive markers of efficacy for an angiopoietin-2 targeting therapeutic in xenograft models.

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    Gallen Triana-Baltzer

    Full Text Available The clinical efficacy of anti-angiogenic therapies has been difficult to predict, and biomarkers that can predict responsiveness are sorely needed in this era of personalized medicine. CVX-060 is an angiopoietin-2 (Ang2 targeting therapeutic, consisting of two peptides that bind Ang2 with high affinity and specificity, covalently fused to a scaffold antibody. In order to optimize the use of this compound in the clinic the construction of a predictive model is described, based on the efficacy of CVX-060 in 13 cell line and 2 patient-derived xenograft models. Pretreatment size tumors from each of the models were profiled for the levels of 27 protein markers of angiogenesis, SNP haplotype in 5 angiogenesis genes, and somatic mutation status for 11 genes implicated in tumor growth and/or vascularization. CVX-060 efficacy was determined as tumor growth inhibition (TGI% at termination of each study. A predictive statistical model was constructed based on the correlation of these efficacy data with the marker profiles, and the model was subsequently tested by prospective analysis in 11 additional models. The results reveal a range of CVX-060 efficacy in xenograft models of diverse tissue types (0-64% TGI, median = 27% and define a subset of 3 proteins (Ang1, EGF, Emmprin, the levels of which may be predictive of TGI by Ang2 blockade. The direction of the associations is such that better efficacy correlates with high levels of target and low levels of compensatory/antagonizing molecules. This effort has revealed a set of candidate predictive markers for CVX-060 efficacy that will be further evaluated in ongoing clinical trials.

  11. Systematic Review of Biomarkers To Monitor Therapeutic Response in Leishmaniasis

    NARCIS (Netherlands)

    Kip, Anke E; Balasegaram, Manica; Beijnen, Jos H; Schellens, Jan H M; de Vries, Peter J; Dorlo, Thomas P C

    2015-01-01

    Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particu

  12. Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

    Directory of Open Access Journals (Sweden)

    Xie S

    2011-10-01

    Full Text Available Shuyu Xie1,*, Baoliang Pan1,*, Baoxin Shi2, Zhuangzhi Zhang2, Xu Zhang2, Ming Wang1, Wenzhong Zhou11Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2Veterinary Research Institute, Xinjiang Academy of Animal Science, Xinjiang, People’s Republic of China *These authors contributed equally to this study Abstract: Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and -11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91

  13. Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional Imaging Predictors of Therapeutic Failure.

    Science.gov (United States)

    Campos, Cécile; Perrey, Antoine; Lambert, Céline; Pereira, Bruno; Goutte, Marion; Dubois, Anne; Goutorbe, Felix; Dapoigny, Michel; Bommelaer, Gilles; Hordonneau, Constance; Buisson, Anthony

    2017-06-01

    Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). Among 84 patients, therapeutic failure rate within 60 months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37-11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p = 0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p = 0.047) were associated with short-term clinical failure. Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.

  14. Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

    Science.gov (United States)

    Dolton, Michael J; Ray, John E; Marriott, Deborah; McLachlan, Andrew J

    2012-06-01

    Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for other triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. This review examines the available evidence for a relationship between plasma concentration and clinical efficacy for posaconazole, as well as evaluating the utility of TDM and providing provisional target concentrations for posaconazole therapy. Increasing evidence supports an exposure-response relationship for plasma posaconazole concentrations for prophylaxis and treatment of IFIs; a clear relationship has not been identified between posaconazole concentration and toxicity. Intracellular and intrapulmonary concentrations have been studied for posaconazole but have not been correlated to clinical outcomes. In view of the high mortality and cost associated with the treatment of IFIs, increasing evidence of an exposure-response relationship for posaconazole efficacy in the prevention and treatment of IFIs, and the common finding of low posaconazole concentrations in patients, TDM for posaconazole is likely to be of significant clinical utility. In patients with subtherapeutic posaconazole concentrations, increased dose frequency, administration with high-fat meals, and withdrawal of interacting medications from therapy are useful strategies to improve systemic absorption.

  15. Review of therapeutic drug monitoring of anticancer drugs part two--targeted therapies.

    Science.gov (United States)

    Widmer, Nicolas; Bardin, Christophe; Chatelut, Etienne; Paci, Angelo; Beijnen, Jos; Levêque, Dominique; Veal, Gareth; Astier, Alain

    2014-08-01

    Most of oral targeted therapies are tyrosine kinase inhibitors (TKIs). Oral administration generates a complex step in the pharmacokinetics (PK) of these drugs. Inter-individual PK variability is often large and variability observed in response is influenced not only by the genetic heterogeneity of drug targets, but also by the pharmacogenetic background of the patient (e.g. cytochome P450 and ABC transporter polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug-drug interactions). Retrospective studies have shown that targeted drug exposure, reflected in the area under the plasma concentration-time curve (AUC) correlates with treatment response (efficacy/toxicity) in various cancers. Nevertheless levels of evidence for therapeutic drug monitoring (TDM) are however heterogeneous among these agents and TDM is still uncommon for the majority of them. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug-drug interactions and/or concerns over adherence treatment. Interpatient PK variability observed with monoclonal antibodies (mAbs) is comparable or slightly lower to that observed with TKIs. There are still few data with these agents in favour of TDM approaches, even if data showed encouraging results with rituximab, cetuximab and bevacizumab. At this time, TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Use of saliva in therapeutic drug monitoring of caffeine in preterm infants

    NARCIS (Netherlands)

    de Wildt, SN; Kerkvliet, KTM; Wezenberg, MGA; Ottink, S; Hop, WCJ; Vulto, AG; van den Anker, JN

    2001-01-01

    Caffeine is frequently used to treat apnea of prematurity in preterm infants. Because caffeine has a narrow therapeutic window, plasma concentrations are generally monitored weekly. It would be advantageous to monitor this therapy without blood sampling; saliva might offer this possibility. Paired p

  17. Use of saliva in therapeutic drug monitoring of caffeine in preterm infants

    NARCIS (Netherlands)

    de Wildt, SN; Kerkvliet, KTM; Wezenberg, MGA; Ottink, S; Hop, WCJ; Vulto, AG; van den Anker, JN

    2001-01-01

    Caffeine is frequently used to treat apnea of prematurity in preterm infants. Because caffeine has a narrow therapeutic window, plasma concentrations are generally monitored weekly. It would be advantageous to monitor this therapy without blood sampling; saliva might offer this possibility. Paired p

  18. Neuromyelitis optica: Contribution of therapeutic responses markers monitoring in patients given rituximab.

    Science.gov (United States)

    Romero, G; Ticchioni, M; Cohen, M; Rosenthal-Allieri, M A; Mondot, L; Lebrun Frenay, C

    2016-03-01

    Neuromyelitis optica (NMO) is a central nervous system inflammatory autoimmune disease characterized by medullary and/or optical nerve damage. It is rare but life-threatening. Concerning the treatment of NMO, many drugs have been used in background therapy. Some studies have shown efficacy of rituximab (an antiCD20 monoclonal anti-body) either on the reduction of the annual number of exacerbation or the mean score EDSS. In 2013, a Korean team reported a new protocol during which they administered rituximab only when memory B lymphocytes CD27+ were detectable in the bloodstream. In our patient, institution of this protocol led to clinical benefit with a major decrease in the EDSS score over time (7 in August 2012 vs. 1 in October 2015), a reduction of the total administered dose (4g in 2013 vs. 1.375g in 2014 vs. 0g in 2015) and side effects. Compared with the rate of theoretical administration, health expenditure savings reached 1700 Euros per month over the 11-month treatment. Monitoring therapeutic response markers with memory B lymphocyte counts appear to be an efficient cost-effective way to measure clinical efficiency, reduce total doses, and limit side effects.

  19. Engineering novel targeted nanoparticle formulations to increase the therapeutic efficacy of conventional chemotherapeutics against multiple myeloma

    Science.gov (United States)

    Ashley, Jonathan D.

    inhibition in vivo. Carfilzomib, another proteasome inhibitor, was embedded into the lipid bilayer of liposomes to improve its therapeutic efficacy. VLA-4 antagonist peptides were also incorporated to facilitate MM cell targeting and uptake. The liposomal carfilzomib nanoparticles demonstrated improved therapeutic index and synergy with doxorubicin compared to free carfilzomib. These nanoparticle formulations can significantly improve the efficacy of the respective therapeutic agents and have an immense potential to positively impact the treatment of MM providing for improved patient outcomes.

  20. UV therapy: Physiotherapists' perception of therapeutic efficacy and barriers to usage

    Directory of Open Access Journals (Sweden)

    Jibril Mohammed Nuhu, MSc

    2014-06-01

    Full Text Available This study was conducted to assess the perception of efficacy of ultraviolet (UV light therapy and barriers to its use among physiotherapists. A purpose-designed questionnaire containing 29 items, seeking information on perception of efficacy of UV therapy and perceived barriers to its use, was administered to physiotherapists in Northwestern Nigeria. With a response rate of 97%, it was demonstrated that almost 70% of the respondents perceived UV therapy to be effective and only 59.3% of them had ever used UV therapy for treatment purposes. In general, the major barrier to the use of the modality was nonavailability of UV therapy machine (66.1% followed by availability of a substitute treatment modality (13.5%. Lack of referral of patients with indications for possible use of UV therapy accounted for 10.2%. The study also found significant association between the use of UV therapy by the respondents and the perception of its therapeutic efficacy (p < 0.05, and perception of the modality as being abandoned by physiotherapists (p < 0.05. It was concluded that despite the low level of use of UV therapy mainly due to its unavailability, physiotherapists in Northwestern Nigeria perceived the modality as being efficacious.

  1. Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Brandes Ralf P

    2011-06-01

    Full Text Available Abstract Background Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension.

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

    Directory of Open Access Journals (Sweden)

    Sunee Lertsinudom

    2014-12-01

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

  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.

  4. Improved Therapeutic Efficacy in Bone and Joint Disorders by Targeted Drug Delivery to Bone.

    Science.gov (United States)

    Takahashi, Tatsuo

    2016-01-01

     Site-specific drug delivery to bone is considered achievable using acidic amino acid (L-Asp or L-Glu) homopeptides known as acidic oligopeptides. We found that fluorescence-labeled acidic oligopeptides containing six or more residues bound strongly to hydroxyapatite, which is a major component of bone, and were selectively delivered to and retained in bone after systemic administration. We explored the applicability of this result for drug delivery by conjugation of estradiol and levofloxacin with an L-Asp hexapeptide. We also similarly tagged enzymes (tissue-nonspecific alkaline phosphatase, β-glucuronidase, and N-acetylgalactosamine-6-sulfate sulfatase) and decoy receptors (endogenous secretory receptor for advanced glycation end products and etanercept) to assess whether these would improve therapeutic efficacy. The L-Asp hexapeptide-tagged drugs, including enzymes and decoy receptors, were efficiently delivered to bone in comparison with the untagged drugs. An in vivo experiment confirmed the efficacy of L-Asp hexapeptide-tagged drugs on bone and joint disorders, although there was some loss of bioactivity of estradiol and levofloxacin in vitro, suggesting that the acidic hexapeptide was partly removed by hydrolysis in the body after delivery to bone. It was expected that the ester linkage to the hexapeptide would be susceptible to hydrolysis in situ, releasing the drug from the acidic oligopeptide. These results support the usefulness of acidic oligopeptides as bone-targeting carriers for therapeutic agents. We present some pharmacokinetic and pharmacological properties of the L-Asp hexapeptide-tagged drugs.

  5. Dried blood spot analysis for therapeutic drug monitoring of pazopanib.

    Science.gov (United States)

    de Wit, Djoeke; den Hartigh, Jan; Gelderblom, Hans; Qian, Yanwen; den Hollander, Margret; Verheul, Henk; Guchelaar, Henk-Jan; van Erp, Nielka P

    2015-12-01

    Dried blood spot (DBS) sampling is potentially a more patient-friendly and flexible alternative to venous sampling of pazopanib. This study determined the agreement between pazopanib DBS and plasma concentrations to facilitate implementation of pazopanib DBS sampling into clinical practice. Paired DBS and plasma samples were collected in 12 patients. Pazopanib plasma concentrations were calculated from DBS concentrations using the formula: plasma concentration = DBSconcentration /(1 - hematocrit). Passing-Bablok and Bland-Altman analyses were used to determine the agreement between calculated and measured plasma concentrations. We predefined a clinical acceptance limit of 25% for the Bland-Altman analysis. Passing-Bablok analysis showed a small constant (intercept estimate, -8.53 [95%CI, -12.22 to -4.41]) and slightly proportional (slope estimate, 1.15 [95%CI, 1.04-1.24]) bias between calculated and measured concentrations. This bias was clinically nonrelevant, as shown by Bland-Altman analysis; the mean ratio of calculated to measured concentrations was 0.94 (95%CI, 0.65-1.23). The clinical acceptance limits were well within these 95% limits of agreement. More specifically, 92.6% of the data points were within the predefined acceptance limits. Pazopanib plasma concentrations can be accurately calculated from DBS concentrations. Although validation of DBS cards prepared by patients themselves is required, these results show that DBS sampling can be used to monitor pazopanib therapy in clinical practice.

  6. [Vasomotor tone and CBP : monitoring components, pratical and therapeutic approaches].

    Science.gov (United States)

    Isetta, C; Janot, N

    2012-05-01

    The vasomotor tone is an essential determinant of blood pressure. Vascular resistance is the result of a calculation including vasomotor tone, blood flow and blood viscosity. The vascular tone is modulated by the sympathetic system and the direct actions of drugs (patient's pathology, anaesthesia). The pressure and flow allow the vascular tone apprehension. A decrease in vasomotor tone lowers the mean arterial pressure and may cause an intense vasoplegia with arterial vascular resistance below than 800 dyn/s/cm(5) leading to a lack of tissue oxygenation. Vasomotor paralysis can be caused by the patient medications or an intense inflammatory reaction starting at the extracorporeal circulation onset. Monitoring parameters of extracorporeal circulation such as pressure, flow, arterial and venous oxygen saturation, blood level in the venous reservoir, and extensively blood gases, haemoglobin, CO(2) partial pressure level of the oxygenator vent, bispectral index, and oxygen saturation of cerebral tissue are reviewed. They will know the vasoplegia consequences and bear an indication of adequate tissue oxygenation. It may be obtained by using vasopressors (ephedrine, norepinephrine, terbutalin and vasopressin) methylene blue, increasing blood viscosity (erythrocytes) and blood flow, even by inducing hypothermia.

  7. Therapeutic efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in a high-transmission area in northwest Ethiopia.

    Science.gov (United States)

    Teklemariam, Michael; Assefa, Ashenafi; Kassa, Moges; Mohammed, Hussien; Mamo, Hassen

    2017-01-01

    Malaria, particularly due to Plasmodium falciparum, remains a major public health threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line antimalarial drug against uncomplicated P. falciparum malaria in the country since 2004. Regular monitoring of antimalarial drugs is recommended by the World Health Organization (WHO) to help early detection of drug resistant strains of the parasite and contain their rapid spread. The objective of this study was to assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia. The study site was Setit Humera, northwest Ethiopia. Single-arm prospective study of a 28-day follow-up was conducted from October 2014 to January 2015 according to the revised WHO 2009 drug efficacy study protocol. Study end-points were classified into primary end-point and secondary end-point. While the primary end-point was the day-28 adequate clinical and parasitological response the secondary end-points were clinical and parasitological evaluations (parasite, fever and gametocyte clearance rate, incidence of drug adverse events) and the relative increment in hemoglobin (Hb) level from baseline to day (D) 14 and D28. A total of 92 patients were enrolled and 79 had completed the 28-day follow-up period. The overall cure rate was 98.8% with 95% confidence interval of 0.915-0.998 without polymerase chain reaction correction. The parasite clearance rate was high with fast resolution of clinical symptoms; 100% of the study participants cleared parasitaemia and fever on D3. Gametocyte carriage was reduced from 7% on D0 to 1% on D3 and complete clearance was achieved on D14. Mean Hb concentration significantly increased on D28 compared to that on D14. There was no serious adverse event. AL was efficacious and safe in a high-transmission setting for treatment of uncomplicated falciparum malaria.

  8. What is the efficacy of physical therapeutics for treating neuropathic pain in spinal cord injury patients?

    Science.gov (United States)

    Fattal, C; Kong-A-Siou, D; Gilbert, C; Ventura, M; Albert, T

    2009-03-01

    Evaluate the place and level of proof of physical therapeutics for treating neuropathic pain in spinal cord injury (SCI) patients. Literature review from three databases: PubMed, Embase, Pascal. The following keywords were selected: chronic neuropathic pain/non-pharmacological treatment; transcutaneous electrical nerve stimulation, physiotherapy, acupuncture, physical therapy, transcranial magnetic stimulation, heat therapy, ice therapy, cold therapy, massage, ultrasound, alternative treatment, complementary treatment, occupational therapy. The articles were analyzed using the double-reading mode. Three techniques emerge from the literature: magnetic or electrical transcranial stimulation, transcutaneous electrical nerve stimulation and acupuncture. Even though the first method is not easily accessible on a daily basis it is the one that yields the most promising results validated by Grade B studies. Healthcare professionals remain faithful to pain-relieving transcutaneous neurostimulation for both segmental neuropathic pain and below-level central neuropathic pain. Acupuncture is advocated by Canadian teams and could offer some interesting options; however, to this day, it does not have the methodological support and framework required to validate its efficacy. All other physical therapies are used in a random way. Only below-level massages are advocated by the patients themselves. To this day, no study can validate the integration of physical therapy as part of the array of therapeutics used for treating neuropathic pain in SCI patients. In the future, it will require controlled and randomized therapeutic studies on homogenous groups of SCI patients, to control the various confusion factors.

  9. Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ning, Shoucheng [Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305 (United States); Bednarski, Mark [Department of Radiology, Stanford University Medical Center, Stanford, CA 94305 (United States); Oronsky, Bryan; Scicinski, Jan [RadioRx, Inc., Mountain View, CA 94040 (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305 (United States)

    2014-05-09

    Highlights: • Glycidyl nitrate (GLYN) is a NO generating small molecule and has ability to release NO on bioactivation in tumor cells. • GLYN-induced intracellular NO generation was attenuated by NO scavengers. • GLYN increases tumor blood flow in tumor-bearing animal model. • GLYN significantly increased the anti-tumor efficacy of cisplatin and radiation therapy in mice. • GLYN is well tolerated with no obvious systemic toxicities at its effective therapeutic doses in preclinical animal studies. - Abstract: Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds.

  10. Short report: therapeutic efficacy of chloroquine combined with primaquine against Plasmodium falciparum in northeastern Papua, Indonesia.

    Science.gov (United States)

    Baird, J Kevin; Wiady, Iwa; Sutanihardja, Awalludin; Suradi; Purnomo; Basri, Hasan; Sekartuti; Ayomi, Ester; Fryauff, David J; Hoffman, Stephen L

    2002-06-01

    Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1-1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1-1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% Cl, 0.04-2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum.

  11. Therapeutic drug monitoring (TDM of atazanavir in pregnancy

    Directory of Open Access Journals (Sweden)

    S Khoo

    2012-11-01

    for ATV in pregnancy. Lower [ATV] were seen in T2 and T3 when compared to T1. However, such findings were not associated with viral breakthrough or HIV transmissions. Nonetheless, careful monitoring of women in pregnancy is required, and if there is concern for inadequate levels, dose adjustment of ATV upward from 300 mg to 400 mg may be an option.

  12. Hand hygiene monitoring technology: a systematic review of efficacy.

    Science.gov (United States)

    Srigley, J A; Gardam, M; Fernie, G; Lightfoot, D; Lebovic, G; Muller, M P

    2015-01-01

    Electronic and video monitoring systems (EMS/VMS) may improve hand hygiene by providing feedback, real-time reminders or via the Hawthorne effect. The aim of this systematic review was to assess the efficacy of EMS/VMS in improving hand hygiene or reducing the incidence of healthcare-associated infection (HCAI). Experimental and quasi-experimental studies were included if they measured any hand hygiene outcome and/or HCAI incidence. Of the studies included, seven used system-defined compliance (SDC) (N = 6) or hand hygiene event rate (N = 1) as their outcome. SDC differed for all systems. Most (N = 6) were single ward studies. Two uncontrolled pretest‒post-test studies evaluating EMS that provided voice prompts showed increases in SDC, but risk of bias was high. Two uncontrolled time-series analyses of VMS that provided aggregate feedback demonstrated large, sustained improvement in SDC and were at moderate risk of bias. One non-randomized controlled trial of EMS with aggregate feedback found no difference in hand hygiene frequency but was at high risk of bias. Two studies evaluated EMS providing individual feedback and real-time reminders. A pretest‒post-test study at high risk of bias showed an increase in SDC. An RCT at low risk of bias showed 6.8% higher SDC in the intervention arm partially due to a fall in SDC in the control arm. In conclusion, the overall study quality was poor. The study at lowest risk of bias showed only a small increase in SDC. VMS studies at moderate risk of bias showed rapid and sustained increases in SDC. Data were insufficient to recommend EMS/VMS. Future studies should prioritize testing of VMS using stronger study designs including control arms and validated, system-independent measures of hand hygiene. Copyright © 2014 Taibah University. Published by Elsevier Ltd. All rights reserved.

  13. A multifunctional drug combination shows highly potent therapeutic efficacy against human cancer xenografts in athymic mice.

    Directory of Open Access Journals (Sweden)

    Xiu-Jun Liu

    Full Text Available The tumor microenvironment plays a crucial role during tumor development. Integrated combination of drugs that target tumor microenvironment is a promising approach to anticancer therapy. Here, we report a multifunctional combination of low-cytotoxic drugs composed of dipyridamole, bestatin and dexamethasone (DBDx which mainly acts on the tumor microenvironment shows highly potent antitumor efficacy in vivo. In mouse hepatoma H22 model, the triple drug combination showed synergistic and highly potent antitumor efficacy. The combination indices of various combinations of the triple drugs were between 0.2 and 0.5. DBDx inhibited the growth of a panel of human tumor xenografts and showed no obvious systemic toxicity. At tolerated doses, DBDx suppressed the growth of human hepatocellular carcinoma BEL-7402, HepG2, and lung adenocarcinoma A549 xenografts by 94.5%, 93.7% and 96.9%, respectively. Clonogenic assay demonstrated that DBDx showed weak cytotoxicity. Western blot showed that Flk1 and Nos3 were down-regulated in the DBDx-treated group. Proteomic analysis showed that DBDx mainly affected the metabolic process and immune system process; in addition, the angiogenesis and VEGF signaling pathway were also affected. Conclusively, DBDx, a multifunctional drug combination of three low-cytotoxic drugs, shows synergistic and highly potent antitumor efficacy evidently mediated by the modulation of tumor microenvironment. Based on its low-cytotoxic attributes and its broad-spectrum antitumor therapeutic efficacy, this multifunctional combination might be useful in the treatment of cancers, especially those refractory to conventional chemotherapeutics.

  14. Therapeutic efficacy of differentiated versus undifferentiated mesenchymal stem cells in experimental type I diabetes in rat

    Directory of Open Access Journals (Sweden)

    M.A. Wassef

    2016-03-01

    Full Text Available Selective MSCs differentiation protocol into pancreatic beta cells was conducted in the present study using exendin-4 and TGF-beta. Differentiated and undifferentiated MSCs were assessed in experimental type I diabetes in rats. Ninety female white albino rats were included in the study and divided equally (n=15/group into 6 groups: healthy control, healthy control rats received acellular tissue culture medium, diabetic rats, diabetic rats received acellular tissue culture medium, diabetic rats received undifferentiated MSCs and diabetic rats received differentiated MSCs. Therapeutic efficacy of undifferentiated versus differentiated MSCs was evaluated via assessment of quantitative gene expressions of insulin1, insulin 2, Smad-2, Smad-3, PDX-1, PAX-4, neuroD. Blood glucose and insulin hormone levels were also assessed. Results showed that quantitative gene expressions of all studied genes showed significant decrease in diabetic rat groups. Use of undifferentiated and differentiated MSCs led to a significant elevation of expression levels of all genes with more superior effect with differentiated MSCs except smad-2 gene. As regards insulin hormone levels, use of either undifferentiated or differentiated MSCs led to a significant elevation of its levels with more therapeutic effect with differentiated MSCs. Blood glucose levels were significantly decreased with both undifferentiated and differentiated MSCs in comparison to diabetic groups but its levels were normalized 2 months after injection of differentiated MSCs. In conclusion, use of undifferentiated or differentiated MSCs exhibited significant therapeutic potentials in experimental type I diabetes in rats with more significant therapeutic effect with the use of differentiated MSCs.

  15. Computerized clinical decision support systems for therapeutic drug monitoring and dosing: A decision-maker-researcher partnership systematic review

    Directory of Open Access Journals (Sweden)

    Weise-Kelly Lorraine

    2011-08-01

    Full Text Available Abstract Background Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety. Computerized clinical decision support systems (CCDSSs may improve the net benefit of these drugs. The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing. Methods We conducted a decision-maker-researcher partnership systematic review. Studies from our previous review were included, and new studies were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Inspec databases. Randomized controlled trials assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. A study was considered to have a positive effect (i.e., CCDSS showed improvement if at least 50% of the relevant study outcomes were statistically significantly positive. Results Thirty-three randomized controlled trials were identified, assessing the effect of a CCDSS on management of vitamin K antagonists (14, insulin (6, theophylline/aminophylline (4, aminoglycosides (3, digoxin (2, lidocaine (1, or as part of a multifaceted approach (3. Cluster randomization was rarely used (18% and CCDSSs were usually stand-alone systems (76% primarily used by physicians (85%. Overall, 18 of 30 studies (60% showed an improvement in the process of care and 4 of 19 (21% an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycaemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range. Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing, specifically insulin and vitamin K antagonist dosing. However, studies were small and generally of modest quality, and effects on patient outcomes were uncertain, with no convincing

  16. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  17. Eudragit EPO nanoparticles: application in improving therapeutic efficacy and reducing ulcerogenicity of meloxicam on oral administration.

    Science.gov (United States)

    Khachane, Parag; Date, Abhijit A; Nagarsenker, Mangal S

    2011-08-01

    The objective of this investigation was to evaluate the potential of Eudragit EPO nanoparticles (EPO NP) in improving therapeutic efficacy of meloxicam (MLX). MLX loaded EPO NP were prepared by nanoprecipitation method and were characterized for particle size, encapsulation efficiency and for morphology. The in vitro dissolution profile of MLX loaded EPO NP and MLX suspension was evaluated. MLX loaded EPO NP had particle size of approximately 100 nm and the encapsulation efficiency of MLX was approximately 90%. The EPO NP significantly improved anti-inflammatory activity of MLX (P EPO NP Oral administration of MLX loaded EPO NP also resulted in lesser ulcerogenicity as compared to that of MLX suspension indicating that nanoparticles can also decrease the adverse effects associated with MLX treatment.

  18. Evaluation of the efficacy of a therapeutic HIV vaccine by in vitro stimulation assay.

    Science.gov (United States)

    He, Xiaozhou; Wang, Wandi; Xu, Ke; Feng, Xia; Zeng, Yi

    2017-03-01

    A novel method for HIV vaccine efficacy evaluation was established and the experimental conditions optimized. This novel method was then applied to determine whether a recombinant adenovirus type 5 HIV therapeutic vaccine expressing Gag antigen (Ad5-HIVgag) could stimulate HIV-specific cellular responses in vitro. The results indicated that HIV-specific IFN-gama production lymphocytes were induced by the Ad5-HIVgag vaccine. Compared with other methods, this in vitro stimulation method is safe and time-efficient, and the result is more intuitive. It has the potential to be regarded as a supplement to other methods for evaluating the IFN-gamma production by PBMCs to HIV vaccination. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Variability in the pharmacokinetics of mycophenolic acid: Implications for therapeutic drug monitoring

    NARCIS (Netherlands)

    B.C.M. de Winter (Brenda)

    2010-01-01

    textabstractMycophenolate mofetil (MMF) is an immunosuppressive drug used to prevent rejection following solid organ transplantation. MMF was introduced in 1995 with a recommended fixed-dose regimen of 1 g twice daily. Nowadays, dose individualization using therapeutic drug monitoring (TDM) of the a

  20. The role of therapeutic drug monitoring in pediatric HIV/AIDS.

    NARCIS (Netherlands)

    Burger, D.M.

    2010-01-01

    International guidelines do not recommend therapeutic drug monitoring (TDM) of HIV-infected children as a routine measurement as part of medical management. There are, however, several clinical scenarios in which TDM may be indicated. Underdosing may be one of the major risks, especially in younger

  1. Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting Concentration

    OpenAIRE

    Dolton, Michael J; Ray, John E.; Chen, Sharon C.-A.; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-01-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaco...

  2. Posaconazole Exposure-Response Relationship: Evaluating the Utility of Therapeutic Drug Monitoring

    OpenAIRE

    Dolton, Michael J; Ray, John E.; Marriott, Deborah; McLachlan, Andrew J

    2012-01-01

    Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely ...

  3. Therapeutic drug monitoring: an aid to optimising response to antiretroviral drugs?

    NARCIS (Netherlands)

    Aarnoutse, R.E.; Schapiro, J.M.; Boucher, C.A.B.; Hekster, Y.A.; Burger, D.M.

    2003-01-01

    Therapeutic drug monitoring (TDM) has been proposed as a means to optimise response to highly active antiretroviral therapy (HAART) in HIV infection. Protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine satisfy many criteria for TDM. Nuc

  4. Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

    NARCIS (Netherlands)

    Zuur, Marlanka A.; Bolhuis, Mathieu S.; Anthony, Richard; den Hertog, Alice; van der Laan, Tridia; Wilffert, Bob; Lange, de Wiel; van Soolingen, Dick; Alffenaar, Jan-Willem C.

    Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order

  5. Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA.

    Science.gov (United States)

    Chinen, Yasutsugu; Higa, Takeshi; Tomatsu, Shunji; Suzuki, Yasuyuki; Orii, Tadao; Hyakuna, Nobuyuki

    Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipient's lymphocytes reached almost half of normal level within two years after BMT. For the successive 9+ years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donor's, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA.

  6. Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Enfranze, north-west Ethiopia.

    Science.gov (United States)

    Getnet, Gebeyaw; Fola, Abebe Alemu; Alemu, Agersew; Getie, Sisay; Fuehrer, Hans-Peter; Noedl, Harald

    2015-06-24

    Plasmodium falciparum accounts for approximately 60% of malaria cases in Ethiopia and artemether-lumefantrine has been used as a first-line treatment for uncomplicated P. falciparum malaria since 2004. The aim of this study was to assess the therapeutic efficacy of artemether-lumefantrine (AL) for the treatment of uncomplicated P. falciparum malaria in north-western Ethiopia. A 28-day one-arm, prospective evaluation of the clinical and parasitological response to the first-line treatment for uncomplicated P. falciparum malaria was conducted in Enfranze Health Centre in accordance with the 2009 WHO efficacy study guidelines. Patients were treated with a 3-day course of AL and clinical and parasitological parameters were monitored over a 28-day follow-up. All data from recruited patients were imported into an electronic data base and Kaplan-Meier survival analysis was used for analysing primary [early treatment failures (ETF), late clinical failure (LCF), late parasitological failures (LPF), and adequate clinical and parasitological response (ACPR)] and secondary (PCT, GCT and FCT) outcomes. Eighty patients were enrolled and all of them completed the 28-day follow-up period. The PCR-corrected cure rate was 95.0% (95% CI 87.0-98.4%) and there were two ETF, one LCF and three LPF. Two of the LPF were classified as re infections by PCR. Seventy three point seven five percent, 91.25 and 95% of patients had cleared their parasitaemia by days 1, 2, and 3, respectively, and 75, 91.25 and 96.25% of patients had cleared their fever by days 1, 2, and 3. All patients completely cleared their gametocytes by day 7. The relatively high cure rate, low proportion of patients still positive on day 3 as well as parasite clearance times in this study would indicate no imminent threat of artemisinin resistance development in the region. However, the threat of spreading or de novo development of artemisinin resistance warrants regular monitoring of drug efficacy throughout the region.

  7. The development of new oximes and the evaluation of their reactivating, therapeutic and neuroprotective efficacy against tabun.

    Science.gov (United States)

    Kassa, Jiri; Kuca, Kamil; Karasova, Jana; Musilek, Kamil

    2008-10-01

    Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. The antidotal treatment of tabun acute poisonings still represents a serious problem and the development of new, more effective AChE reactivators to achieve the satisfactorily effective antidotal treatment of acute poisonings with tabun still represents very important goal. Since 2003, we have prepared around 200 new AChE reactivators. Their potency to reactivate tabun-inhibited acetylcholinesterase has been subsequently evaluated using our in vitro screening test. Afterwards, promising compounds were selected and kinetic parameters and reactivation constants were determined. Then, the best reactivators were subjected to the in vivo studies (toxicity test, the evaluation of therapeutic, reactivating and neuroprotective efficacy) and their potency to counteract the acute toxicity of tabun is compared to the therapeutic, reactivating and neuroprotective efficacy of commonly used oximes - obidoxime and the oxime HI-6. According to the results obtained, the newly synthesized oxime K075 showed the highest potency to reduce tabun-induced acute lethal toxicity while the therapeutic potency of obidoxime and the oxime HI-6 was significantly lower. The therapeutic efficacy of oximes studied corresponds to their reactivating efficacy in vivo as well as in vitro. The potency of all newly synthesized oximes to reactivate tabun-inhibited AChE is comparable with obidoxime with the exception of K074 that is significantly more efficacious in the brain. In addition, all newly synthesized oximes combined with atropine seem to be effective antidotes for a decrease in tabun-induced acute neurotoxicity. While the neuroprotective efficacy of obidoxime in combination with atropine is similar to the potency of newly synthesized oximes, the ability of the oxime HI-6 combined with atropine to counteract tabun

  8. Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma.

    Science.gov (United States)

    Dai, Wei; Gao, Quangen; Qiu, Jianping; Yuan, Jianmao; Wu, Guoliang; Shen, Genhai

    2016-05-01

    Quercetin (Q), a flavonoid compound, which is obtained in variety of fruits, seeds, and vegetables, has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of Q in human hepatocellular carcinoma (HCC) are still limited. The present study is conducted to investigate the anticancer efficacy and adjuvant chemotherapy action of Q in HCC. HCC cell lines HepG2 and SMCC-7721 were treated with different concentrations of Q. The antiproliferative effects of Q were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the apoptosis and cell cycle dynamics were assessed by flow cytometry; the expression of apoptosis-associated proteins were evaluated by Western blot and immunohistochemistry staining; the tumor growth in vivo was evaluated in a xenograft mouse model. Our results showed that Q effectively inhibited human HCC cell proliferation and induced apoptosis by upregulating the expression of Bad and Bax and downregulating the expression of Bcl-2 and Survivin in vitro. Furthermore, Q obviously inhibited the tumor growth and enhanced the 5-fluorouracil (5-FU) therapeutic efficacy in vitro and in vivo. Taken together, our findings highlight that Q effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating Q is a potential treatment option for HCC.

  9. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  10. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

    Science.gov (United States)

    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho

    2016-01-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

  11. Therapeutic efficacy of natural prostaglandin in the treatment of pyometra in bitches

    Directory of Open Access Journals (Sweden)

    Basanti Jena

    2013-12-01

    Full Text Available Aim: The current study was done to study the therapeutic effect of natural prostaglandin in treatment of canine pyometra. Materials and Methods: Seven bitches were treated with natural PGF2 á i.e. dinoprost tromethamine at the dose rate of 100 μg/kg body weight subcutaneously once daily for 7 days with supportive therapies. The physiological, haematological and biochemical parameters were studied before (0th day and after treatment (8th day. Therapeutic efficacy was assessed in terms of return of abnormal parameters to either normal or near normal value as compared to the untreated control group, intensity of side effects and post treatment reproductive status. Results: All physiological, haematological and biochemical parameters in the seven treated bitches returned to normal range at the end of treatment. The intensity of side effects was quite severe in the treatment group. Six bitches came to estrus within 2 months of treatment and out of them four conceived on subsequent mating. In rest three bitches there was recurrence of pyometra within 4 months of treatment. Conclusion: Though conception rate of recovered bitches is decreased when compared with that of normal healthy bitches still this treatment protocol can be used successfully in treatment of canine pyometra to conserve the breeding capability of bitches. [Vet World 2013; 6(6.000: 295-299

  12. Therapeutic efficacy of rose oil: A comprehensive review of clinical evidence

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    Safieh Mohebitabar

    2017-04-01

    Full Text Available Objective: Rose oil is obtained from the petals of difference Rosa species especially Rosa centifolia L. and Rosa damascena Mill. Various pharmacological properties have been attributed to rose oil. The aim of the present study was to review the rose oil therapeutic effects which had been clinically evaluated in trial studies. Materials and Methods: Google scholar, PubMed, Cochrane Library, and Scopus were searched for human studies which have evaluated the therapeutic effects of rose oil and published in English language until August 2015. Results: Thirteen clinical trials (772 participants were included in this review. Rose oil was administered via inhalation or used topically. Most of the studies (five trials evaluated the analgesic effect of rose oil. Five studies evaluated the physiological relaxation effect of rose oil. Anti-depressant, psychological relaxation, improving sexual dysfunction, and anti-anxiety effects were the other clinical properties reported for rose oil. Conclusion: Numerous studies on the pharmacological properties of rose oil have been done in animals, but studies in humans are few.  In this study, it was observed that rose oil had physiological and psychological relaxation, analgesic and anti-anxiety effects. To obtain conclusive results on the efficacy and safety of rose oil, further clinical trials with larger sample size and better designation are required.

  13. Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer.

    Science.gov (United States)

    Igarashi, Akira; Konno, Hiroyuki; Tanaka, Tatsuo; Nakamura, Satoshi; Sadzuka, Yasuyuki; Hirano, Toru; Fujise, Yutaka

    2003-11-30

    Photodynamic therapy (PDT) has been established as a potent and less invasive treatment for gastrointestinal tumors. The aim of the present study was to investigate whether or not liposomalization of the photosensitizer enhanced the therapeutic efficacy of PDT. Photofrin (PF) was entrapped in multilammelar liposomes. Mice implanted with a human gastric cancer xenograft, were divided into a PF group and a liposomal photofrin (LPF) group and intravenously administered 10 mg/kg of PF or LPF (as a dose of PF), respectively. At 8 h after injection PF level in tumor tissue in the LPF group was significantly higher level by 2.4-fold of that in the PF group, whereas the PF levels in the skin were almost equal. Irradiation was performed with the excimer dye laser at 150 mW/cm(2), total dose 40 J, at 8 h after PF or LPF administration. The results revealed that the volume of necrotic tumor tissue was significantly higher in the LPF group than in the PF group. The apoptotic index of the tumor was also significantly higher in the LPF group. In conclusion, the liposomalization of the photosensitizer increased its tumor accumulation, with a resulting enhancement of the therapeutic effect of PDT.

  14. Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy.

    Science.gov (United States)

    Tutka, Piotr; Zatoński, Witold

    2006-01-01

    Cytisine, a natural plant alkaloid, has been marketed in Central and Eastern Europe for over 40 years for the clinical management of smoking cessation. Despite the fact that cytisine has been used by millions of smokers, its characteristics have not been reviewed in scientific literature in English, and presently existing clinical studies on its effectiveness and safety are insufficient to warrant licensing by modern standards. Understanding of the mechanism of cytisine action as a smoking cessation aid provides a necessary basis for conducting clinical trials to confirm its efficacy as an optimal antismoking therapy. Hereafter, we present a review of current knowledge about the pharmacokinetics, pharmacodynamics, toxicity, therapeutic efficacy and safety of cytisine, and about its derivatives that are under development. Recent pharmacological research has elucidated that the drug is a low efficacy partial agonist of alpha4beta2 nicotinic acetylcholine receptors, which are believed to be central to the effect of nicotine (NIC) on the reward pathway. The drug reduces the effects of NIC on dopamine release in the mesolimbic system when given alone, while simultaneously attenuating NIC withdrawal symptoms that accompany cessation attempts. Clinical studies on cytisine as a smoking cessation aid have demonstrated that the drug is effective and safe. Our recent uncontrolled trial has shown that a 12-month carbon monoxide-verified continuous abstinence rate following a standard course of treatment with cytisine with minimal behavioral support is similar (13.8%; N = 436) to that observed following treatment with NIC replacement therapy. Since cytisine exhibits a desirable pharmacological profile which makes it an attractive smoking cessation drug, it should be advanced to randomized clinical trials. However, more detailed preclinical studies on its pharmacokinetics and safety profile are required.

  15. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

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    Cohan S

    2016-09-01

    Full Text Available Stanley Cohan1,2,3 1Providence Multiple Sclerosis Center, 2Providence Brain and Spine Institute, 3Providence Health & Services, Portland, OR, USA Abstract: Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS, there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2 receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. Keywords: daclizumab, disease-modifying therapy, humanized monoclonal antibody, relapsing multiple sclerosis, therapeutic use

  16. Preventive and therapeutic efficacy of finasteride and dutasteride in TRAMP mice.

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    Alexander B Opoku-Acheampong

    Full Text Available BACKGROUND: The prostate cancer prevention trial (PCPT and Reduction by dutasteride of Prostate Cancer Events (REDUCE trial found that 5α-reductase (5αR inhibitors finasteride and dutasteride respectively, decreased prostate cancer prevalence but also increased the incidence of high-grade tumors. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have high 5αR1 and low 5αR2 expression. Because finasteride inhibits only 5αR2, we hypothesized that it would not be as efficacious in preventing prostate cancer development and/or progression in C57BL/6 TRAMP x FVB mice as dutasteride, which inhibits both 5αR1 and 5αR2. METHOD/PRINCIPAL FINDINGS: Six-week-old C57BL/6 TRAMP x FVB male mice were randomized to AIN93G control or pre- and post- finasteride and dutasteride diet (83.3 mg drug/kg diet groups (n =30-33 that began at 6 and 12 weeks of age, respectively, and were terminated at 20 weeks of age. The pre- and post- finasteride and dutasteride groups were designed to test the preventive and therapeutic efficacy of the drugs, respectively. Final body weights, genitourinary tract weights, and genitourinary tract weights as percentage of body weights were significantly decreased in the Pre- and Post-dutasteride groups compared with the control. The Post-dutasteride group showed the greatest inhibition of prostatic intraepithelial neoplasia progression and prostate cancer development. Surprisingly, the Post-dutasteride group showed improved outcomes compared with the Pre-dutasteride group, which had increased incidence of high-grade carcinoma as the most common and most severe lesions in a majority of prostate lobes. Consistent with our hypothesis, we found little benefit from the finasteride diets, and they increased the incidence of high-grade carcinoma. CONCLUSION: Our findings have commonalities with previously reported PCPT, REDUCE, and the Reduction by dutasteride of Clinical Progression Events in Expectant

  17. Implantable Doppler Probes for Postoperatively Monitoring Free Flaps: Efficacy. A Systematic Review and Meta-analysis

    OpenAIRE

    Chang, Tzu-Yen; Lee, Yao-Chou; Lin, You-Cheng; Wong, Stanley Thian-Sze; Hsueh, Yuan-Yu; Kuo, Yao-Lung; Shieh, Shyh-Jou; Lee, Jing-Wei

    2016-01-01

    Background: Although clinical assessment remains the gold standard for monitoring the circulation of free flaps, several adjunct techniques promote timely salvage by detecting circulation compromise early. The objective of this systematic review was to evaluate the efficacy of an implantable Doppler probe for postoperatively monitoring free flaps. Materials and Methods: English-language articles evaluating the efficacy of implantable Doppler probes compared with clinical assessment for postop...

  18. Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy.

    Science.gov (United States)

    Alam, Ahsan; Dahl, Neera K; Lipschutz, Joshua H; Rossetti, Sandro; Smith, Patricia; Sapir, Daniel; Weinstein, Jordan; McFarlane, Philip; Bichet, Daniel G

    2015-10-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials.

  19. Ultrasound and Microbubble Mediated Doxil Delivery in a Murine Breast Cancer Model: Therapeutic Efficacy Dependence on Tumor Growth Rate

    NARCIS (Netherlands)

    Seip, R.; Leyvi, E.; Raju, B.I.; Shi, W.T.; Bohmer, M.R.; Chlon, C.H.T.; Sio, C.F.; Reibling, K.; Swanson, T.

    2011-01-01

    Background, Motivation and Objective: Localized drug delivery couldimprove the therapeutic efficacy for treatment of pathological lesions and reduce toxic exposure to healthy organs and tissues. The objective is to develop image-guided, ultrasound-activated tumor chemotherapy with intravenously admi

  20. Supervisor Support as a Predictor of Burnout and Therapeutic Self-Efficacy in Therapists Working in ABA Schools

    Science.gov (United States)

    Gibson, Jennifer A.; Grey, Ian M.; Hastings, Richard P.

    2009-01-01

    Very little is known about factors potentially affecting the performance of therapists delivering applied behavior analysis (ABA) interventions for young children with autism. Eighty-one therapists working in ABA schools participated in a questionnaire study focused on their reports of burnout and perceived therapeutic self-efficacy in their work…

  1. Therapeutic efficacy of Lactobacillus acidophilus against bacterial isolates from burn wounds

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    Mohammed Sh. Jebur

    2010-12-01

    Full Text Available Background: Probiotics are live microorganisms which are mainly strains of Lactobacillus spp., Bifidobacterium spp. When administered in adequate amounts, these microorganisms offer a health benefit for the host. Probiotic organisms are also available commercially in milk, sour milk, ice cream and other foods. Aims: To identify bacterial species isolated from burn wounds, and also to evaluate (In-vitro the therapeutic efficacy of Lacto. acidophilus against these bacterial isolates. To compare this activity to other antibacterial agents which are used medically in the treatment of burn wound cases. Materials and Methods: Burn wound swabs were obtained from 50 patients who had been admitted to hospitals in Baghdad during August to November 2009. These swabs were inoculated onto enriched and differential culture media. Subcultures were performed on selective media. The necessary biochemical tests were conducted and the organisms identified using standard procedures. Susceptibility of isolated pathogens to local isolates Lacto. Acidophilus (with 1х108 cells/mL and 10 commonly used burn wounds antibiotics was examined using standard susceptibility testing. Results: Ninety different organisms were isolated. Gram-positive cocci accounted for 16 (17.7% and gram-negative bacilli for 74 (82.2% bacterial isolates. Pseudomonas aeruginosa 30(33.3% were the most commonly isolated organisms, followed by Escherichia coli, Enterobacter spp., Klebsiella spp., Proteus spp.(22.2,20,4.4,2.2%, respectively. Staphylococcus aureus isolates were performed in 8(8.8%. However, the incidence of Staphylococcus epidermidis was 2 (2.2%, while ß-haemolytic Streptococci was 4(4.4%. In susceptibility testing, Lacto. acidophilus had coverage against 90 (100% of 74 gram-negative and 16 of gram-positive bacteria tested. The coverage of the remaining 10 antibacterial agents used was different in their activity (resistance or sensitivity, which ranged between 50-100%. Conclusion

  2. Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs

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    Ildiko Barabasi

    2016-11-01

    Full Text Available Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs 1Ildikó BARABÁSI, 1Cristina ȘTEFǍNUȚ, 1Laurenţ OGNEAN 1University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400037, Manastur street, no.3-5, Cluj-Napoca, Romania *Corresponding author: lognean@yahoo.com   Keywords: dogs, erythrocyte concentrate, hematocrit, immune-mediated hemolytic anemia, transfusion therapy Introduction: The minimum dose of whole blood products as well as erythrocyte concentrate has been under a lot of debate, new equations for calculating the optimal dose being made up from a large variety of hematologists (Kisielewicz et al 2014; Helm and Knottenbelt, 2010; Gibson, 2007. Aim: The therapeutical efficacy of erythrocyte concentrates in dogs with different types of anemia by measuring the hematocrit level 6 hours after the transfusion and a complete blood count 5 days post-transfusion therapy. Materials and methods: Blood tests were performed with ADIVA hematological analyzer; the 6 hour post-transfusion hematocrit was determined by a micro hematocrit. On admission every patient received a routine blood test that included 40 hematological parameters and 21 biochemical parameters. In addition, a detailed examination of the blood smears was also performed by the ADIVA hematological analyzer with 26 parameters that mostly referred to red blood cell and white blood cell morphology. Blood typing was done using the RapidVet quick test kit. Patients received only type specific blood and to limit transfusion reaction occurrences, in addition, a crossmatch test was performed before every transfusion. Statistical analysis was accomplished with GraphPadInStat 3.0 and the graphical depiction of the obtained results was made using the Origin 8.5. graphics program. Results: Statistical analysis reveal that the total red blood cell count underwent very significant changes (p=0.0052 as well as the hemoglobin (p=0.0085. The hematocrit

  3. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

    Science.gov (United States)

    Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-05-01

    Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (∼141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

  4. Progress in Therapeutic Drug Monitoring of antibacterial a gents%抗菌药物的治疗药物监测进展

    Institute of Scientific and Technical Information of China (English)

    胡瑾瑜; 施耀国

    2001-01-01

    The safety and efficacy of antibiotics with a narrow treatment index and higher toxicity can be enhenced by practicing therapeutic d rug monitoring(TDM) and indiv idualized administration.In this paper,progress in TDM of antibacterial agents i n home and abroad was reviewed.%实行治疗药物监测(therapeutic drug monitoring ,TDM )进行给药方案个体化,可使治疗指数小、安全范围窄、毒性反应较大的抗菌药物的使用更 加安全、有效。本文对国内外有关抗菌药物TDM的进展作一综述,旨在推动抗菌药物的TDM在 我国的开展。

  5. Efficacy Outcome Selection in the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trials

    Science.gov (United States)

    Holubkov, Richard; Clark, Amy E.; Moler, Frank W.; Slomine, Beth S.; Christensen, James R.; Silverstein, Faye S.; Meert, Kathleen L.; Pollack, Murray M.; Dean, J. Michael

    2014-01-01

    Objectives The THAPCA trials will determine if therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition (VABS-II), in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during THAPCA protocol development. Design Consensus assessment of potential outcomes and evaluation timepoints. Methods We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Results Twelve months post-arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in VABS-II from pre-arrest level, measured as quasi-continuous with death and vegetative status being worst possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes due to easier interpretability, and favored outcomes based solely on post-arrest status, due to concerns about accurate parental assessment of pre-arrest status and differing clinical impact of a given VABS-II change depending on pre-arrest status. Simulations found only modest power loss from categorizing or dichotomizing quasi-continuous outcomes, due to high expected mortality. The primary outcome selected was survival with 12-month VABS-II no less than two standard deviations below a reference population mean (70 points), necessarily evaluated only among children with pre-arrest VABS-II ≥ 70. Two secondary efficacy outcomes, twelve-month survival and quasi-continuous VABS-II change from pre-arrest level, will be evaluated among all randomized children including those with compromised function pre-arrest. Conclusions Extensive discussion of optimal efficacy assessment timing, and of the

  6. The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients.

    Science.gov (United States)

    El-Najjar, Nahed; Jantsch, Jonathan; Gessner, André

    2017-08-28

    Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

  7. Therapeutic monitoring of vancomycin - doi 10.4025/actascihealthsci.v34i2.10617

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    Sergio Seiji Yamada

    2012-09-01

    Full Text Available The present study aimed to characterize admitted patients in a public hospital in the Northwestern region of Paraná State, which were subject to therapeutic monitoring of vancomycin during 2007 and 2008. The data were obtained by a retrospective study of patients’ medical records, from where we separated the laboratory results, medical prescriptions, gender, age, and diagnosis of patients submitted to therapeutic monitoring. Of the total of 38 patients, only eight (21.1% presented serum concentrations within recommended range, varying from 1.3 to 47.9 mg L-1. Concentrations above the reference value were observed in 22 patients (57.9%, and below the reference, in other eight patients (21.1%. The recommended serum concentrations at peak were obtained in only four patients (11.4%, higher than the recommended value in seven patients (20.0%, and lower, in 24 patients (68.6%. Only one patient (2.6% presented serum concentration within the reference values at both high and low dosages. Therefore, the results evidenced the importance of therapeutic monitoring of vancomycin, individualizing the dose for each patient, and reducing toxic or subtherapeutic effects of this antimicrobial substance.  

  8. Therapeutic Efficacy Analysis of Balancing Yin-yang Manipulation for Post-stroke Upper Limb Spasticity

    Institute of Scientific and Technical Information of China (English)

    Cui Hua-feng; Gao Guo-qiang; Wang Yan-li; Yu Xiao-hua; Guo Li; Ren Shuo

    2014-01-01

    Objective: To observe the effect of balancing yin-yang needling manipulation on post-stroke upper limb spasticity and changes of electromyography (EMG) after treatment. Methods: A total of 60 eligible cases were randomly allocated into an observation group and a control group, 30 in each group. Based on routine medication, cases in the control group were treated with conventional needling manipulation, whereas cases in the observation group were treated with balancing yin-yang manipulation. After the courses of treatment were completed, the therapeutic efficacies were evaluated using modified Ashworth scale and clinical spasticity index (CSI), coupled with the integrated electromyography (IEMG) and root mean square (RMS) value of biceps in passive flexion of the elbow joint during isokinetic testing recorded with the surface EMG. Results: The total effective rate in the observation group was 86.7%, versus 53.3% in the control group, showing a statistical significance (P Conclusion:Balancing yin-yang and conventional needling manipulations can both improve upper limb spasm and reduce CSI as well as IEMG and RMS values in stroke patients;however, balancing yin-yang manipulation is better than conventional manipulation in clinical effect.

  9. Therapeutic efficacy and immunological response of CCL5 antagonists in models of contact skin reaction.

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    Miriam Canavese

    Full Text Available Skin-infiltrating T-cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis, psoriasis and allergic contact dermatitis. These T-cells are attracted by several chemotactic factors including the chemokine CCL5/RANTES, a CC chemokine inducing both the migration and activation of specific leukocyte subsets. CCL5 has been found to be associated with various cell-mediated hypersensitive disorders such as psoriasis, atopic dermatitis and irritant contact dermatitis. We have used two antagonists, the first, Met-CCL5, a dual CCR1/CCR5 antagonist and the second, a variant in which GAG binding is abrogated, (44AANA(47-CCL5, which acts as a dominant negative inhibitor of CCL5. The antagonists were tested in two models of contact skin reaction. The first, irritant contact dermatitis (ICD is a pathological non-specific inflammatory skin condition arising from the release of pro-inflammatory cytokines by keratinocytes in response to haptens, usually chemicals. The second, contact hypersensitivity (CHS is a T-cell dependent model, mimicking in part the T-cell-mediated skin diseases such as psoriasis. In both models, the CCL5 antagonists showed therapeutic efficacy by reducing swelling by 50% as well as the reduction of soluble mediators in homogenates derived from challenged ears. These results demonstrate that blocking the receptor or the ligand are both effective strategies to inhibit skin inflammation.

  10. Therapeutic efficacy and safety of propylthiouracil in psoriasis: An open-label study

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    Pushpa Gnanaraj

    2011-01-01

    Full Text Available Background: Psoriasis is a common hyperproliferative disorder of the skin associated with significant morbidity. Most of the drugs used in psoriasis provide only a temporary relief, whereas they are riddled with potential toxicities and cost concerns. Hence, there is a constant need to explore newer, effective, orally administered, and cost-effective drugs with minimal adverse effects. In this scenario, propylthiouracil (PTU, an antithyroid thioureylene has been shown to be effective in psoriasis which satisfies the above criteria. Aim: The objective of our study is to assess the clinical efficacy of PTU in psoriasis. Methods: A total of 25 patients with plaque psoriasis were treated with oral PTU for 12 weeks. Clinical response was assessed using the "Psoriasis Area and Severity Index" (PASI score. Routine blood analyses and thyroid function tests were carried out periodically during the study. Results: Oral PTU produced significant clearing of lesions at 6 weeks and 12 weeks of the study period in all patients, as demonstrated by the reduction in PASI scores (33.9% in 6 weeks and 74.1% reduction in 12 weeks. Four patients experienced near complete clearing of the lesions. One patient developed mild elevation of liver enzymes which reversed on withdrawal of PTU. None of the patients had hypothyroidism or cytopenias. Conclusion: PTU significantly clears the lesions in psoriasis with minimal adverse effects. Hence, it can be considered as a therapeutic option in psoriasis, especially when the standard drugs cannot be used due to their toxicities or forbidding cost.

  11. Diagnostic efficacy and therapeutic impact of computed tomography in the evaluation of clinically suspected otosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Dudau, Cristina [King' s College Hospital NHS Foundation Trust, Department of Neuroradiology, London (United Kingdom); Salim, Fakhruddin; Jiang, Dan [Department of Otolaryngology, Head and Neck Surgery, Auditory Implantation Centre, London (United Kingdom); Connor, Steve E.J. [Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2017-03-15

    To assess the diagnostic efficacy and therapeutic impact of CT in evaluating patients with clinically suspected otosclerosis. CT scans performed over a 5-year period for clinically suspected otosclerosis were retrospectively reviewed. CT diagnoses were correlated with subsequent surgical management. For otosclerosis positive cases, clinically significant extensions of otosclerosis were correlated with audiometry and the diagnosis was correlated with surgical findings. Of 259 CT studies, 46 % of patients were positive, 49 % negative and 5 % equivocal for otosclerosis. A relevant alternative CT diagnosis was evident in 33 % of the negative studies. One targeted surgery was performed for every four CT studies. CT outcome influenced the decision to perform stapedectomy in 41 % CT-positive versus 4 % CT-negative patients. CT-positive ears for otosclerosis could not be predicted from baseline clinical or audiometric criteria. Those with endosteal extension demonstrated lower bone conduction thresholds presurgically. The positive predictive value of CT diagnosis of otosclerosis was 100 %. CT demonstrated a high rate of clinically relevant diagnoses in both CT-positive and -negative for otosclerosis patients, and this frequently influenced surgical management. CT also added value by demonstrating relevant extensions of the otosclerotic foci, some of which were predictive of audiometric parameters. (orig.)

  12. Predicting In Vivo Efficacy of Therapeutic Bacteriophages Used To Treat Pulmonary Infections

    Science.gov (United States)

    Henry, Marine; Lavigne, Rob

    2013-01-01

    The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain of Pseudomonas aeruginosa to compare the activities in vitro and in vivo of a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good correlation was found between in vitro and in vivo activity. While the remaining two bacteriophages were active in vitro, they were not sufficiently active in vivo under similar conditions to rescue infected animals. Based on the bioluminescence recorded at 2 and 8 h postinfection, we also define for the first time a reliable index to predict treatment efficacy. Our results showed that the bacteriophages isolated directly on the targeted host were the most efficient in vivo, supporting a personalized approach favoring an optimal treatment. PMID:24041900

  13. Therapeutic efficacy of artemether-lumefantrine for Plasmodium vivax infections in a prospective study in Guyana

    Directory of Open Access Journals (Sweden)

    Eibach Daniel

    2012-10-01

    Full Text Available Abstract Background In Guyana, chloroquine + primaquine is used for the treatment of vivax malaria. A worldwide increase of chloroquine resistance in Plasmodium vivax led to questioning of the current malaria treatment guidelines. A therapeutic efficacy study was conducted using artemether-lumefantrine + primaquine against P. vivax to evaluate a treatment alternative for chloroquine. Methods From 2009 to 2010, a non-controlled study in two hospitals in Guyana was conducted. A total 61 patients with P. vivax infection were treated with artemether-lumefantrine as a six-dose regimen twice a day for three days with additional 0.25 mg/kg/d primaquine at day 0 for 14 days. Clinical and parasitological parameters were followed on days 0,1,2,3,7,14 and 28 in agreement with WHO guidelines. Plasmodium vivax DNA from eight patients was analysed for pvmdr1, molecular marker of resistance. Results Artemether-lumefantrine cleared 100% of parasites on day 1, but two patients (3% had recurrence of parasites on day 28, suggesting relapse. No pvmdr1 Y976F polymorphism was detected. The treatment regimen was well tolerated. Conclusions In Guyana, artemether-lumefantrine represents an adequate treatment option against P. vivax when combined with primaquine. Availability of this alternative will be of great importance in case of emerging chloroquine resistance against P. vivax.

  14. 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.

  15. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

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    K. M. Maheswari

    2014-01-01

    Full Text Available The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs of Amlodipine Besylate (AMLO to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC and methyl cellulose (MC along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30, and sodium lauryl sulphate (SLS as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  16. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy.

    Science.gov (United States)

    Maheswari, K M; Devineni, Pavan Kumar; Deekonda, Sravanthi; Shaik, Salma; Uppala, Naga Pravallika; Nalluri, Buchi N

    2014-01-01

    The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  17. Optical drug monitoring: photoacoustic imaging of nanosensors to monitor therapeutic lithium in vivo.

    Science.gov (United States)

    Cash, Kevin J; Li, Chiye; Xia, Jun; Wang, Lihong V; Clark, Heather A

    2015-02-24

    Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes.

  18. Effect of telmisartan on the therapeutic efficacy of pitavastatin in high-fat diet induced dyslipidemic guinea pigs.

    Science.gov (United States)

    Xu, Cuihuan; Fang, Dailong; Chen, Xi; Xinyue, Li; Nie, Yu; Xie, Yafei; Ma, Yu; Deng, Senyi; Zhang, Zhi; Song, Xiangrong

    2015-09-05

    Angiotensin II-receptor blockers (ARBs), similar to HMG-CoA reductase inhibitors (statins), could improve lipid metabolism abnormalities. There might be some cross-talking pathways between statins and ARBs to produce additive beneficial effects on lipid metabolism in dyslipidemia. However, few studies investigate the effects of ARBs on the therapeutic efficacy of statins in dyslipidemia. The present study was designed to systematically evaluate the effects of telmisartan on the therapeutic efficacy of pitavastatin on lowering lipid level and reducing fat deposition by employing a dyslipidemia model, guinea pigs. 48 Male guinea pigs fed with high-fat diet were randomly grouped and treated with vehicle, telmisartan, pitavastatin or telmisartan/pitavastatin combinations. After treatment for eight weeks, telmisartan could significantly enhance the therapeutic efficacy of pitavastatin by extremely reducing body weight gain, weight of adipose tissue and adipocyte size. However, telmisartan/pitavastatin combinations could not further improve lipid levels on the basis of pitavastain, though single telmisartan markedly decreased triglyceride (TG) and slightly increased high density lipoprotein cholesterol (HDL-C). Moreover, telmisartan/pitavastatin combinations significantly upregulated the gene expression level of peroxisome proliferator-activated receptor (PPAR)-δ, but no effects on the expression of PPAR-α/γ, leptin and adiponectin compared to monotherapy. Taken together, our studies provided new evidences that telmisartan has an additive beneficial influence on decreasing fat deposition and weight gain through PPAR-δ pathway but cannot enhance the therapeutic efficacy of pitavastatin on lowering lipid levels. The combinational administration of telmisartan and pitavastatin could be a potential therapeutic strategy for dyslipidemia related obesity and worthy of further investigation in obese animal models. Copyright © 2015 Elsevier B.V. All rights

  19. Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats#

    Science.gov (United States)

    Thiyagarajan, Meenakshisundaram; Kaul, Chaman Lal; Sharma, Shyam Sundar

    2004-01-01

    Free radicals have been implicated in cerebral ischemia reperfusion (IR) injury. Massive production of nitric oxide and superoxide results in continuous formation of peroxynitrite even several hours after IR insult. This can produce DNA strand nicks, hydroxylation and/or nitration of cytosolic components of neuron, leading to neuronal death. Peroxynitrite decomposition catalysts 5,10,15,20-tetrakis(N-methyl-4′-pyridyl)porphyrinato iron (III) (FeTMPyP) and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (FeTPPS) have been demonstrated to protect neurons in in vitro cultures; however, their neuroprotective efficacy in cerebral IR injury has not been explored. In the present study, we investigated the efficacy and the therapeutic time window of FeTMPyP and FeTPPS in focal cerebral ischemia (FCI). FCI was induced according to the middle cerebral artery occlusion (MCAO) method. After 2 h of MCAO and 70 h of reperfusion, the extent of neurological deficits, infarct and edema volume were measured in Sprague–Dawley rats. FeTMPyP and FeTPPS were administered at different time points 2, 6, 9 and 12 h post MCAO. FeTMPyP and FeTPPS (3 mg kg−1, i.v.) treatment at 2 and 6 h post MCAO produced significant reduction in infarct volume, edema volume and neurological deficits. However, treatment at latter time points did not produce significant neuroprotection. Significant reduction of peroxynitrite in blood and nitrotyrosine in brain sections was observed on FeTMPyP and FeTPPS treatment. As delayed treatment of FeTMPyP and FeTPPS produced neuroprotection, we tested whether treatment had any influence over the apoptotic neuronal death. DNA fragmentation and in situ nick end-labeling assays showed that FeTMPyP and FeTPPS treatment reduced IR injury-induced DNA fragmentation. In conclusion, peroxynitrite decomposition catalysts (FeTMPyP and FeTPPS) produced prominent neuroprotection even if administered 6 h post MCAO and the neuroprotective effect is at least in

  20. Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.

    Science.gov (United States)

    Liu, Kai; Wang, Zhi-qi; Wang, Shi-jiang; Liu, Ping; Qin, Yue-hong; Ma, Yan; Li, Xiao-Chen; Huo, Zhi-Jun

    2015-01-01

    Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer

  1. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

    Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

  2. Therapeutic Efficacy of the Combined Extract of Herbal Medicine Against Infectious Bursal Disease in Chickens

    Directory of Open Access Journals (Sweden)

    Changbo Ou, Ningning Shi1, Qing Pan, Deyu Tian, Wenshu Zeng and Cheng He*

    2013-07-01

    Full Text Available Currently, infectious bursal disease (IBD is a highly contagious disease leading to huge economic losses in poultry industry. Our objective was to investigate potential therapeutic effects of the combined extracts of Rhizoma Dryopteridis crassirhizomatis and Fructus mume (RDCFM against IBDV infection. Seventy-two 4-week-old SPF chickens were randomly divided into six groups and inoculated intranasally with 0.2 ml of 102.5 EID50 of IBDV strain CJ801. Twenty-four hours post infection, the birds were orally administered with 400, 200 and 100 mg/kg BW of RDCFM, respectively, 125 mg/kg Astragalus polysaccharide (ASP and saline water, respectively for 5 days and then monitored daily for 10 days. Finally, the remaining birds were euthanized to collect the sera for detecting antibodies and immune organs for determining the immune organs index as well as virus loads. The herbal extracts improved survival rate and relative body gain rate. Virus loads in bursa of Fabricius in herbal treated groups decreased significantly while higher antibody levels were detected in the three RDCFM groups as compared to those of ASP and infection group. These results implied that chickens administered with 100-200 mg/kg of RDCFM for 5 days could improve protection against IBDV infection and RDCFM may be a promising alternative to ASP and egg yolk antibody.

  3. Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model

    Science.gov (United States)

    Dohare, Preeti; Garg, Puja; sharma, Uma; Jagannathan, NR; Ray, Madhur

    2008-01-01

    Background Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil). Method In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters. Results C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis. Conclusion Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons. PMID:18826584

  4. Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

    Science.gov (United States)

    Date, Abhijit A; Nagarsenker, Mangal S; Patere, Shilpa; Dhawan, Vivek; Gude, R P; Hassan, P A; Aswal, V; Steiniger, Frank; Thamm, Jana; Fahr, Alfred

    2011-06-01

    The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

  5. Efficacy and Safety of the Doxazosin Gastrointestinal Therapeutic System for the Treatment of Benign Prostate Hyperplasia

    Directory of Open Access Journals (Sweden)

    Guang-Huan Sun

    2010-10-01

    Full Text Available This study was carried out to obtain information on the efficacy and safety of the controlled release formulation of the doxazosin Gastrointestinal Therapeutic System (GITS in Taiwanese subjects with benign prostatic hyperplasia (BPH. Studies of doxazosin in Asian populations for this indication have lacked data particularly from Taiwan. This was an 8-week, post-marketing, open-label, non-comparative study. Eighty male subjects (mean age=64 years with BPH received doxazosin GITS 4 mg once daily. At week 4, subjects who achieved an increase in maximum urinary flow rate (Qmax of >3 mL/s and a >30% reduction in the total International Prostate Symptom Score (IPSS continued on doxazosin GITS 4 mg for the remaining 4 weeks; all other subjects were up-titrated to 8mg once daily. Change from baseline at weeks 4 and 8 (primary endpoint in IPSS and Qmax was evaluated using two-sided paired t tests for the intent-to-treat population. Safety was assessed throughout the study. A total of 53 (66.3% subjects completed the study. Baseline Qmax and IPSS were 10.7+3.4 mL/s and 20.6+5.4, respectively. At week 8, a significant increase from baseline in Qmax of 3.3+4.6 mL/s (95% confidence interval = 2.2-4.4, p< 0.001 and a significant decrease in total IPSS of −8.9 + 7.0 (95% confidence interval=−10.5 to −7.3, p< 0.001 was observed. The most common treatment-related adverse event was dizziness. Doxazosin GITS 4 mg per day (with an 8-mg titration step effectively improved symptoms of BPH. The results from this study provide further information for clinicians on the use of doxazosin GITS for the treatment of BPH, particularly in Taiwanese patients.

  6. Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys

    Science.gov (United States)

    Warren, Travis K.; Jordan, Robert; Lo, Michael K.; Ray, Adrian S.; Mackman, Richard L.; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C.; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S.; Van Tongeren, Sean A.; Garza, Nicole L.; Donnelly, Ginger; Shurtleff, Amy C.; Retterer, Cary J.; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P.; Grimes, Elizabeth; Welch, Lisa S.; Gomba, Laura; Wilhelmsen, Catherine L.; Nichols, Donald K.; Nuss, Jonathan E.; Nagle, Elyse R.; Kugelman, Jeffrey R.; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O.; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M.; Trancheva, Iva; Feng, Joy Y.; Baraskaus, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R.; Flint, Mike; McMullan, Laura K.; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L.; Spiropoulou, Christina F.; Lee, William A.; Nichol, Stuart T.; Cihlar, Tomas; Bavari, Sina

    2016-01-01

    Summary The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae1. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications

  7. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

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    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  8. Bacterial burden of worn therapeutic silver textiles for neurodermitis patients and evaluation of efficacy of washing.

    Science.gov (United States)

    Daeschlein, G; Assadian, O; Arnold, A; Haase, H; Kramer, A; Jünger, M

    2010-01-01

    To reduce pruritus and colonization with Staphylococcus aureus, textiles containing silver are increasingly used as therapeutic option for patients with atopic dermatitis (AD). While wearing such textiles, the contained silver is in close contact with the patient's skin. The silver serves two purposes: to reduce bacterial colonization of the skin, and to prevent contamination of the textile with ensuing growth of microorganisms. It is unknown whether the silver impregnation is able to reduce bacterial contamination of the textile during wearing and to prevent bacterial growth within the textile. The aim of this study was to investigate the bacterial contamination in textiles containing silver versus placebo worn by patients with AD and to determine the efficacy of processing worn textiles by manual and machine-based washing. Additionally, the effect of silver textiles on S. aureus and total bacterial counts colonizing the skin of AD patients was analyzed. The reduction factor of silver textile compared to placebo was 0.5 log steps against S. aureus and 0.4 log steps against total bacteria. Silver textiles exhibited significantly less S. aureus as well as total bacterial colonization after 2 days of wearing without washing, as compared with a placebo textile. On placebo textiles 385.6 +/- 63.5 CFU total bacteria and 236.5 +/- 49.9 CFU S. aureus, and on silver textiles 279.9 +/- 78.7 CFU total bacteria and 119.3 +/- 39.4 CFU S. aureus were found on the inner side of the textiles facing the neurodermitis lesions. However, the unexpectedly high residual contamination despite the silver exposure represents a potential risk as recontamination source of S. aureus that could maintain the proinflammatory process in AD. This contamination is nearly completely eliminated by machine-based washing at 60 degrees C using conventional washing powder. AD patients wearing silver textiles should change their used clothes at least daily and wash them in a washing machine at 60 degrees

  9. An Experimental Toxoplasma gondii Dose Response Challenge Model to Study Therapeutic or Vaccine Efficacy in Cats

    Science.gov (United States)

    Cornelissen, Jan B. W. J.; van der Giessen, Joke W. B.; Takumi, Katsuhisa; Teunis, Peter F. M.; Wisselink, Henk J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10), and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application. PMID:25184619

  10. Understanding Self-Efficacy for Alcohol Use: The Roles of Self-Monitoring and Hypothesized Source Variables

    OpenAIRE

    Walker, N. Robrina

    2002-01-01

    Self-efficacy for avoiding alcohol use predicts alcohol use after treatment. However, self-efficacy predicts outcome differentially depending on whether ratings are made before or after treatment. In order to increase the predictive validity of self-efficacy judgments, the hypothesized sources of self-efficacy were examined in the current study utilizing a college student population. Self-efficacy ratings for avoiding heavy drinking before and after self-monitoring of drinking behavior were e...

  11. Prognostic factors of the therapeutic efficacy of mTOR and VEGFR inhibitors in patients with metastatic renal cell carcinoma

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    Е. А. Voroshilova

    2015-01-01

    Full Text Available Background. Thorough study of the molecular genetic alterations in patients with hereditary and sporadic renal cell carcinoma (RCC enabled to reveal potential therapeutic targets - vascular endothelial growth factor (VEGF, platelet-derived growth factor (PDGF, growth factor receptors (VEGFR, PDGFR, EGFR, FGFR, mTOR signaling protein. Advances in targeted therapy treatment in the current therapeutic practice have brought a problem of its rational use and ultimately effective outcomes. The main solution of solving this problem is to establish independent clinical and laboratory prognostic factors and molecular markers which could predict the efficacy of targeted therapy.Objective – optimization of targeted therapy in patients with RCC by using both molecular and genetic prognostic factors as predictors of the treatment efficacy.Materials and methods. We assessed the level of mRNA expression of 13 potential target genes in primary tumor and metastatic site of patients suffering from metastatic RCC (n = 43 and evaluated the influence of the selected genes’ expression on the therapeutic efficacy of mTOR inhibitors and VEGFR inhibitors.Conclusion. VEGFR1 mRNA overexpression in metastatic site as well as mTOR and/or PI3K mRNA overexpression could be assessed as potential biomarkers in predicting the treatment efficacy of VEGFR inhibitors and mTOR inhibitors respectively. The higher expression of RAF1 mRNA and mTOR signaling pathway are not typical molecular alterations in patients with mRCC. RAF1 mRNA overexpression in metastatic site as well as activation of the alternative signaling pathway (RAS-RAF-MAPK in tumor cell are negative prognostic factors of the efficacy of targeted therapy. Activation of the signaling RAS-RAF-MAPK pathway in tumor cells is probably an alternative independent mechanism that “drives” tumor development in certain groups of patients.

  12. [Bioimpedance means of skin condition monitoring during therapeutic and cosmetic procedures].

    Science.gov (United States)

    Alekseenko, V A; Kus'min, A A; Filist, S A

    2008-01-01

    Engineering and technological problems of bioimpedance skin surface mapping are considered. A typical design of a device based on a PIC 16F microcontroller is suggested. It includes a keyboard, LCD indicator, probing current generator with programmed frequency tuning, and units for probing current monitoring and bioimpedance measurement. The electrode matrix of the device is constructed using nanotechnology. A microcontroller-controlled multiplexor provides scanning of interelectrode impedance, which makes it possible to obtain the impedance image of the skin surface under the electrode matrix. The microcontroller controls the probing signal generator frequency and allows layer-by-layer images of skin under the electrode matrix to be obtained. This makes it possible to use reconstruction tomography methods for analysis and monitoring of the skin condition during therapeutic and cosmetic procedures.

  13. Contraceptive efficacy of the personal hormone monitoring system Persona.

    Science.gov (United States)

    Trussell, J

    1999-07-01

    This is a commentary on the contraceptive effectiveness of the personal hormone-monitoring system Persona; it points out the various errors committed in computing method pregnancy rates. The modifications presented by Bonnar et al. on the incorrect procedure for computing method pregnancy rates are criticized as erroneous because the denominator includes cycles in which there is no risk of a method pregnancy according to the authors' algorithm for classifying pregnancy in an imperfect-use cycle. It is also claimed that the new exercise is a more complicated and less accurate way of computing for pregnancy rates by comparison with the simpler alternative. Since this new algorithm, used in the Persona system, is based on flawed logic, the annual risk of pregnancy is actually higher than the estimated 6% among women using Persona and having intercourse in each cycle except on red days.

  14. Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation

    Directory of Open Access Journals (Sweden)

    Liu K

    2015-10-01

    Full Text Available Kai Liu,1 Zhi-qi Wang,2 Shi-jiang Wang,3 Ping Liu,4 Yue-hong Qin,5 Yan Ma,3 Xiao-Chen Li,6 Zhi-Jun Huo7 1Department of Gastrointestinal Surgery, 2Department of Head and Neck Surgery, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 4Department of Pharmacy, 5Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, 6Department of Internal Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, 7Department of Breast Disease Center, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Abstract: Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA-conjugated silica nanoparticles (SiNPs to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage compared with only 20% for 5-FU/silica nanoparticles (SNP-treated group. The HA

  15. Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer

    Directory of Open Access Journals (Sweden)

    Li X

    2012-10-01

    Full Text Available Xiaolin Li,1,* Hua’e Xu,2,* Xinzheng Dai,3,4,* Zhenshu Zhu,5 Baorui Liu,6 Xiaowei Lu11Department of Geriatrics, 2Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 3Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, 4Liver Transplantation Center, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 5Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing; 6The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China*These authors contributed equally to this workAbstract: Paclitaxel (Ptx, one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL®. The current study reports the stable controlled release of Ptx/tetrandrine (Tet-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol–poly(caprolactone block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptx-loaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the

  16. Efficacy of a therapeutic strategy for eradication of Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Giuliana Sereni; Francesco Azzolini; Lorenzo Camellini; Debora Formisano; Francesco Decembrino; Veronica Iori; Cristiana Tioli

    2012-01-01

    AIM:To determine the efficacy of our therapeutic strategy for Helicobacter pylori (H.pylori) eradication and to identify predictive factors for successful eradication.METHODS:From April 2006 to June 2010,we retrospectively assessed 2428 consecutive patients (1025 men,1403 women; mean age 55 years,age range 18-92 years) with gastric histology positive for H.pylori infection referred to our unit for 13-C urea breath test (UBT),after first-line therapy with proton pump inhibitor (PPI) b.i.d.+ amoxicillin 1 g b.i.d.+ clarithromycin 500 mg b.i.d.for 7 d.Patients who were still positive to UBT were recommended a second-line therapy (PPI b.i.d.+amoxicillin 1 g b.i.d.+ tinidazole 500 mg b.i.d.for 14 d).Third choice treatment was empirical with PPI b.i.d.+amoxicillin 1 g b.i.d.+ levofloxacin 250 mg b.i.d.for 14 d.RESULTS:Out of 614 patients,still H.pylori-positive after first-line therapy,only 326 and 19 patients respectively rechecked their H.pylori status by UBT after the suggested second and third-line regimens."Per protocol" eradication rates for first,second and thirdline therapy were 74.7% (95% CI:72.7%-76.4%),85.3% (95% CI:81.1%-89.1%) and 89.5% (95% CI:74.9%-103%) respectively.The overall percentage of patients with H.pylori eradicated after two treatments was 97.8% (95% CI:97.1%-98.4%),vs 99.9% (95%CI:99.8%-100%) after three treatments.The study found that eradication therapy was most effective in patients with ulcer disease (P < 0.05,P =0.028),especially in those with duodenal ulcer.Smoking habits did not significantly affect the eradication rate.CONCLUSION:First-line therapy with amoxicillin and clarithromycin produces an H.pylori eradication rate comparable or superior to other studies and secondline treatment can still be triple therapy with amoxicillin and tinidazole.

  17. Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye.

    Science.gov (United States)

    Zheng, Wenjing; Ma, Mingming; Du, Ergang; Zhang, Zhengwei; Jiang, Kelimu; Gu, Qing; Ke, Bilian

    2015-11-01

    The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate‑buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain‑optical coherence tomography. Tear membrane break‑up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription‑quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultrastructure7 days after treatment. The percentages of apoptotic corneal‑ and Cj‑ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10

  18. The role of team goal monitoring in the curvilinear relationship between team efficacy and team performance.

    Science.gov (United States)

    Rapp, Tammy L; Bachrach, Daniel G; Rapp, Adam A; Mullins, Ryan

    2014-09-01

    In this research, we apply a team self-regulatory perspective to build and test theory focusing on the relationships between team efficacy and 2 key team performance criteria: a performance behavior (i.e., team effort) and a performance outcome (i.e., objective team sales). We theorize that rather than having a linear association, the performance benefits of team efficacy reach a point of inflection, reflective of too much of a good thing. Further, in an effort to establish a boundary condition of the inverted-U shaped relationship we predict, we also test the moderating role played by team goal monitoring in the nonmonotonic relationship between team efficacy and team performance. The results from a lagged field test, in which we collect multisource data from 153 technology sales teams, reveal a significant curvilinear association that is moderated by team goal monitoring behavior. Implications for theory and practice are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  19. Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St. John's wort.

    Science.gov (United States)

    Dasgupta, Amitava

    2008-04-01

    Herbal supplements can affect concentrations of therapeutic drugs measured in biological fluids by different mechanisms. Herbal products can either directly interfere with the methodology used in the measurement of drugs or indirectly interfere by altering the pharmacokinetics of coadministered drugs. The active components of Chan Su, Lu-Shen-Wan, Dan Shen, Asian and Siberian ginseng, oleander containing supplements, and Ashwagandha interfere with digoxin measurements by immunoassays, especially the polyclonal antibody-based immunoassays. Herbal supplements are sometimes contaminated with Western drugs causing drug toxicity. A therapeutic drug monitoring (TDM) service is very helpful for diagnosis of drug toxicity in such patients. Herbal products such as St. John's wort, a popular herbal antidepressant, increase the clearance of certain drugs either by increasing the activity of liver or intestinal cytochrome P-450 mixed-function oxidase or through modulation of the P-glycoprotein efflux pump. Significantly reduced concentrations of various therapeutic drugs such as digoxin, theophylline, cyclosporine, tacrolimus, tricyclic antidepressants, warfarin, and protease inhibitors can be observed due to interaction of these drugs with St. John's wort, causing treatment failure. On the other hand, a few drugs such as carbamazepine, mycophenolic acid, and procainamide do not show any interaction with St. John's wort. Understanding the effect of herbal products on TDM methodologies and identification of interactions between herbal products and drugs by TDM are very important clinically.

  20. NON INVASIVE THERAPEUTIC DRUG MONITORING OF PROPRANOLOL HYDROCHLORIDE BY REVERSE IONTOPHORESIS

    Directory of Open Access Journals (Sweden)

    Saini Vipin

    2012-04-01

    Full Text Available Therapeutic drug monitoring (TDM is highly required for drugs possessing narrow therapeutic index as a slight variation in the therapeutic range could result in no or low clinical efficiency or causes significant side effects or high risk of toxicity. In recent days, reverse iontophoresis technique has been attempted for the non invasive drug monitoring. Typically, it applies a low electric current through a pair of skin electrodes to promote the transport of both charged and neutral molecules. Transdermal iontophoretic extraction of propranolol was carried out and the study involves effect of different solvents having their different pH values on the iontophoretic extraction, effect of different voltages on the iontophoretic extraction, effect of different permeation enhancers on the permeability of propranolol hydrochloride and the effect of stratum corneum removal on the permeability of propranolol. Iontophoretic diffusion was carried out in vitro using full thickness rat skin. The efficient quantity of propranolol was collected at cathode by electromigration. The correlation between the extracted fluxes of propranolol and its subdermal concentration was found to be adequate. The values of extraction fluxes didn’t attain a steady state throughout the experiment. The decrease in the solvent pH doesn’t affect the transdermal extraction of propranolol. The decrease in the voltage causes diminishes in the iontophoretic fluxes. The application of permeation enhancers especially propylene glycol causes significantly increase in the iontophoretic fluxes of propranolol. Thus it is concluded that propranolol hydrochloride can be quantitatively extracted by reverse iontophoresis in varying conditions of subdermal concentration.

  1. Impact of acute otitis media pathogen shifts on the clinical efficacy of several antibiotics: a therapeutic outcomes model.

    Science.gov (United States)

    Canut, A; Martin-Herrero, J E; Maortua, H; Labora, A; Isla, A; Rodriguez-Gascon, A

    2009-08-01

    The aim of this study was to predict the clinical efficacy of different antimicrobials in the treatment of patients with acute otitis media (AOM), before and after the change in the proportion of middle ear pathogens observed after the introduction of the new conjugated heptavalent penumococcal vaccine (pPCV-7). The therapeutic Outcomes model was used to predict the likelihood of clinical success. According to this mathematical model the obtained rank order of predicted clinical efficacy was similar in the pre-PVC7 period and the post-PVC period. The results suggest that ceftriaxone and amoxicillin/clavulanate are the antibiotics with the highest predicted clinical efficacy, whereas cefaclor, azithromycin, erythromycin and clarithromycin are those with the lowest predicted clinical efficacy. The differences between antibiotics with good and those with low antibacterial activity were greater when only cases of bacterial AOM were considered. Antibiotics for which the highest clinical efficacy was predicted should maximize the likelihood of cure in outpatient antibiotic treatment of AOM.

  2. HIV/AIDS Knowledge, Self-Efficacy for Limiting Sexual Risk Behavior and Parental Monitoring.

    Science.gov (United States)

    Mahat, Ganga; Scoloveno, Mary Ann; Scoloveno, Robert

    2016-01-01

    The purpose of this study was to explore HIV/AIDS knowledge, self-efficacy for sexual risk behaviors, and parental monitoring in a sample of 140 7th and 9th grade adolescents studying in an urban high school in the United States. Further, the study examined differences in HIV/AIDS knowledge, self-efficacy and parental monitoring by grade and gender. This study also investigated the effectiveness of an HIV/AIDS peer education program, Teens for AIDS Prevention (TAP), on improving adolescents' HIV/AIDS knowledge. A quasi-experimental design was used to examine effects of the peer education program (TAP) on adolescents' HIV/AIDS knowledge. Pearson-product-moment correlation coefficients were calculated to examine the relationships among the variables. Independent t-tests were used to compare adolescents' HIV/AIDS knowledge, self-efficacy, and parental monitoring scores by grade and gender. Paired t-tests were used to determine differences in pre-intervention and post-intervention HIV/AIDS knowledge. The results showed that HIV/AIDS knowledge improved significantly in both 7th and 9th grade students after the intervention. HIV/AIDS knowledge was associated with self-efficacy; however it was not associated with parental monitoring. There were no significant differences in HIV/AIDS knowledge and self-efficacy by gender. However, there was a significant difference in parental monitoring by gender. Pediatric nurses are well-positioned to develop and implement evidence-based programs for adolescents. It is essential that pediatric nurses, in conjunction with other professionals and parent groups, take the initiative in implementing peer education programs in schools and community centers to promote healthy behaviors among adolescents. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pre-treatment antinuclear antibody positivity, therapeutic efficacy and persistence of biologics in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Codreanu Cătălin

    2016-06-01

    Full Text Available Introduction: Rheumatoid factor (RF and anti-citrullinated protein antibodies (ACPA are poor prognostic factors in rheumatoid arthritis (RA. The therapeutic implication of antinuclear antibody (ANA positivity in RA is still debated. The study aims to evaluate ANA positivity as a prognostic factor for the therapeutic response to biologics in RA.

  4. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy

    DEFF Research Database (Denmark)

    Battelino, T; Conget, I; Olsen, B

    2012-01-01

    The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.......The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes....

  5. Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Jeehoon Kang

    2016-11-01

    Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

  6. A photoacoustic tool for therapeutic drug monitoring of heparin (Conference Presentation)

    Science.gov (United States)

    Wang, Junxin; Hartanto, James; Jokerst, Jesse V.

    2017-03-01

    Heparin is used broadly in cardiac, pulmonary, surgical, and vascular medicine to treat thrombotic disorders with over 500 million doses per year globally. Despite this widespread use, it has a narrow therapeutic window and is one of the top three medication errors. The active partial thromboplastin time (PTT) monitors heparin, but this blood test suffers from long turnaround times, a variable reference range, and limited utility with low molecular weight heparin. Here, we describe an imaging technique that can monitor heparin concentration and activity in real time using photoacoustic spectroscopy via methylene blue as a simple and Federal Drug Agency-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood (R2>0.90). Clinically relevant concentrations were detected in blood with a heparin detection limit of 0.28 U/mL and a low molecular weight heparin (enoxaparin) detection limit of 72 μg/mL. We validated this imaging approach by correlation to the PTT (Pearson's r = 0.86; p<0.05) as well as with protamine sulfate treatment. To the best of our knowledge, this is the first report to use imaging data to monitor anticoagulation.

  7. [Therapeutic efficacies of neticonazole (SS717) cream and solution in experimental cutaneous Candida albicans infection of guinea pigs].

    Science.gov (United States)

    Maebashi, K; Itoyama, T; Uchida, K; Yamaguchi, H; Asaoka, T; Iwasa, A

    1993-10-01

    The therapeutic efficacies of 1% neticonazole (SS717) cream and solution on experimental cutaneous Candida albicans infection produced in prednisolone-treated guinea pigs were compared with those of 1% bifonazole (BFZ). Active preparations or blank vehicles were applied once daily for 3 consecutive days starting 5 days postinfection. Therapeutic effects were assessed on the basis of viable counts recovered from the infected loci 9 days postinfection. In animals treated with SS 717 or BFZ cream, a significant mycological improvement was observed when compared to untreated controls. A significant therapeutic efficacy of a SS717 cream compared to cream vehicle was also noted, while there was no significant difference in the recovery of Candida between the untreated control group and the cream vehicle-treated groups. The mycological result of the SS717 solution treated group was significantly superior to those of the untreated control group, the solution vehicle-treated group and the BFZ solution-treated group. The treatment with a solution vehicle or a BFZ solution appeared to lower, though not to a significant level, viable counts at the infected loci. These results led us to the conclusion that both SS717 cream and solution preparations exhibited significantly superior activity to that of BFZ in experimental cutaneous candidasis of guinea pigs.

  8. Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms

    OpenAIRE

    2014-01-01

    Genetic deletion of JAK2 in vivo shows that MPN cells remain fully dependent on JAK2 signaling for survival.Dual JAK2 targeting with JAK and HSP90 inhibitors offers increased efficacy in murine models and primary samples.

  9. Therapeutic Efficacy Observation on Acupoint Sticking for Edema Due to Chronic Cardiac Failure

    Institute of Scientific and Technical Information of China (English)

    Xu Jia-li

    2014-01-01

    Objective: To evaluate the therapeutic effect of acupoint sticking with Chinese herbs for edema due to chronic cardiac failure. Methods: One hundred and seventy patients in conformity with the diagnostic criteria of edema due to chronic cardiac failure were randomly divided into two groups, 85 cases in each group. The observation group was treated by oral administration of diuretics plus acupoint sticking with Chinese herbs. The control group was treated just by oral administration of diuretics same as the observation group. The therapeutic effects were evaluated after continuous intervention for 14 d. Results: The total effective rate was 90.6% in the observation group, remarkably higher than 67.1% in the control group. The difference of overall therapeutic effect between the two groups was statistically significant (P Conclusion: The therapeutic effect of acupoint sticking with Chinese herbs plus oral administration of diuretics is better than simple oral administration of diuretics in treatment of edema due to chronic cardiac failure.

  10. Impact of clinical decision support guidelines on therapeutic drug monitoring of gentamicin in newborns.

    Science.gov (United States)

    Fonzo-Christe, Caroline; Guignard, Bertrand; Zaugg, Claudia; Coehlo, Ana; Posfay-Barbe, Klara M; Gervaix, Alain; Desmeules, Jules; Rollason, Victoria; Combescure, Christophe; Corbelli, Regula; Rimensberger, Peter; Pfister, Riccardo; Bonnabry, Pascal

    2014-10-01

    Our institution's gentamicin dosing and therapeutic drug monitoring (TDM) practices for newborns were suspected to be very heterogeneous. Once-daily dosing (ODD) or extended-interval dosing (EID) and trough concentration measurement were recommended. Clinical decision support guidelines were developed and implemented as clinical decision support in the computerized prescriber order entry system. Impact on dosing, TDM practices, and blood sampling were evaluated. A 1-year retrospective historically controlled study before (April 2008-March 2009) and after the implementation of guidelines (January 2010-December 2010) for newborns ( 0.05). After implementation of the guidelines, an ODD/EID regimen was almost exclusively used (97.7% versus 61.6%, P Guideline implementation generated a sharp reduction in blood sampling. Clinical benefits of better gentamicin dosing and TDM practices were evident. Cost-effectiveness and clinical benefit of reduced blood sampling should be evaluated.

  11. Comparative analysis of therapeutic efficacy of 131I in different clinical stages postoperative patients with papillary thyroid carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li Zhao; Shuyao Zuo; Guoming Wang

    2012-01-01

    Objective: The aim of this study was to compare the effect of 131I therapy of different clinical stages in postopera-tive patients with papillary thyroid carcinoma (PTC). Methods: Eighty-seven PTC patients after surgery ablated with high doses of 131I from 2004 to 2010 were retrospectively reviewed. The efficacy of 131I therapy was assessed by three diagnostics that serum thyroglobulin (Tg) was normal or significantly reduced, 131I whole body scan (131I-WBS) was negative or the metas-tases shrank or the number of them decreased and new metastases was not found in cervical ultrasound examination. The χ2 test was used to analyze 3 factors which might affect the therapeutic efficacy of 131I in patients of different clinical period, including different surgical ways (total or subtotal thyroidectomy along with half or double sides neck lymph node dissection), age ( 0.25, P < 0.005, P < 0.01). The effective rate was 91.67% (44) in 48 cases undergoing total thyroidectomy; the effective rate was 53.85% (21) in 39 patients undergoing subtotal thyroidectomy. There was a significant difference between the two groups above by χ2 test (χ2 = 16.291; P < 0.005). Conclusion: The efficacy of 131I ablation of stage I and stage III in postoperative PTC patients was almost alike, while the efficacy of stage IV descended markedly. The results was mainly determined by residual thyroid tissue size because of different surgical modus.

  12. Design of a surface plasmon resonance immunoassay for therapeutic drug monitoring of amikacin.

    Science.gov (United States)

    Losoya-Leal, Adrian; Estevez, M-Carmen; Martínez-Chapa, Sergio O; Lechuga, Laura M

    2015-08-15

    The therapeutic drug monitoring (TDM) of pharmaceutical drugs with narrow therapeutic ranges is of great importance in the clinical setting. It provides useful information towards the enhancement of drug therapies, aiding in dosage control and toxicity risk management. Amikacin is an aminoglycoside antibiotic commonly used in neonatal therapies that is indicated for TDM due to the toxicity risks inherent in its use. Current techniques for TDM such as high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are costly, time consuming, and cannot be performed at the site of action. Over the last decades, surface plasmon resonance (SPR) biosensors have become increasingly popular in clinical diagnostics due to their ability to detect biomolecular interactions in real-time. We present an SPR-based competitive immunoassay for the detection of the antibiotic amikacin, suitable for TDM in both adults and neonates. We have obtained high specificity and sensitivity levels with an IC50 value of 1.4ng/mL and a limit of detection of 0.13ng/mL, which comfortably comply with the drug's therapeutic range. Simple dilution of serum can therefore be sufficient to analyze low-volume real samples from neonates, increasing the potential of the methodology for TDM. Compared to current TDM conventional methods, this SPR-based immunoassay can provide advantages such as simplicity, potential portability, and label-free measurements with the possibility of high throughput. This work is the foundation towards the development of an integrated, simple use, highly sensitive, fast, and point-of-care sensing platform for the opportune TDM of antibiotics and other drugs in a clinical setting.

  13. Assessment of therapeutic drug monitoring of vancomycin in elderly patients according to new guidelines.

    Science.gov (United States)

    Oh, Se Jin; Hong, Ki-Sook; Lee, Eun Jeong; Choi, Hee Jung; Kong, Kyoung Ae; Lee, Miae; Chung, Wha Soon

    2014-01-01

    Concerns regarding increasing microbial resistance to vancomycin have resulted in recommendations for a higher trough serum vancomycin concentration. This study aimed to assess the dosage guidelines targeting vancomycin trough concentrations of 15-20 mg/L. About 216 adult patients (age, >60 yr) were treated with intravenous vancomycin. The patients were divided into 2 groups according to their target vancomycin trough concentrations: the previous guideline group (n=108) treated with targeted vancomycin trough concentrations of 5-15 mg/L from Jan 2009 through April 2011 and the new guideline group (n=108) treated with targeted concentrations of 15-20 mg/L from November 2011 through July 2012. The 2 groups were not significantly different with respect to age, weight, initial serum creatinine, initial creatinine clearance, predictive trough levels, doses, serum drug concentrations, and area under the curve/minimal inhibitory concentrations. Regarding the proportions of vancomycin trough concentrations, the target range was achieved in 50% in the previous guideline group and in 16% in the new guideline group. In the previous and new guideline groups, the trough concentrations of 10-20 mg/dL were observed in 32.4% and 52.8% patients, respectively, and those of guideline group, the new guideline group showed higher proportions in the therapeutic range of 10-20 mg/L and lower proportions in trough concentrations therapeutic drug monitoring in the new guideline group was assessed as more effective.

  14. Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

    Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

  15. Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    Thomas L. Chenevert

    2002-10-01

    Full Text Available The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator of treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a non-volumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

  16. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-10-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies.

  17. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-01-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies. PMID:27721398

  18. Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India.

    Science.gov (United States)

    Bharti, Praveen K; Shukla, Man M; Ringwald, Pascal; Krishna, Sri; Singh, Pushpendra P; Yadav, Ajay; Mishra, Sweta; Gahlot, Usha; Malaiya, Jai P; Kumar, Amit; Prasad, Shambhu; Baghel, Pradeep; Singh, Mohan; Vadadi, Jaiprakash; Singh, Mrigendra P; Bustos, Maria Dorina G; Ortega, Leonard I; Christophel, Eva-Maria; Kashyotia, Sher S; Sonal, Gagan S; Singh, Neeru

    2016-10-13

    Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required. This was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450-680. A total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24-48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24-72 h). Additionally, no adverse event was

  19. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration.

    Science.gov (United States)

    Dolton, Michael J; Ray, John E; Chen, Sharon C-A; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-11-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml; P posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P posaconazole exposure (P posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure optimal systemic exposure.

  20. The default mode network as a biomarker for monitoring the therapeutic effects of meditation.

    Science.gov (United States)

    Simon, Rozalyn; Engström, Maria

    2015-01-01

    The default mode network (DMN) is a group of anatomically separate regions in the brain found to have synchronized patterns of activation in functional magnetic resonance imaging (fMRI). Mentation associated with the DMN includes processes such as mind wandering, autobiographical memory, self-reflective thought, envisioning the future, and considering the perspective of others. Abnormalities in the DMN have been linked to symptom severity in a variety of mental disorders indicating that the DMN could be used as a biomarker for diagnosis. These correlations have also led to the use of DMN modulation as a biomarker for assessing pharmacological treatments. Concurrent research investigating the neural correlates of meditation, have associated DMN modulation with practice. Furthermore, meditative practice is increasingly understood to have a beneficial role in the treatment of mental disorders. Therefore we propose the use of DMN measures as a biomarker for monitoring the therapeutic effects of meditation practices in mental disorders. Recent findings support this perspective, and indicate the utility of DMN monitoring in understanding and developing meditative treatments for these debilitating conditions.

  1. The default mode network as a biomarker for monitoring the therapeutic effects of meditation

    Directory of Open Access Journals (Sweden)

    Rozalyn eSimon

    2015-06-01

    Full Text Available The default mode network (DMN is a group of anatomically separate regions in the brain found to have synchronized patterns of activation in functional magnetic resonance imaging (fMRI. Mentation associated with the DMN includes processes such as mind wandering, autobiographical memory, self-reflective thought, envisioning the future, and considering the perspective of others. Abnormalities in the DMN have been linked to symptom severity in a variety of mental disorders indicating that the DMN could be used as a biomarker for diagnosis. These correlations have also led to the use of DMN modulation as a biomarker for assessing pharmacological treatments. Concurrent research investigating the neurocorrelates of meditation have associated DMN modulation with practice. Furthermore, meditative practice is increasingly understood to have a beneficial role in the treatment of mental disorders. Therefore we propose the use of DMN measures as a biomarker for monitoring the therapeutic effects of meditation practices in mental disorders. Recent findings support this perspective, and indicate the utility of DMN monitoring in understanding and developing meditative treatments for these debilitating conditions.

  2. EVALUATION OF BLOOD SAMPLING TIMES AND INDICATIONS FOR THERAPEUTIC DRUG MONITORING SERVICES

    Directory of Open Access Journals (Sweden)

    AISHAH HAMZAH

    2008-01-01

    Full Text Available The appropriateness of sampling times and indications for monitoring of serum drug concentrations for the purpose of therapeutic drug monitoring (TDM were evaluated at three hospitals on the east coast of Malaysia. Appropriateness criteria for indication and sampling were adapted from previously published criteria and with input from local TDM pharmacists. Six drugs were chosen, namely gentamicin, digoxin, carbamazepine, phenobarbital, phenytoin, and valproic acid. A total of 265 TDM requests were evaluated. Appropriateness of the indication for TDM ranged from 77.4% to 82%, while that for sampling ranged from 34.2% to 62.1%. There were no significant differences between the three hospitals in both categories of appropriateness. Among different drug groups, the percentage of appropriate indication was found to be highest with antiepileptic drugs. Antiepileptic drugs, however, had the lowest rate of appropriate sampling. Overall, findings from the three hospitals showed very encouraging results with almost 80% of the requests considered as appropriately indicated. However, the percentage of appropriateness of sampling was lower, and thus may require further investigation.

  3. A Case Report of Clonazepam Dependence: Utilization of Therapeutic Drug Monitoring During Withdrawal Period.

    Science.gov (United States)

    Kacirova, Ivana; Grundmann, Milan; Silhan, Petr; Brozmanova, Hana

    2016-03-01

    Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence.

  4. A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients.

    Science.gov (United States)

    De Francia, Silvia; Massano, Davide; Piccione, Francesca Maria; Pirro, Elisa; Racca, Silvia; Di Carlo, Francesco; Piga, Antonio

    2012-04-15

    We describe a new high performance liquid chromatography coupled with ultraviolet detection method for the quantification of plasma concentration of oral iron chelating agent deferasirox. A simple protein precipitation extraction procedure was applied on 500 μl of plasma aliquots. Chromatographic separation was achieved on a C18 reverse phase column and eluate was monitored at 295 nm, with 8 min of analytical run. This method has been validated following Food and Drug Administration procedures: mean intra and inter day variability was 4.64 and 10.55%; mean accuracy was 6.27%; mean extraction recovery 91.66%. Calibration curves ranged from 0.078125 to 40 μg/ml. Limit of quantification was set at 0.15625 while limit of detection at 0.078125 μg/ml. We applied methodology developed on plasma samples of thalassaemic patients treated with deferasirox, finding correlation between deferasirox plasma concentrations and serum ferritin levels. This methodology allowed a specific, sensitive and reliable determination of deferasirox, that could be useful to perform its therapeutic monitoring and pharmacokinetic studies in patients plasma.

  5. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Prev

  6. An audit of therapeutic drug monitoring services of anticonvulsants at a tertiary care hospital in India.

    Science.gov (United States)

    Taur, Santosh R; Kulkarni, Namrata B; Gogtay, Nithya J; Thatte, Urmila M

    2013-04-01

    Therapeutic drug monitoring (TDM) is an important adjunct to the treatment of epilepsy. However, few studies have actually correlated plasma levels of antiepileptic drugs (AEDs) with treatment response. The present audit aimed to study (i) the association between seizure control and number of AEDs, plasma AED concentration, and concomitant use of antitubercular drugs; (ii) the pattern of indications for TDM requisitions; and (iii) the association between referral for toxicity and plasma AED concentration. This observational and retrospective study was carried out to analyze the TDM data of patients referred between January 2008 and December 2011. As per the International League Against Epilepsy Task Force 2009, patients were categorized into responders and nonresponders. Plasma AED levels were interpreted as below, within, and above the reference range. Of 3206 TDM requisitions, 67% were monotherapy and 33% were 2 or more AEDs. Only 8% were responders as against 92% nonresponders. Of 95 patients on concomitant antituberculosis treatment, 72 were nonresponders, with odds ratio (95% confidence interval) 3.71 [2.19 to 6.23]. Breakthrough seizure (37%) was the most common indication followed by suspected toxicity and routine monitoring in 22% each and suspected nonadherence in 11% of the total requests. In 52% of patients, plasma levels were below the reference range, and they were equally distributed amongst responders and nonresponders. Among patients referred for suspected phenytoin toxicity, only 59% (50.6 to 67.8) had plasma concentrations above the reference range. TDM continues to remain an important tool to support dose individualization when the patient is receiving multiple AEDs or other drugs such as antitubercular medicines, to assess compliance, and to monitor and treat toxicity.

  7. Therapeutic Drug Monitoring in Neonatal HSV Infection on Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Funaki, Takanori; Miyata, Ippei; Shoji, Kensuke; Enomoto, Yuki; Sakamoto, Seisuke; Kasahara, Mureo; Miyairi, Isao

    2015-07-01

    Optimal acyclovir dosing under continuous renal replacement therapy (CRRT) in neonates is unknown. We monitored serum acyclovir levels and herpes simplex virus 1 (HSV-1) DNA levels in a neonate with disseminated HSV-1 infection and renal failure undergoing CRRT. A full-term, 5-day-old female presented with a 2-day history of lethargy and fever. She developed fulminant hepatitis and was diagnosed with HSV-1 infection by real-time polymerase chain reaction. Acyclovir was initiated at 60 mg/kg/day, which was lowered to 20 mg/kg/day because of development of renal failure. She was placed on continuous hemodialysis. Acyclovir dosing was adjusted according to serum acyclovir levels, and HSV-1 viral load was sequentially monitored. Semiquantification of serum HSV-1 levels was performed by real-time polymerase chain reaction. Acyclovir levels were measured by using liquid chromatography-tandem mass spectrometry. Acyclovir was administered at 20 mg/kg intravenously over 1 hour; peak concentration was 18.9 μg/mL. The half-life of acyclovir was estimated to be 2 to 3 h. Viral load remained high during dosing every 24 hours, with a decline of 0.17 log copies/24 hours. Acyclovir dosing was changed to 20 mg/kg/dose every 8 hours, with an average viral load decline of 0.44 log copies/24 hours. Despite the guideline recommendation of 24-hour redosing, acyclovir was dialyzed at a rate that resulted in suboptimal treatment. Individual therapeutic drug monitoring for acyclovir and dosing adjustment may be required to optimize therapy for patients undergoing CRRT. Copyright © 2015 by the American Academy of Pediatrics.

  8. Epidermal growth factor receptor-targeted antibody therapy - Mechanisms of action and modulators of therapeutic efficacy

    NARCIS (Netherlands)

    Lammerts van Bueren, Jeroen Jilles

    2008-01-01

    Cancer is an increasing disease in the world population, and in recent years there has been substantial interest in the development of novel therapeutic agents specifically targeting growth factor receptors on tumor cells. The epidermal growth factor receptor (EGFR) represents a tyrosine kinase cell

  9. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  10. Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system

    Science.gov (United States)

    DeRosa, F; Guild, B; Karve, S; Smith, L; Love, K; Dorkin, J R; Kauffman, K J; Zhang, J; Yahalom, B; Anderson, D G; Heartlein, M W

    2016-01-01

    DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated with lipids and lipid-like materials were developed for delivery of two separate mRNA transcripts encoding either human erythropoietin (hEPO) or factor IX (hFIX) protein. Dose-dependent protein production was observed for each mRNA construct. Upon delivery of hEPO mRNA in mice, serum EPO protein levels reached several orders of magnitude (>125 000-fold) over normal physiological values. Further, an increase in hematocrit (Hct) was established, demonstrating that the exogenous mRNA-derived protein maintained normal activity. The capacity of producing EPO in non-human primates via delivery of formulated mRNA was also demonstrated as elevated EPO protein levels were observed over a 72-h time course. Exemplifying the possible broad utility of mRNA drugs, therapeutically relevant amounts of human FIX (hFIX) protein were achieved upon a single intravenous dose of hFIX mRNA-loaded lipid nanoparticles in mice. In addition, therapeutic value was established within a hemophilia B (FIX knockout (KO)) mouse model by demonstrating a marked reduction in Hct loss following injury (incision) to FIX KO mice. PMID:27356951

  11. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy.

    Science.gov (United States)

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; Dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a "safer" approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments.

  12. Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana

    Directory of Open Access Journals (Sweden)

    Abuaku Benjamin

    2012-11-01

    Full Text Available Abstract Background In 2008, artemether - lumefantrine (AL and dihydroartemisinin - piperaquine (DHAP were added to artesunate - amodiaquine (AS-AQ as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. Methods The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. Results A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6 and 95.4% (95% CI: 90.3, 98.0, respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4 was significantly the lowest compared with 100% (95% CI: 93.2, 99.9 in the forest zone and 93.8% (95% CI: 77.8, 98.9 in the coastal zone (P = 0.017. Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. Conclusions The study has shown that AL remains efficacious in Ghana with

  13. Therapeutic efficacy evaluation of 111in-VNB-liposome on human colorectal adenocarcinoma HT-29/ luc mouse xenografts

    Science.gov (United States)

    Lee, Wan-Chi; Hwang, Jeng-Jong; Tseng, Yun-Long; Wang, Hsin-Ell; Chang, Ya-Fang; Lu, Yi-Ching; Ting, Gann; Whang-Peng, Jaqueline; Wang, Shyh-Jen

    2006-12-01

    The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and 111In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/ luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene ( luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm 3. The uptakes of 111In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm 3. The tumor/blood ratios of 111In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, 2.25 and 4.39, respectively, at 0, 5 and 10 mg/kg VNB. BLI showed that significant tumor control was achieved in the group of 10 mg/kg VNB ( 111In-VNB-liposome). WBAR also confirmed this result. In this study, we have demonstrated a non-invasive imaging technique with a luciferase reporter gene and BLI for evaluation of tumor treatment efficacy in vivo. The SCID mice bearing HT-29/ luc xenografts treated with 111In-VNB-liposome were shown with tumor reduction by this technique.

  14. Comparing therapeutic efficacy between ivermectin, selamectin, and moxidectin in canaries during natural infection with Dermanyssus gallinae.

    Science.gov (United States)

    Todisco, Gianluca; Paoletti, Barbara; Giammarino, Angelo; Manera, Maurizio; Sparagano, Olivier A E; Iorio, Raffaella; Giannella, Benedetta; Robbe, Domenico

    2008-12-01

    The aim of this study was to compare the efficacy of three spot-on drugs on canaries during Dermanyssus gallinae natural infections and during the breeding season. Three groups of canary couples (seven couples each) were included: group A was treated with ivermectin, B with selamectin, and C with moxidectin. All the drugs were administered topically infrascapularly. The parasitic charge was estimated before the treatment (t(0)) and after 8 (t(1)), 16 (t(2)), 24 (t(3)), and 32 (t(4)) days following the initial treatment. No significant differences were detected among the three tested drugs for the five repeats for each of the four mite stages (egg, larva, nymphs, and fed and unfed adults). With regard to the decrease in the mean numbers of red mites, ivermectin and selamectin exerted their efficacy at t(2), contrary to moxidectin at t(3).

  15. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    emulsion RT- PCR . Additional modifications were made to our epitope discovery workflow to increase efficacy of transcript and neoantigen candidate...resource of normal transcript expression levels across all tissues against which tumors are compared for identification of uniquely expressed...license via GitHub. Statistical analysis was carried out by our team to determining the false discovery rate of shared clonotypes, comparing those

  16. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy.

    Science.gov (United States)

    Lee, Dylan E; Ayoub, Nagi; Agrawal, Devendra K

    2016-03-09

    Mesenchymal stem cells (MSCs) (also known as multipotent mesenchymal stromal cells) possess the capacity for self-renewal and multi-lineage differentiation, and their ability to enhance cutaneous wound healing has been well characterized. Acting via paracrine interactions, MSCs accelerate wound closure, increase angiogenesis, promote resolution of wound inflammation, favorably regulate extracellular matrix remodeling, and encourage regeneration of skin with normal architecture and function. A number of studies have employed novel methods to amplify the delivery and efficacy of MSCs. Non-traditional sources of MSCs, including Wharton's jelly and medical waste material, have shown efficacy comparable to that of traditional sources, such as bone marrow and adipose tissue. The potential of alternative methods to both introduce MSCs into wounds and increase migration of MSCs into wound areas has also been demonstrated. Taking advantage of the associations between MSCs with M2 macrophages and microRNA, methods to enhance the immunomodulatory capacity of MSCs have shown success. New measures to enhance angiogenic capabilities have also exhibited effectiveness, often demonstrated by increased levels of proangiogenic vascular endothelial growth factor. Finally, hypoxia has been shown to have strong wound-healing potential in terms of increasing MSC efficacy. We have critically reviewed the results of the novel studies that show promise for the continued development of MSC-based wound-healing therapies and provide direction for continued research in this field.

  17. Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

    Science.gov (United States)

    Abdel-Raheem, Talal A; Méabed, Eman M H; Nasef, Ghada A; Abdel Wahed, Wafaa Y; Rohaim, Rania M A

    2016-10-01

    The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 μg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient.

  18. Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family

    Science.gov (United States)

    Shepard, H. Michael; Brdlik, Cathleen M.; Schreiber, Hans

    2008-01-01

    The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family–targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences. PMID:18982164

  19. Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action

    Directory of Open Access Journals (Sweden)

    Damal K

    2013-11-01

    Full Text Available Kavitha Damal, Emily Stoker, John F FoleyRocky Mountain Multiple Sclerosis Research Group, Salt Lake City, UT, USAAbstract: Multiple sclerosis (MS is a debilitating neurological disorder that affects nearly 2 million adults, mostly in their prime of youth. An environmental trigger, such as a viral infection, is hypothesized to initiate the abnormal behavior of host immune cells: to attack and damage the myelin sheath surrounding the neurons of the central nervous system. While several other pathways and disease triggers are still being investigated, it is nonetheless clear that MS is a heterogeneous disease with multifactorial etiologies that works independently or synergistically to initiate the aberrant immune responses to myelin. Although there are still no definitive markers to diagnose the disease or to cure the disease per se, research on management of MS has improved many fold over the past decade. New disease-modifying therapeutics are poised to decrease immune inflammatory responses and consequently decelerate the progression of MS disease activity, reduce the exacerbations of MS symptoms, and stabilize the physical and mental status of individuals. In this review, we describe the mechanism of action, optimal dosing, drug administration, safety, and efficacy of the disease-modifying therapeutics that are currently approved for MS therapy. We also briefly touch upon the new drugs currently under investigation, and discuss the future of MS therapeutics.Keywords: multiple sclerosis, immunomodulation, interferons, glatiramer acetate, monoclonal antibodies, dimethyl fumarate

  20. Novel therapeutic modalities and drug delivery in pancreatic cancer – an ongoing search for improved efficacy

    Directory of Open Access Journals (Sweden)

    Yuqing Zhang

    2012-12-01

    Full Text Available Pancreatic cancer is an incredibly challenging disease due to its high rates of resistance to traditional chemotherapy and radiotherapy. There has been little improvement in the prognosis of pancreatic cancer cases in the past decades, highlighting the crucial need for more effective therapeutic approaches. Erlotinib, an EGFR inhibitor, and gemcitabine, a nucleoside analog, are currently used in combination for chemotherapy treatment, but new developments in drug delivery systems using liposomes and nanoparticles may be promising new modalities for management of the disease. In addition to standard chemotherapeutic drugs, these delivery systems can be utilized to deliver therapeutic agents such as siRNA, oncolytic viruses, small molecule inhibitors, antibodies, and suicide genes. Further work is required to elucidate how ligands and antibodies could be used to enhance the targeted delivery of drugs, thus increasing specificity, improving stability, and reducing the effect of the drugs on healthy tissue. Despite significant preclinical data, there are currently very few clinical trials involving pancreatic cancer targeted drug delivery. This article summarizes current developments in targeted pancreatic cancer drug delivery, focusing on delivery systems, targets, and therapeutic agents.

  1. Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial.

    Science.gov (United States)

    Gotta, V; Widmer, N; Decosterd, L A; Chalandon, Y; Heim, D; Gregor, M; Benz, R; Leoncini-Franscini, L; Baerlocher, G M; Duchosal, M A; Csajka, C; Buclin, T

    2014-12-01

    This study assessed whether a cycle of "routine" therapeutic drug monitoring (TDM) for imatinib dosage individualization, targeting an imatinib trough plasma concentration (C min) of 1,000 ng/ml (tolerance: 750-1,500 ng/ml), could improve clinical outcomes in chronic myelogenous leukemia (CML) patients, compared with TDM use only in case of problems ("rescue" TDM). Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5 years. Patients were allocated 1:1 to "routine TDM" or "rescue TDM." The primary endpoint was a combined outcome (failure- and toxicity-free survival with continuation on imatinib) over 1-year follow-up, analyzed in intention-to-treat (ISRCTN31181395). Among 56 patients (55 evaluable), 14/27 (52 %) receiving "routine TDM" remained event-free versus 16/28 (57 %) "rescue TDM" controls (P = 0.69). In the "routine TDM" arm, dosage recommendations were correctly adopted in 14 patients (median C min: 895 ng/ml), who had fewer unfavorable events (28 %) than the 13 not receiving the advised dosage (77 %; P = 0.03; median C min: 648 ng/ml). This first target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" because of small patient number and surprisingly limited prescriber's adherence to dosage recommendations. Favorable outcomes were, however, found in patients actually elected for target dosing. This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions. The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents.

  2. Electrochemical microfluidic chip based on molecular imprinting technique applied for therapeutic drug monitoring.

    Science.gov (United States)

    Liu, Jiang; Zhang, Yu; Jiang, Min; Tian, Liping; Sun, Shiguo; Zhao, Na; Zhao, Feilang; Li, Yingchun

    2017-05-15

    In this work, a novel electrochemical detection platform was established by integrating molecularly imprinting technique with microfluidic chip and applied for trace measurement of three therapeutic drugs. The chip foundation is acrylic panel with designed grooves. In the detection cell of the chip, a Pt wire is used as the counter electrode and reference electrode, and a Au-Ag alloy microwire (NPAMW) with 3D nanoporous surface modified with electro-polymerized molecularly imprinted polymer (MIP) film as the working electrode. Detailed characterization of the chip and the working electrode was performed, and the properties were explored by cyclic voltammetry and electrochemical impedance spectroscopy. Two methods, respectively based on electrochemical catalysis and MIP/gate effect were employed for detecting warfarin sodium by using the prepared chip. The linearity of electrochemical catalysis method was in the range of 5×10(-6)-4×10(-4)M, which fails to meet clinical testing demand. By contrast, the linearity of gate effect was 2×10(-11)-4×10(-9)M with remarkably low detection limit of 8×10(-12)M (S/N=3), which is able to satisfy clinical assay. Then the system was applied for 24-h monitoring of drug concentration in plasma after administration of warfarin sodium in rabbit, and the corresponding pharmacokinetic parameters were obtained. In addition, the microfluidic chip was successfully adopted to analyze cyclophosphamide and carbamazepine, implying its good versatile ability. It is expected that this novel electrochemical microfluidic chip can act as a promising format for point-of-care testing via monitoring different analytes sensitively and conveniently.

  3. Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia

    Directory of Open Access Journals (Sweden)

    Ibrahim MI

    2014-03-01

    Full Text Available Background: Therapeutic drug monitoring (TDM makes use of serum drug concentrations as an adjunct to decision-making. Preliminary data in our hospital showed that approximately one-fifth of all drugs monitored by TDM service were gentamicin. Objective: In this study, we evaluated the costs associated with providing the service in patients with bronchopneumonia and treated with gentamicin. Methods: We retrospectively collected data from medical records of patients admitted to the Hospital Universiti Sains Malaysia over a 5-year period. These patients were diagnosed with bronchopneumonia and were on gentamicin as part of their treatment. Five hospitalisation costs were calculated; (i cost of laboratory and clinical investigations, (ii cost associated with each gentamicin dose, (iii fixed and operating costs of TDM service, (iv cost of providing medical care, and (v cost of hospital stay during gentamicin treatment. Results: There were 1920 patients admitted with bronchopneumonia of which 67 (3.5% had TDM service for gentamicin. Seventy-three percent (49/67 patients were eligible for final analysis. The duration of gentamicin therapy ranged from 3 to 15 days. The cost of providing one gentamicin assay was MYR25, and the average cost of TDM service for each patient was MYR104. The average total hospitalisation cost during gentamicin treatment for each patient was MYR442 (1EUR approx. MYR4.02. Conclusion: Based on the hospital perspective, in patients with bronchopneumonia and treated with gentamicin, the provision of TDM service contributes to less than 25% of the total cost of hospitalization.

  4. Correlation between macrolide lung pharmacokinetics and therapeutic efficacy in a mouse model of pneumococcal pneumonia.

    Science.gov (United States)

    Veber, B; Vallée, E; Desmonts, J M; Pocidalo, J J; Azoulay-Dupuis, E

    1993-09-01

    The correlation between the pharmacokinetics of erythromycin, roxithromycin, clarithromycin, spiramycin and azithromycin and their efficacy was investigated in two pneumococcal pneumonia models. Female Swiss and C57B1/6 mice were infected with Streptococcus pneumoniae strain P4241 by the intratracheal per oral route. This virulent strain produces acute pneumonia with death within 3-4 days (Swiss mice), or subacute pneumonia with death within 10 days (C57B1/6 mice) in untreated mice and the outcome of the disease is closely related to progressive weight loss. Swiss mice received three doses of each macrolide 50 mg/kg bd beginning 18 h post-infection. C57B1/6 mice received three doses of each macrolide 25 mg/kg, bd (except azithromycin was 12.5 mg/kg bd) beginning 48 h post-infection. Cure rates were evaluated on the basis of body weight variations recorded daily after the end of treatment. Pharmacokinetic parameters were determined in infected and non-infected mice after a single dose of each macrolide 50 mg/kg sc. The pharmacokinetics of azithromycin was also determined in leucopenic Swiss mice. We observed a hierarchy of in-vivo efficacy as follows: azithromycin > spiramycin = clarithromycin > roxithromycin = erythromycin which did not correlate with in-vitro MIC or MBC. The same hierarchy was found in terms of the lung T1/2. Lung T1/2s of macrolides could thus be predictive of their efficacy in respiratory tract infections. A reduced tissue AUC of azithromycin was seen in leucopenic mice suggesting leucocytes may help transport macrolides to sites of infection.

  5. Insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children

    NARCIS (Netherlands)

    van der Elst, Kim CM; Pereboom, Marieke; van den Heuvel, Edwin R; Kosterink, Jos G W; Scholvinck, Elisabeth H.; Alffenaar, Jan-Willem C

    2014-01-01

    Background. Fluconazole is recommended as first-line treatment in invasive candidiasis in children and infants. Although timely achievement of adequate exposure of fluconazole improves outcome, therapeutic drug monitoring is currently not recommended. Methods. We conducted a retrospective study of c

  6. Method for therapeutic drug monitoring of azole antifungal drugs in human serum using LC/MS/MS

    NARCIS (Netherlands)

    Alffenaar, J. W. C.; Wessels, A. M. A.; van Hateren, K.; Greijdanus, B.; Kosterink, J. G. W.; Uges, D. R. A.

    2010-01-01

    Fungal infections occur in immunocompromised patients. Azole antifungal agents are used for the prophylaxis and treatment of these infections. The interest in therapeutic drug monitoring azole agents has increased over the last few years. Inter- and intra-patient variability of pharmacokinetics,

  7. Reduced chance of hearing loss associated with Therapeutic Drug Monitoring of Aminoglycosides in the treatment of Multidrug Resistant Tuberculosis

    NARCIS (Netherlands)

    van Altena, R; Dijkstra, J.A.; van der Meer, M E; Borjas Howard, J F; Kosterink, J G W; van Soolingen, D; van der Werf, T S; Alffenaar, J W C

    2017-01-01

    Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to

  8. Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: translating TNF-ɑ experience to oncology

    NARCIS (Netherlands)

    Oude Munnink, T.H.; Henstra, M.J.; Segerink, L.I.; Movig, K.L.L.; Brummelhuis-Visser, P.

    2016-01-01

    Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient varia

  9. Validation of limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring - is a separate validation group required?

    NARCIS (Netherlands)

    Proost, J. H.

    2007-01-01

    Objective: Limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring are usually validated in a separate group of patients, according to published guidelines. The aim of this study is to evaluate the validation of LSM by comparing independent validation with cross-validation us

  10. Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

    NARCIS (Netherlands)

    Hofman, Susan; Bolhuis, Mathieu S.; Koster, Remco A.; Akkerman, Onno W.; van Assen, Sander; Stove, Christophe; Alffenaar, Jan-Willem C.

    2015-01-01

    Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample p

  11. Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination.

    Science.gov (United States)

    Llopiz, Diana; Aranda, Fernando; Díaz-Valdés, Nancy; Ruiz, Marta; Infante, Stefany; Belsúe, Virginia; Lasarte, Juan José; Sarobe, Pablo

    2016-02-01

    Blocking antibodies against immunosuppressive molecules have shown promising results in cancer patients. However, there are not enough data to define those conditions dictating treatment efficacy. In this scenario, IL-10 is a cytokine with controversial effects on tumor growth. Thus, our aim was to characterize in which setting IL-10 blockade may potentiate the beneficial effects of a therapeutic vaccine In the IL-10-expressing B16-OVA and TC-1 P3 (A15) tumor models, therapeutic vaccination with tumor antigens plus the TLR7 ligand Imiquimod increased IL-10 production. Although blockade of IL-10 signal with anti-IL-10R antibodies did not inhibit tumor growth, when combined with vaccination it enhanced tumor rejection, associated with stronger innate and adaptive immune responses. Interestingly, a similar enhancement on immune responses was observed after simultaneous vaccination and IL-10 blockade in naive mice. However, when using vaccines containing as adjuvants the TLR3 ligand poly(I:C) or anti-CD40 agonistic antibodies, despite tumor IL-10 expression, anti-IL-10R antibodies did not provide any beneficial effect on tumor growth and antitumor immune responses. Of note, as opposed to Imiquimod, vaccination with this type of adjuvants did not induce IL-10 and correlated with a lack of in vitro IL-10 production by dendritic cells (DC). Finally, in B16-OVA-bearing mice, blockade of IL-10 during therapeutic vaccination with a multiple adjuvant combination (MAC) with potent immunostimulatory properties but still inducing IL-10 led to superior antitumor immunity and complete tumor rejection. These results suggest that for therapeutic antitumor vaccination, blockade of vaccine-induced IL-10 is more relevant than tumor-associated IL-10.

  12. Therapeutic efficacy and anti-inflammatory effect of ramelteon in patients with insomnia associated with lower urinary tract symptoms

    Directory of Open Access Journals (Sweden)

    Shimizu N

    2013-05-01

    Full Text Available Nobutaka Shimizu,1 Masahiro Nozawa,1 Koichi Sugimoto,2 Yutaka Yamamoto,1 Takafumi Minami,1 Taiji Hayashi,1 Kazuhiro Yoshimura,1 Tokumi Ishii,1 Hirotsugu Uemura11Department of Urology, Faculty of Medicine, Kinki University, Osaka, 2Department of Urology, Sakai Hospital, Faculty of Medicine, Kinki University, Osaka, JapanObjectives: This study was conducted to examine the therapeutic efficacy and anti-inflammatory effect of ramelteon in elderly patients with insomnia associated with lower urinary tract symptoms (LUTS, who visited our urology department.Methods: The study included 115 patients (102 men, 13 women who scored ≥4 on the Athens Insomnia Scale and who wished to receive treatment. The assessment scales for therapeutic efficacy included the International Prostate Symptom Score (IPSS for LUTS and the Insomnia Severity Index (ISI for sleep disorders. The high-sensitivity C-reactive protein (hs-CRP test was used to an objective assessment. The patients were treated with ramelteon (8 mg/day for an average of 10 weeks and were then reexamined using the questionnaires and hs-CRP test to evaluate therapeutic efficacy.Results: IPSS total scores declined significantly from 11.39 ± 8.78 to 9.4 ± 7.72. ISI total scores improved significantly from 11.6 ± 5.2 to 9.2 ± 5.3 (P < 0.0001. The levels of hs-CRP decreased significantly from 0.082 (standard deviation [SD] upper limit, 0.222; SD lower limit, −0.059 to 0.06 (SD upper limit, 0.152; SD lower limit, −0.032. The ISI scores ≥ 10 (n = 51 showed a weak correlation with the hs-CRP levels.Conclusion: Ramelteon had a systemic anti-inflammatory effect and improved sleep disorders and LUTS, suggesting that it may be a useful treatment for patients with LUTS-associated insomnia.Keywords: sleep disorders, inflammation, lower urinary tract symptoms, ramelteon

  13. Safety and therapeutic efficacy of adoptive p53-specific T cell antigen receptor (TCR) gene transfer

    OpenAIRE

    2014-01-01

    Immunotherapy with T cells genetically modified by retroviral transfer of tumor-associated antigen (TAA)-specific T cell receptors (TCR) is a promising approach in targeting cancer. Therefore, using a universal TAA to target different tumor entities by only one therapeutic approach was the main criteria for our TAA-specific TCR. Here, an optimized (opt) αβ-chain p53(264-272)-specific and an opt single chain (sc) p53(264-272)-specific TCR were designed, to reduce mispairing reactions of endoge...

  14. Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring

    Science.gov (United States)

    Manicke, Nicholas Edward; Abu-Rabie, Paul; Spooner, Neil; Ouyang, Zheng; Cooks, R. Graham

    2011-09-01

    A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

  15. Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure

    Directory of Open Access Journals (Sweden)

    Neelima Mishra

    2016-01-01

    Interpretation & conclusion: Till 2012, India′s national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.

  16. Breath ketone testing: a new biomarker for diagnosis and therapeutic monitoring of diabetic ketosis.

    Science.gov (United States)

    Qiao, Yue; Gao, Zhaohua; Liu, Yong; Cheng, Yan; Yu, Mengxiao; Zhao, Lingling; Duan, Yixiang; Liu, Yu

    2014-01-01

    Acetone, β -hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and β -hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (-), 2 (±), 3 (+), 4 (++), or 5 (+++) according to urinary ketone concentrations. There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis.

  17. Individual monitoring in nuclear medicine therapeutic procedures using extremity dosemeters LiF(Mg, Cu, P).

    Science.gov (United States)

    Sarti, G; Del Dottore, F; Fabbri, C; Tassinari, L; Pagan, S; Rustignoli, M; Motta, P

    2011-03-01

    Unsealed beta-gamma-emitting sources are used (15 GBq (90)Y each session) in nuclear medicine therapeutic procedures. Inside the manipulation cell and while giving the injection to the patient, the skin exposure is very high; electron radiation field is not homogeneous and thus the exposure of the extremities is not uniform. Particular individual monitoring is adopted: single thermoluminescence dosemeter, wrapped in polyethylene film and placed on an adhesive tape, is positioned on the tip of the fingers; 6-10 dosemeters are assigned to each operator per session. The energy and angle response is studied for X-ray spectra, (90)Sr/Y and (204)Tl--a unique mean calibration factor is calculated in order to estimate H(p)(0.07). Performance of dosemeter is analysed according to ISO 62387-1(2007) and the combined uncertainty (calculated using the Monte Carlo method) results lie in the order of 11 %. This method reveals the critical step of manipulation and administration and ensures that dose limits are not exceeded.

  18. Lipidomics: potential role in risk prediction and therapeutic monitoring for diabetes and cardiovascular disease.

    Science.gov (United States)

    Meikle, Peter J; Wong, Gerard; Barlow, Christopher K; Kingwell, Bronwyn A

    2014-07-01

    Lipidomics has developed rapidly over the past decade to the point where clinical application may soon be possible. Developments including high throughput technologies enable the simultaneous quantification of several hundred lipid species, thereby providing a global assessment of lipid metabolism. Given the key role of lipids in the pathophysiology of diabetes and cardiovascular disease, lipidomics has the potential to: i) Significantly improve prediction of future disease risk, ii) Inform on mechanisms of disease pathogenesis, iii) Identify patient groups responsive to particular therapies and iv) More closely monitor response to therapy. Lipidomic analyses of both whole plasma and lipoprotein subfractions are integral to the current initiative to understand the relationships between lipoprotein composition and function and how these are affected by disease and treatment. This approach will not only aid in appropriate targeting of existing lipid lowering therapies such as statins and fibrates, but will be important in unravelling the controversies surrounding HDL-based therapies which have failed in clinical trials to date. The ultimate utility of lipidomics to clinical practice will depend firstly on the ability of risk prediction models incorporating lipidomic parameters to significantly improve upon conventional clinical risk markers in predicting future disease risk. Secondly, for widespread application, lipidomic-based measurements must be practical and accessible through standard pathology laboratories. This review will cover developments in lipidomics including methodology, bioinformatics/statistics, insights into disease pathophysiology, the effect of therapeutic interventions, the role of large clinical outcome trials in validating lipidomic approaches to patient management and potential applications in clinical practice.

  19. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  20. Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

    Science.gov (United States)

    Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

    2017-03-01

    Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

  1. Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Wolfgang Kruis; Robert L(o)fberg; Axel Dignass; Elisabeth Steinhagen-Thiessen; Julia Morgenstern; Joachim M(o)ssner; Stephan Schreiber; Maurizio Vecchi; Alberto Malesci; Max Reinshagen

    2005-01-01

    AIM:To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy.METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk).Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn(R), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life(IBDQ), and laboratory tests.RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01)at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia.CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

  2. Therapeutic efficacy and toxicity of {sup 225}Ac-labelled vs. {sup 213}Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Essler, Markus; Gaertner, Florian C.; Blechert, Birgit; Senekowitsch-Schmidtke, Reingard; Seidl, Christof [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Neff, Frauke [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-04-15

    Targeted delivery of alpha-particle-emitting radionuclides is a promising novel option in cancer therapy. We generated stable conjugates of the vascular tumour-homing peptide F3 both with {sup 225}Ac and {sup 213}Bi that specifically bind to nucleolin on the surface of proliferating tumour cells. The aim of our study was to determine the therapeutic efficacy of {sup 225}Ac-DOTA-F3 in comparison with that of {sup 213}Bi-DTPA-F3. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were determined via clonogenic assays. The therapeutic efficacy of both constructs was assayed by repeated treatment of mice bearing intraperitoneal MDA-MB-435 xenograft tumours. Therapy was monitored by bioluminescence imaging. Nephrotoxic effects were analysed by histology. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were 53 kBq/ml and 67 Bq/ml, respectively. The median survival of control mice treated with phosphate-buffered saline was 60 days after intraperitoneal inoculation of 1 x 10{sup 7} MDA-MB-435 cells. Therapy with 6 x 1.85 kBq of {sup 225}Ac-DOTA-F3 or 6 x 1.85 MBq of {sup 213}Bi-DTPA-F3 prolonged median survival to 95 days and 97 days, respectively. While F3 labelled with short-lived {sup 213}Bi (t{sub 1/2} 46 min) reduced the tumour mass at early time-points up to 30 days after treatment, the antitumour effect of {sup 225}Ac-DOTA-F3 (t{sub 1/2} 10 days) increased at later time-points. The difference in the fraction of necrotic cells after treatment with {sup 225}Ac-DOTA-F3 (43%) and with {sup 213}Bi-DTPA-F3 (36%) was not significant. Though histological analysis of kidney samples revealed acute tubular necrosis and tubular oedema in 10-30% of animals after treatment with {sup 225}Ac-DOTA-F3 or {sup 213}Bi-DTPA-F3, protein casts were negligible (2%), indicating only minor damage to the kidney. Therapy with both {sup 225}Ac-DOTA-F3 and {sup 213}Bi-DTPA-F3 increased survival of mice with peritoneal carcinomatosis. Mild renal toxicity of both

  3. Gef gene therapy enhances the therapeutic efficacy of cytotoxics in colon cancer cells.

    Science.gov (United States)

    Ortiz, Raúl; Prados, Jose; Melguizo, Consolación; Rama, Ana R; Alvarez, Pablo J; Rodríguez-Serrano, Fernando; Caba, Octavio; Boulaiz, Houria; Aranega, Antonia

    2012-10-01

    The potential use of gene therapy to improve the response of patients with advanced cancer is being intensively analyzed. We evaluated the cytotoxic impact of the gef gene, a suicide gene, which has a demonstrated antiproliferative activity in tumor cells, in colon carcinoma cells in order to improve the antitumour effect of chemotherapeutic drugs used as first line treatment in the management of advanced colon cancer. We found that the gef gene induced a marked decrease in cell viability (50% in 24h) in T-84 cells through cell death by apoptosis. Interestingly, when gef gene expression was combined with drugs of choice in the clinical treatment of colon cancer (5-fluorouracil, oxaliplatin and irinotecan), a strong synergistic effect was observed with approximately a 15-20% enhancement of the antiproliferative effect. Our data demonstrate, for the first time, that gef gene expression induces significant growth arrest in colon cancer cells and that it is able to enhance the effect of some cytotoxic drugs compared with a single therapeutic approach. These results indicate the potential therapeutic value of the gef gene in colon cancer combination therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Therapeutic efficacy of a hybrid mandibular advancement device in the management of obstructive sleep apnea assessed with acoustic reflection technique

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    S S Agarwal

    2015-01-01

    Full Text Available Obstructive sleep apnea (OSA is one of the most common forms of sleep-disordered breathing. Various treatment modalities include behavior modification therapy, nasal continuous positive airway pressure (CPAP, oral appliance therapy, and various surgical modalities. Oral appliances are noninvasive and recommended treatment modality for snoring, mild to moderate OSA cases and severe OSA cases when patient is not compliant to CPAP therapy and unwilling for surgery. Acoustic reflection technique (ART is a relatively new modality for three-dimensional assessment of airway caliber in various clinical situations. The accuracy and reproducibility of acoustic rhinometry and acoustic pharyngometry assessment are comparable to computerized tomography and magnetic resonance imaging. This case report highlights the therapeutic efficacy of an innovative customized acrylic hybrid mandibular advancement device in the management of polysomnography diagnosed OSA cases, and the treatment results were assessed by ART.

  5. Therapeutic efficacy of a mixture of ivermectin and closantel against gastrointestinal parasites in draft horses

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    M. K. Aldelami

    2009-01-01

    Full Text Available Examination of 19 fecal samples showed positive results for nematodes. It was classified as a single and mixed infestation 58.0% and 42.1% respectively. The percentages of infestation with Strongylus spp, Oxyuris equi and Parascaris equorum were 31.58%, 15.75%, 10.52% respectively. Administration of a single dose of mixture of ivermectin and closantel (0.05 ml/kg body weight revealed a significant reduction in average egg count in feces of the treated horses with both single and mixed infection. Efficacy of mixture of ivermectin and closantel for was 100% in removing eggs of the Parascaris equorm and Oxyuris equi and 99.42% for Strongylus spp at 14 days post-treatment. The preparation was also effective in removing larvae of Gastrophilus nasalis.

  6. Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve.

    Science.gov (United States)

    Celik, Ilhan; Sürücü, Oguzkan; Dietz, Carsten; Heymach, John V; Force, Jeremy; Höschele, Iris; Becker, Christian M; Folkman, Judah; Kisker, Oliver

    2005-12-01

    We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.

  7. Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis.

    Science.gov (United States)

    Arzi, Boaz; Clark, Kaitlin C; Sundaram, Ayswarya; Spriet, Mathieu; Verstraete, Frank J M; Walker, Naomi J; Loscar, Megan R; Fazel, Nasim; Murphy, William J; Vapniarsky, Natalia; Borjesson, Dori L

    2017-08-01

    Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8(lo) cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710-1722. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  8. Therapeutic Efficacy of Aldoxorubicin in an Intracranial Xenograft Mouse Model of Human Glioblastoma

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    Luis Marrero

    2014-10-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo, aldoxorubicin (Aldoxo, which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents—3/4 maximum tolerated dose (MTD], Doxo [6 mg/kg (3/4 MTD], or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67 and abundant intratumoral programmed cell death (cleaved caspase-3. Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.

  9. Therapeutic Efficacy of Aldoxorubicin in an Intracranial Xenograft Mouse Model of Human Glioblastoma12

    Science.gov (United States)

    Marrero, Luis; Wyczechowska, Dorota; Musto, Alberto E.; Wilk, Anna; Vashistha, Himanshu; Zapata, Adriana; Walker, Chelsey; Velasco-Gonzalez, Cruz; Parsons, Christopher; Wieland, Scott; Levitt, Daniel; Reiss, Krzysztof; Prakash, Om

    2014-01-01

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents—3/4 maximum tolerated dose (MTD)], Doxo [6 mg/kg (3/4 MTD)], or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM. PMID:25379024

  10. [Therapeutic efficacy during active phases of multiple sclerosis: gait analysis and comparison with the EDSS score].

    Science.gov (United States)

    Fauchard-Renard, C; Renard, J F; Miret, N; Hannequin, D; Mihout, B; Weber, J

    2001-07-01

    Fifteen patients experiencing a flare-up of multiple sclerosis were given 1 g methylprednosolone per day for 5 days. The EDSS score and gait analysis using spatio-temporal variables were recorded for these patients on days 0, 5 and 45. Both methods evidenced significant improvement but the significance was observed between day 0 and day 5 for the EDSS and between day 5 and 45 for gait speed and between day 0 and 45 for step rate. Gait speed was correlated with the pyramidal scale but not with the other functional scales of the EDSS. These results suggest that EDSS and spatio-temporal gait analysis are different tools for the assessment of therapeutic effect. Gait analysis can provide a precise quantitative assessment of the locomotor handicap as a function of the proposed treatment.

  11. Liposomal bortezomib nanoparticles via boronic ester prodrug formulation for improved therapeutic efficacy in vivo.

    Science.gov (United States)

    Ashley, Jonathan D; Stefanick, Jared F; Schroeder, Valerie A; Suckow, Mark A; Kiziltepe, Tanyel; Bilgicer, Basar

    2014-06-26

    In this study, we describe the development of liposomal bortezomib nanoparticles, which was accomplished by synthesizing bortezomib prodrugs with reversible boronic ester bonds and then incorporating the resulting prodrugs into the nanoparticles via surface conjugation. Initially, several prodrug candidates were screened based upon boronic ester stability using isobutylboronic acid as a model boronic acid compound. The two most stable candidates were then selected to create surface conjugated bortezomib prodrugs on the liposomes. Our strategy yielded stable liposomal bortezomib nanoparticles with a narrow size range of 100 nm and with high reproducibility. These liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity against multiple myeloma cell lines in vitro and remarkable tumor growth inhibition with reduced systemic toxicity compared to free bortezomib in vivo. Taken together, this study demonstrates the incorporation of bortezomib into liposomal nanoparticles via reversible boronic ester bond formation to enhance the therapeutic index for improved patient outcome.

  12. In vitro efficacy of Bryophyllum pinnatum leaf extracts as potent therapeutics.

    Science.gov (United States)

    Gupta, Suneel; Adak, Sunita; Rajak, Rajiv Chandra; Banerjee, Rintu

    2016-07-01

    Leaf extracts of Bryophyllum pinnatum (BPEs) are used in several countries. Contextually, evaluation of the therapeutic potential of these was carried out in this study to explore antioxidant and antityrosinase potential through different in vitro methods. The radical scavenging properties of BPEs were studied using various techniques, based on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) dot blot thin-layer chromatography (TLC) method, electron paramagnetic resonance (EPR) spectroscopy, metal chelation, β-carotene bleaching, inhibition of DNA breakage on agarose gel, and lipid peroxidation inhibition using liver and brain microsomes. EC50 values of the results reflected that aqueous-methanolic BPE was the most active one. Antibrowning potential of the fresh leaf extract showed an antityrosinase property, with EC50 values of enzymatic assay of tyrosinase inhibitory activity further advocating the findings.

  13. Therapeutic efficacy and safety of Paeoniae Radix Rubra formulae in relieving hyperbilirubinemia induced by viral hepatitis: A meta-analysis

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    Yinqiu eHuang

    2016-03-01

    Full Text Available Objective: Hyperbilirubinemia is one of the most devastating pathologies induced by various liver diseases. Formulae related to Paeoniae Radix Rubra (PRR at high doses have been applied to treat hyperbilirubinemia in traditional Chinese medicine. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of formulae relevant to high-dose PRR in patients suffering from hyperbilirubinemia induced by viral hepatitis.Methods: We performed a meta-analysis of randomized-controlled clinical trials to evaluate the efficacy and safety of formulae that apply a high dose of PRR for hyperbilirubinemia. Seven databases were searched until April 2015. All studies were included according to detailed criteria and assessed for methodological quality. The outcome measurements were recorded for further analysis using the Revman 5.2.11 software. Results: Fifteen articles involving 1323 patients with hyperbilirubinemia were included. Formulae with high-dose PRR might promote the efficacy of either a combined application ([OR: 3.98, 95%CI (2.91, 5.43]; P<0.01 or a single application ([OR: 4.00, 95%CI (1.50, 10.68]; P<0.01 for hyperbilirubinemia. The indices of TBIL, ALT and AST significantly decreased ([MD: -75.57, 95%CI (-94.88, -56.26], [MD: -26.54, 95%CI (-36.19, -16.88] and ([MD: -28.94, 95%CI (-46.26, -11.61]; P<0.01, respectively. In addition, formulae with high-dose PRR could enhance the treatment efficacy of hyperbilirubinemia triggered by hepatitis B ([OR: 2.98, 95% CI (1.75, 5.05]; P<0.01. Furthermore, the efficacy was enhanced with an increasing dosage of PRR. Two articles reported that no side effects occurred in clinical trials, and 3 studies noted that patients presented light digestive tract symptoms.Conclusion: Formulae relevant to high-dose PRR ameliorate hyperbilirubinemia and might constitute a promising therapeutic approach. For widespread acceptance by practitioners, more rigorously designed multicenter, double

  14. In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection.

    Science.gov (United States)

    Chen, Chen; Mangoni, Maria Luisa; Di, Y Peter

    2017-08-17

    Pseudomonas aeruginosa is an opportunistic and frequently drug-resistant pulmonary pathogen especially in cystic fibrosis sufferers. Recently, the frog skin-derived antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c were found to possess potent in vitro antipseudomonal activity. Here, they were first shown to preserve the barrier integrity of airway epithelial cells better than the human AMP LL-37. Furthermore, Esc(1-21)-1c was more efficacious than Esc(1-21) and LL-37 in protecting host from pulmonary bacterial infection after a single intra-tracheal instillation at a very low dosage of 0.1 mg/kg. The protection was evidenced by 2-log reduction of lung bacterial burden and was accompanied by less leukocytes recruitment and attenuated inflammatory response. In addition, the diastereomer was more efficient in reducing the systemic dissemination of bacterial cells. Importantly, in contrast to what reported for other AMPs, the peptide was administered at 2 hours after bacterial challenge to better reflect the real life infectious conditions. To the best of our knowledge, this is also the first study investigating the effect of AMPs on airway-epithelia associated genes upon administration to infected lungs. Overall, our data highly support advanced preclinical studies for the development of Esc(1-21)-1c as an efficacious therapeutic alternative against pulmonary P. aeruginosa infections.

  15. Therapeutic efficacy for hepatocellular carcinoma by boric acid-mediated boron neutron capture therapy in a rat model.

    Science.gov (United States)

    Lin, Sy-Yu; Lin, Chen-Jou; Liao, Jiunn-Wang; Peir, Jinn-Jer; Chen, Wei-Lin; Chi, Chin-Wen; Lin, Yung-Chang; Liu, Yu-Ming; Chou, Fong-In

    2013-11-01

    Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

  16. Histone deacetylase inhibitor pracinostat in doublet therapy: a unique strategy to improve therapeutic efficacy and to tackle herculean cancer chemoresistance.

    Science.gov (United States)

    Ganai, Shabir Ahmad

    2016-09-01

    Context Histone deacetylase inhibitors (HDACi) have shown promising results in neurodegeneration and cancer. Hydroxamate HDACi, including vorinostat, have shown encouraging results in haematological malignancies, but the poor pharmacokinetic of these inhibitors leads to insufficient tumour concentration limiting their application against solid malignancies. Objective This article deals with novel HDAC inhibitor pracinostat (SB939) and delineates its therapeutic role in solid and haematological malignancies. The article provides rigorous details about the underlying molecular mechanisms modulated by pracinostat to exert cytotoxic effect. The article further highlights the doublet therapy that may be used to tackle monotonous cancer chemoresistance. Methods Both old and the latest literature on pracinostat was retrieved from diverse sources, such as PubMed, Science Direct, Springer Link, general Google search using both pracinostat and SB939 keywords in various ways: after thorough evaluation the topic which can fulfil the current gap was chosen. Results Pracinostat shows potent anticancer activity against both solid and haematological malignancies compared to the FDA-approved drug vorinostat. This marvellous inhibitor has better physicochemical, pharmaceutical and pharmacokinetic properties than the defined inhibitor vorinostat. Pracinostat has  >100-fold more affinity towards HDACs compared to other zinc-dependent metalloenzymes and shows maximum efficacy when used in doublet therapy. Conclusion Pracinostat shows potent anticancer activity even against therapeutically challenging cancers when used in doublet therapy. However, the triplet combination studies of the defined inhibitor that may prove even more beneficial are still undone, emphasizing the desperate need of further research in the defined gap.

  17. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity.

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    Anne Kleijn

    Full Text Available The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.

  18. EVALUATION OF THE THERAPEUTIC EFFICACY OF HIGH-INTENSITY PULSED-PERIODIC LASER RADIATION (CLINICAL AND EXPERIMENTAL OBSERVATIONS

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    V. V. Sokolov

    2016-01-01

    Full Text Available From the experience of clinical observations, we have shown a high therapeutic effectiveness of the medical laser KULON-MED in: cosmetics, non-cancer inflammatory diseases of the gastrointestinal tract and cancer (cancer of the stomach and colon as at different wavelengths, and with different types of photosensitizers. In the area of anti-tumor photodynamic therapy (PDT, based on experimental studies, we have showed the high antitumor (sarcoma S‑37 effectiveness of the laser (with the inhibition of tumor growth of up to 100% for repetitively pulsed irradiation mode, and for mode fractionation doses laser radiation. In addition, significant differences are shown in the effectiveness of anticancer PDT methods in the application of high-intensity lasers, continuous and pulsed caused fundamental properties of laser radiation characteristics – time structure of the radiation pulses. Thus, for the first time we have shown that the time of high-intensity laser pulses structure significantly affects therapeutic efficacy laser system, and hence on the mechanisms of interaction of laser radiation with biological tissue.

  19. Association of ABCB1 gene polymorphisms and haplotypes with therapeutic efficacy of glucocorticoids in Chinese patients with immune thrombocytopenia.

    Science.gov (United States)

    Xuan, Min; Li, Huiyuan; Fu, Rongfeng; Yang, Yanhui; Zhang, Donglei; Zhang, Xian; Yang, Renchi

    2014-04-01

    Resistance to glucocorticoids (GCs) remains a tricky problem complicating the therapy of ITP. Recently, ATP binding cassette gene B1 gene (ABCB1) was reported to be correlated with susceptibility and therapeutic efficacy of autoimmune diseases through P-glycoprotein (Pgp). We investigated three single nucleotide polymorphisms (SNPs) of ABCB1 and their haplotypes by PCR-RFLP (restriction fragment length polymorphism) method in 471 ITP patients and 383 healthy controls, patients were further assigned into GCs-responsive and -non-responsive group according to the therapeutic effects of GCs. We observed a remarkable difference in genotypes of G2677T/A between GCs-responsive and non-responsive group, but not between patients and controls. A frequently expression of T/A allele within G2677T/A was recorded in GCs-responsive group. Furthermore, we found that some haplotypes (CGC, CTC/CAC, CTT/CAT, TGC, TGT, TTC/TAC and TTT/TAT, in the order of position 1236-2677-3435) were presented significantly differences between non-responsive and responsive group. No difference of C1236T and C3435T polymorphisms was observed between ITP and controls, and between the GCs-responsive and -non-responsive group. Our findings suggest that ABCB1 polymorphisms, as well as haplotypes derived from C1235T, G2677T/A and C3435T, are associated with inter-individual differences of GCs treatment in ITP.

  20. EFFICACY OF SOFT TISSUE APPLICATION, MANUALLY-THERAPEUTICAL TECHNIQUES FOR KNEE ARTHROKINEMATICS RECOVERY COMPLEX IN PATIENTS AFTER ARTHROSCOPIC MENISCECTOMY

    Directory of Open Access Journals (Sweden)

    Kostov Rostislav V

    2015-07-01

    Full Text Available Introduction: In this article we present the final effect of the application of complex soft tissue manually-treatment system for recovery of joint kinematics in patients with moderate and minimal protective period of rehabilitation after arthroscopic meniscectomy. Material and Methods: The study was conducted in 2005-2012 into three medical centers in Bulgaria: Blagoevgrad, Sofia and Pleven. The study included a total of 110 patients divided into three groups (Control and Experimental I and Experimental Group II who studied the effect of topical application of the manual therapeutic techniques compared to traditional rehabilitation methods applied. For testing the efficacy of a treatment approach in the three groups of patients, the results have processed by the method of variational analysis. Results: After analysis of results we find significantly more fully and without residual short violations recovery for all controlled parameters in patients who have implemented comprehensive manually-therapeutic treatment compared with control group patients. Conclusion: Application of adequate physiological and pedagogically grounded complex rehabilitation is required in patients after arthroscopic meniscectomy model with motor deficits in tractable routine rehabilitation. Observations allow us to offer a methodology for implementation in general practice rehabilitation in patients after meniscal ruptures treated by arthroscopic meniscectomy and motor deficits, intractable routine rehabilitation.

  1. Long Term Therapeutic Efficacy of a Soft Monobloc Mandibular Advancement Device in Adults with Obstructive Sleep Apnea

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    Fabiana Ballanti

    2015-01-01

    Full Text Available Aim. To evaluate the long term (48 months therapeutic efficacy of a soft monobloc mandibular advancement device in adult patients with mild or moderate obstructive sleep apnea. Methods. The study population comprised 28 patients (6 female and 22 male, mean age 52.2±6.8 years affected by obstructive sleep apnea. After a baseline medical and somnographic examination, a functional examination of the stomatognathic system, and a questionnaire focused on sleep-related qualities and a daytime somnolence, each patient received an individual device. Two follow-ups were made 6 months (T1 and 48 months (T2 after soft monobloc mandibular advancement device treatment had been initiated, and all initial examinations were repeated. Results. The statistical analysis showed a significant decrease in body mass index value between T1 and T2 (ρ = 0,012, an increase of Epworth sleepiness scale value between T1 and T2 (ρ = 0,012, and a significant improvement and decrease of apnea/hypopnea index between T0 and T1 (ρ = 0,010 and between T0 and T2 (ρ = 0,013. Conclusion. Treatment with the soft monobloc mandibular advancement device is a therapeutic solution with long term and stable effects (48 months for patients suffering from mild or moderate obstructive sleep apnea.

  2. Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Qi-Kui Chen; Zhong-Lin Yu; Shi-Zheng Yuan; Zhuo-Fu Wen; Ying-Qiang Zhong; Cu-Jun Li; Hui-Sheng Wu; Can-Rong Mai; Peng-Yan Xie; Yu-Min Lu

    2005-01-01

    AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC).METHODS: Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106patients in 1993-1995, and 122 patients in 2000-2002,they were assigned as the 1990s group (n = 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups.The short-term efficacy and safety of SASP 3 g per d were evaluated.RESULTS: Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4%and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P<0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P<0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P<0.05). Rough and granular mucosa (67.9%vs43.4%, P<0.05)and polyps (47.2% vs 32.8%, P<0.05)were identified in 1990s group more than in 2000s group.There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%,respectively. In 79 patients with clinical remission, 58.2%and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were

  3. Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

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    William A Prescott

    2014-01-01

    Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

  4. FPA-FTIR Microspectroscopy for Monitoring Chemotherapy Efficacy in Triple-Negative Breast Cancer

    Science.gov (United States)

    Zawlik, Izabela; Kaznowska, Ewa; Cebulski, Jozef; Kolodziej, Magdalena; Depciuch, Joanna; Vongsvivut, Jitraporn; Cholewa, Marian

    2016-11-01

    Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.

  5. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.

    Science.gov (United States)

    Gulati, Karan; Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M; Atkins, Gerald J; Losic, Dusan

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements.

  6. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    Science.gov (United States)

    Li, Wenchang; He, Bing; Dai, Wenbing; Zhang, Qiang; Liu, Yuling

    2014-06-01

    Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

  7. Therapeutic monitoring of pediatric renal transplant patients with conversion to generic cyclosporin.

    Science.gov (United States)

    Riva, Natalia; Guido, Paulo Caceres; Ibañez, Juan; Licciardone, Nieves; Rousseau, Marcela; Mato, Gabriel; Monteverde, Marta; Schaiquevich, Paula

    2014-08-01

    Cyclosporin is a calcineurin inhibitor widely used in renal transplant patients to prevent organ rejection. Several position papers have been published but no reports on the practical experience in pediatric patients undergoing conversion between cyclosporin innovator and generic products are available. To evaluate the pharmacokinetics and safety as part of therapeutic monitoring of cyclosporin in renal transplant pediatric patients who switch from the innovator to the generic formulation in Argentina. Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina. Stable pediatric renal transplant patients (6 months post-transplant) switched from the innovator to the generic formulation of cyclosporin microemulsion capsule. Cyclosporin pharmacokinetic parameters were obtained while taking the innovator and after starting with the generic formulation. Blood samples were drawn before and 1, 2, and 3 h after drug administration and subsequently quantified. Pharmacokinetic parameters were obtained by means of a Bayesian approach. Cyclosporin pharmacokinetic parameters (area under the curve, AUC; Blood concentration after 2 h, C2), adverse events and graft rejection. A total of 12 patients were included. Median (range) age and time post-transplant were 10.7 years (6.5-17.7) and 8.3 years (3.4-14.0), respectively. Two patients or their parents did not consent to the switch. Median (range) dose normalized cyclosporin AUC and C2 were 1.15 (mg*h/L)/mg/kg (0.72-3.0) and 265.5 (ng/ml)/mg/kg (120.8-725.7), respectively, on the innovator therapy and 1.05 (mg*h/L)/mg/kg (0.54-2.22) and 317.1 (ng/ml)/mg/kg (116.7-564.7) for the generic drug after the switch. The median (range) percentage of change in the AUC and C2 when switching between formulations were 16.7 % (0.7-56.7) and 13.1 % (3.7-68.6), respectively. No significant changes in serum creatinine levels were registered when comparing before and after substitution of products. Adverse events (number of events) recorded 5 months

  8. Immunoliposome co-delivery of bufalin and anti-CD40 antibody adjuvant induces synergetic therapeutic efficacy against melanoma

    Directory of Open Access Journals (Sweden)

    Li Y

    2014-12-01

    Full Text Available Ying Li,1,* Jiani Yuan,1,* Qian Yang,1 Wei Cao,1 Xuanxuan Zhou,1 Yanhua Xie,1 Honghai Tu,2 Ya Zhang,1 Siwang Wang1 1Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Institute for Drug and Instrument Control, Xinjiang Military Area Command, Urumqi, Xinjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL conjugated with anti-CD40 antibody (anti-CD40-BFL showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm3 versus 270 mm3, respectively; the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistribution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic

  9. Therapeutic efficacy of posaconazole against Candida glabrata in a murine model of vaginitis.

    Science.gov (United States)

    González, Gloria M; Elizondo, Mariana; Garza-González, Elvira; González, J Gerardo

    2011-03-01

    The frequency of mucosal infections caused by Candida glabrata has increased significantly. Candida glabrata infections are often resistant to many azole antifungal agents, especially fluconazole. The purpose of this study was to compare the efficacies of posaconazole (PSC) and fluconazole (FLC) in the treatment of experimental C. glabrata vaginitis caused by isolates with different FLC susceptibilities. A battery of 36 vaginal isolates of C. glabrata was tested against PSC and FLC to determine their in vitro susceptibilities. The 48-h geometric mean MICs for all isolates tested were 0.156 and 4.238 μg ml(-1) for PSC and FLC respectively. Two strains of C. glabrata for which FLC MICs were different were selected for in vivo study. The treatment regimens for the vaginal murine infection model were PSC or FLC at 10 or 20 mg kg(-1) of body weight/day and 20 mg kg(-1) twice a day. Regimens with PSC at 20 mg kg(-1) once or twice a day were effective in reducing the load of both the FLC-susceptible and -resistant isolates of C. glabrata. FLC at 20 mg kg(-1) twice a day was effective in reducing the load of both the isolates of C. glabrata. PSC displayed a more effective in vivo activity than FLC in the treatment of murine C. glabrata vaginitis. © 2009 Blackwell Verlag GmbH.

  10. Therapeutic efficacy of the combination of intratympanic methylprednisolone and oral steroid for idiopathic sudden deafness.

    Science.gov (United States)

    Gundogan, Onur; Pinar, Ercan; Imre, Abdulkadir; Ozturkcan, Sedat; Cokmez, Ozge; Yigiter, Ali Cihan

    2013-11-01

    The purpose of this study was to compare the efficacy of systemic steroid alone and combined with intratympanic methylprednisolone in the treatment of patients with idiopathic sudden sensorineural hearing loss. Prospective, randomized controlled trial. Settings Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey. Seventy-nine patients who met the inclusion criteria for idiopathic sudden sensorineural hearing loss were included in this study. Patients were randomly divided into 2 groups according to treatment: group A received combination therapy (intratympanic methylprednisolone + oral steroid) and group B received oral steroid alone. Of the 79 patients included, 6 patients missed the 1-month follow-up visit. Overall, 73 patients (37 combination group, 36 oral steroid group) who completed the 1-month follow-up and study intervention were included in the per-protocol analysis. Both the relationship between certain prognostic factors and the clinical outcome after treatment were analyzed. Combination therapy showed significant hearing improvement and speech discrimination scores compared with the use of systemic steroids alone (P < .05). In hearing outcomes in patients with severe hearing loss, combination therapy had statistically significant hearing improvement compared with oral steroid alone (P < .05). We recommend that combination therapy can be considered as initial treatment especially for patients with severe hearing loss.

  11. Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

    Science.gov (United States)

    Bentzley, Brandon S.; Jhou, Thomas C.; Aston-Jones, Gary

    2014-01-01

    Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments. PMID:25071176

  12. Therapeutic Efficacy of Misoprostol versus Ethacridine Lactate in Second Trimester Abortion – Randomised Controlled Study

    Directory of Open Access Journals (Sweden)

    Kruti Deliwala

    2013-02-01

    Full Text Available Background: Abortion is a major health and social issue in our country .Techniques for abortions are highly varied in different areas of country. Present study is to compare newer abortificient misoprostol versus traditionally used ethacridine lactate method. Objective: To observe the efficacy and safety of misoprostol as a second trimester abortificient and to compare it with ethacridine lactate. Methods: This is a prospective study of 100 women with 12 – 20 weeks of gestation. Inclusions were according to MTP Act. 400ug misoprostol was inserted vaginally followed by 200ug every 4 hourly in study group (n=50.150-200ml of ethacridine lactate was injected extraamniotically in control group (n=50.Latent phase, active phase and induction abortion interval was noted and compared Results: Average induction abortion interval was 12.24 hours in misoprostol as compared to 27.6 hours in ethacridine lactate (P value <0.01. The women undergoing D & E due to incomplete abortion was higher with ethacridine group 12( 24% as compared to misoprostol group 8 (14% (P <0.05. Conclusion: Misoprostol is faster, convenient, and safer than ethacridine lactate for 2nd trimester abortion. [Natl J of Med Res 2013; 3(1.000: 16-18

  13. Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms

    Science.gov (United States)

    Bhagwat, Neha; Koppikar, Priya; Keller, Matthew; Marubayashi, Sachie; Shank, Kaitlyn; Rampal, Raajit; Qi, Jun; Kleppe, Maria; Patel, Hardik J.; Shah, Smit K.; Taldone, Tony; Bradner, James E.; Chiosis, Gabriela

    2014-01-01

    The discovery of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to clinical development of Janus kinase (JAK) inhibitors for treatment of MPN. These inhibitors improve constitutional symptoms and splenomegaly but do not significantly reduce mutant allele burden in patients. We recently showed that chronic exposure to JAK inhibitors results in inhibitor persistence via JAK2 transactivation and persistent JAK–signal transducer and activator of transcription signaling. We performed genetic and pharmacologic studies to determine whether improved JAK2 inhibition would show increased efficacy in MPN models and primary samples. Jak2 deletion in vivo led to profound reduction in disease burden not seen with JAK inhibitors, and deletion of Jak2 following chronic ruxolitinib therapy markedly reduced mutant allele burden. This demonstrates that JAK2 remains an essential target in MPN cells that survive in the setting of chronic JAK inhibition. Combination therapy with the heat shock protein 90 (HSP90) inhibitor PU-H71 and ruxolitinib reduced total and phospho-JAK2 and achieved more potent inhibition of downstream signaling than ruxolitinib monotherapy. Combination treatment improved blood counts, spleen weights, and reduced bone marrow fibrosis compared with ruxolitinib alone. These data suggest alternate approaches that increase JAK2 targeting, including combination JAK/HSP90 inhibitor therapy, are warranted in the clinical setting. PMID:24470592

  14. Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Cies, Jeffrey J; Moore, Wayne S; Conley, Susan B; Shea, Paul; Enache, Adela; Chopra, Arun

    2017-01-01

    An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. By day 7 the patient (24.7 kg) had a positive fluid balance of 6925 mL (28% FO), and on days 7 into 8 developed acute kidney injury evidenced by an elevated serum creatinine of 0.68 mg/dL, an increase from the baseline of 0.28 mg/dL. On day 9, the patient was initiated on continuous renal replacement therapy (CRRT) and the doripenem dosing was changed to a continuous infusion of 2.5 mg/kg/hr (60 mg/kg/day). Approximately 12.5 hours after the start of the doripenem a serum concentration was obtained, which was 4.01 mg/L corresponding to a clearance of 10.5 mL/min/kg. The pediatric dosing and pharmacokinetic data available for doripenem suggest a clearance estimate of 4.4 to 4.8 mL/min/kg, and the adult clearance estimate is 2.4 to 3.78 mL/min/kg. The calculated clearance in our patient of 10.5 mL/min/kg is over double the highest clearance estimate in the pediatric literature. This case demonstrates that doripenem clearance is significantly increased with CRRT in comparison with the published pediatric and adult data. An appropriate pharmacodynamic outcome (time that free drug concentration > minimum inhibitory concentration) can be achieved by continuous infusion doripenem with concurrent therapeutic drug monitoring.

  15. Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres.

    Science.gov (United States)

    Falke, Lucas L; van Vuuren, Stefan H; Kazazi-Hyseni, Filis; Ramazani, Farshad; Nguyen, Tri Q; Veldhuis, Gert J; Maarseveen, Erik M; Zandstra, Jurjen; Zuidema, Johan; Duque, Luisa F; Steendam, Rob; Popa, Eliane R; Kok, Robbert Jan; Goldschmeding, Roel

    2015-02-01

    Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded microspheres under the kidney capsule of ureter-obstructed rats and assessed the local antifibrotic effects and systemic side effects of rapamycin. After 7 days, microsphere depots were easily identifiable under the kidney capsule. Both systemic and local rapamycin treatment reduced intrarenal mTOR activity, myofibroblast accumulation, expression of fibrotic genes, and T-lymphocyte infiltration. Upon local treatment, inhibition of mTOR activity and reduction of myofibroblast accumulation were limited to the immediate vicinity of the subcapsular pocket, while reduction of T-cell infiltration was widespread. In contrast to systemically administered rapamycin, local treatment did not induce off target effects such as weight loss. Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most prominent in close vicinity to the implanted microspheres.

  16. Therapeutic efficacy of neuromuscular electrical stimulation and electromyographic biofeedback on Alzheimer's disease patients with dysphagia.

    Science.gov (United States)

    Tang, Yi; Lin, Xiang; Lin, Xiao-Juan; Zheng, Wei; Zheng, Zhi-Kai; Lin, Zhao-Min; Chen, Jian-Hao

    2017-09-01

    To study the therapeutic effect of neuromuscular electrical stimulation and electromyographic biofeedback (EMG-biofeedback) therapy in improving swallowing function of Alzheimer's disease patients with dysphagia.A series of 103 Alzheimer's disease patients with dysphagia were divided into 2 groups, among which the control group (n = 50) received swallowing function training and the treatment group (n = 53) received neuromuscular electrical stimulation plus EMG-biofeedback therapy. The mini-mental state scale score was performed in all patients along the treatment period. Twelve weeks after the treatment, the swallowing function was assessed by the water swallow test. The nutritional status was evaluated by Mini Nutritional Assessment (MNA) as well as the levels of hemoglobin and serum albumin. The frequency and course of aspiration pneumonia were also recorded.No significant difference on mini-mental state scale score was noted between 2 groups. More improvement of swallowing function, better nutritional status, and less frequency and shorter course of aspiration pneumonia were presented in treatment group when compared with the control group.Neuromuscular electrical stimulation and EMG-biofeedback treatment can improve swallowing function in patients with Alzheimer's disease and significantly reduce the incidence of adverse outcomes. Thus, they should be promoted in clinical practice.

  17. Therapeutic efficacy by targeting correction of Notch1-induced aberrants in uveal tumors.

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    Xiaolin Huang

    Full Text Available There is a need for more effective treatments for uveal melanoma. The recombinant oncolytic adenovirus H101 replicates specifically in p53-depleted tumor cells, and has been approved for use by the Chinese State Food and Drug Administration. However, this treatment is associated with subsequent remission. Transfection of uveal melanoma cells with a small interfering RNA against Notch1 (siNotch1 effectively suppressed Notch1 expression, resulting in significant cell growth inhibition when combined with H101 treatment. Combined treatment with siNotch1 and H101 (H101-Notch1-siRNA greatly enhanced apoptosis and cell cycle arrest in vitro as compared to treatment with H101 or siNotch1 alone. For in vivo treatments, the combined treatment of siNotch1 and H101 showed remarkable tumor growth inhibition and prolonged mouse survival in the OCM1 xenograft model. We predict that Notch pathway deregulation could be a feature of uveal melanoma, and could be a therapeutic target, especially if p53 is concurrently targeted.

  18. The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of tabun poisoning in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Pavlikova, Ruzena; Misik, Jan; Caisberger, Filip; Bajgar, Jiri

    2010-03-01

    The influence of the combination of oximes on the reactivating and therapeutic efficacy of antidotal treament of acute tabun poisoning was evaluated. The ability of two combinations of oximes (HI-6 + obidoxime and HI-6 + K203) to reactivate tabun-inhibited acetylcholinesterase and reduce acute toxicity of tabun was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, obidoxime, K203) using in vivo methods. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is higher than the reactivating efficacy of the most effective individual oxime in blood and diaphragm and comparable with the reactivating effects of the most effective individual oxime in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in tabun-poisoned mice than the antidotal treatment involving individual oxime. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the newly developed oxime K203 is slightly more effective than commonly used obidoxime and both of them are markedly more effective than the oxime HI-6. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings beneficial effects for the potency of antidotal treatment to reactivate tabun-inhibited acetylcholinesterase in rats and to reduce acute toxicity of tabun in mice.

  19. Exercise Therapy for Management of Type 2 Diabetes Mellitus: Superior Efficacy of Activity Monitors over Pedometers

    Science.gov (United States)

    Umezono, Tomoya; Fukagawa, Masafumi

    2016-01-01

    We compared the efficacy of activity monitor (which displays exercise intensity and number of steps) versus that of pedometer in exercise therapy for patients with type 2 diabetes. The study subjects were divided into the activity monitor group (n = 92) and pedometer group (n = 95). The primary goal was improvement in hemoglobin A1c (HbA1c). The exercise target was set at 8,000 steps/day and 20 minutes of moderate-intensity exercise (≥3.5 metabolic equivalents). The activity monitor is equipped with a triple-axis accelerometer sensor capable of measuring medium-intensity walking duration, number of steps, walking distance, calorie consumption, and total calorie consumption. The pedometer counts the number of steps. Blood samples for laboratory tests were obtained during the visits. The first examination was conducted at the start of the study and repeated at 2 and 6 months. A significant difference in the decrease in HbA1c level was observed between the two groups at 2 months. The results suggest that the use of activity level monitor that displays information on exercise intensity, in addition to the number of steps, is useful in exercise therapy as it enhances the concept of exercise therapy and promotes lowering of HbA1c in diabetic patients. PMID:27761471

  20. Exercise Therapy for Management of Type 2 Diabetes Mellitus: Superior Efficacy of Activity Monitors over Pedometers

    Directory of Open Access Journals (Sweden)

    Masaaki Miyauchi

    2016-01-01

    Full Text Available We compared the efficacy of activity monitor (which displays exercise intensity and number of steps versus that of pedometer in exercise therapy for patients with type 2 diabetes. The study subjects were divided into the activity monitor group (n=92 and pedometer group (n=95. The primary goal was improvement in hemoglobin A1c (HbA1c. The exercise target was set at 8,000 steps/day and 20 minutes of moderate-intensity exercise (≥3.5 metabolic equivalents. The activity monitor is equipped with a triple-axis accelerometer sensor capable of measuring medium-intensity walking duration, number of steps, walking distance, calorie consumption, and total calorie consumption. The pedometer counts the number of steps. Blood samples for laboratory tests were obtained during the visits. The first examination was conducted at the start of the study and repeated at 2 and 6 months. A significant difference in the decrease in HbA1c level was observed between the two groups at 2 months. The results suggest that the use of activity level monitor that displays information on exercise intensity, in addition to the number of steps, is useful in exercise therapy as it enhances the concept of exercise therapy and promotes lowering of HbA1c in diabetic patients.

  1. Therapeutic efficacy of charcoal hemoperfusion in patients with acute severe dichlorvos poisoning

    Institute of Scientific and Technical Information of China (English)

    AiPENG; Fan-qingMENG; Lan-fangSUN; Zhan-shengJI; Yu-huiLI

    2004-01-01

    AIM: To assess the efficacy of hemoperfusion (HP) in the treatment of the patients with acute severe dichlorvos(DDVP) poisoning. METHODS: One hundred and eight patients with acute severe DDVP poisoning in the two teaching hospitals were enrolled. Sixty-seven patients were treated with HP (HP group) and forty-one patients accepted traditional treatment only as the control. Serum concentration of DDVP was determined by gas chromatography. RESULTS: The duration of coma, impaired consciousness, ICU stay, and mechanical ventilation was significantly shorter in the HP group than that in the control. The cumulative dosages (mg) of atropine required either in the first 24 h on admission (442±436 vs 899±485 in the control, P<0.01) or within the hospital (568±574vs 1228±982 in the control, P<0.01) were markedly reduced in the HP patients. The lower incidence of mechanical ventilation required (13.4 % vs 36.6 % P<0.01), respiratory muscular paralysis (4.5 % vs 17.1%, P<0.05) and the lower mortality of death (7.5 % vs 34.1%, P<0.01) were observed in the HP group. HP could accelerate the recovery of suppressed cholinesterase activity. After the procedure, the DDVP level was decreased from (11±4) to(7±3) mg/L in parallel with a decline in APACHE II Score or dopamine dose and a rise in Glasgow Coma Scale(P<0.05). In addition, the mean values of peak clearance and reduction rate were (87±17) mL/min and 44 %±11%,respectively. CONCLUSION: The rapid fall in blood DDVP level and the dramatic clinical response suggest that HP is effective in the treatment of acute severe DDVP poisoning.

  2. Alendronate. A review of its pharmacological properties and therapeutic efficacy in postmenopausal osteoporosis.

    Science.gov (United States)

    Jeal, W; Barradell, L B; McTavish, D

    1997-03-01

    Alendronate is an aminobisphosphonate which appears to attenuate, rather than completely inhibiting bone turnover, by suppressing the activity of osteoclasts. Clinical trials have established that 10 mg/day orally administered alendronate is the optimum dosage. Despite its poor bioavailability after oral administration, alendronate is highly effective at preventing bone loss associated with the absence of endogenous estrogen. A sustained increase in bone mass was observed during alendronate therapy without accelerated loss after withdrawal of the drug. Increased bone mass was associated with a reduction in the risk and rate of occurrence of vertebral fractures. A recent study demonstrated a 47% reduction in the risk of developing new radiographic vertebral fractures over 3 years in women with low bone mass and pre-existing vertebral fractures. There have been few direct comparisons in clinical trials. However, when compared with calcium or low dosages of salmon calcitonin (salcatonin) therapy in women with postmenopausal osteoporosis, alendronate induced a sustained increase in bone mass during therapy that was not seen with the comparator. In clinical trials alendronate was generally well tolerated when taken as recommended. Adverse events tended to be transient and usually associated with the upper gastrointestinal tract; the most common events included abdominal pain, nausea, dyspepsia, constipation and diarrhoea, which are also common with other bisphosphonates. Of potential concern are the small number of reports of patients developing oesophageal ulceration; however, this adverse event was attributed to noncompliance with the manufacturer's recommendations for administration of the drug. In addition, alendronate has not been associated with osteomalacia. Studies are still required to establish the long term efficacy of alendronate, particularly with regard to other available therapies. Although estrogen replacement therapy is generally considered the

  3. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia

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    Bacha Ketema

    2011-03-01

    Full Text Available Abstract Background Chloroquine is an anti-malarial drug being used to treat Plasmodium vivax malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against P. vivax strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR of South Ethiopia Results Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR. However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients, day 14 (six patients, and day 21 (one patient. The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/μl was higher than day of recurrence (372.37/μl. Parasite reduction ratio (PRR of treatment failure cases was 12.6/μl. Conclusion This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217] as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant P. vivax (CRPv strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.

  4. Therapeutic efficacy of small doses of colchicine combined with glucocorticoid for acute gouty arthritis

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    Ying LIU

    2015-10-01

    Full Text Available Objective To observe the clinical effect of small dose of colchicine combined with glucocorticoid for acute gouty arthritis. Methods Ninety-two patients with acute gouty arthritis were equally and randomly divided into small doses of colchicine combined with dexamethasone treatment group (treatment group and conventional large dose colchicine treatment group (control group between January 2009 and December 2013. The articular lesion scoring and clinical efficacy evaluation were performed at 3, 6, 12, 24, 48, and 72h after treatment. Erythrocyte sedimentation rate (ESR, white blood cells, hepatorenal function and glomerular filtration rate (GFR were determined before and 72h after treatment respectively. The gastrointestinal adverse events and recurrence rate were observed within one month after treatment. Results The articular lesion scores were significantly decreased at 6, 12, 48, and 72h after treatment in treatment group compared with control group (P0.05. Serum uric acid, glutamic-pyruvic transaminase in serum (SGPT, and GFR did not show any change before and 72h after the treatment, and there was also no significant difference between groups (P>0.05. The incidence of gastrointestinal adverse events were obviously higher in control group (76.1% compared with that of the treatment group (P<0.05, and the differences was statistically significant. There was no statistical difference in recurrence rate between the control group and treatment group after a follow-up of one month. Conclusions Compared with conventional large dose colchicine, small dose of colchicine combined with dexamethasone can more rapidly and effectively control acute gouty arthritis, with good tolerability and safety, thus being worthy of popularization clinically. DOI: 10.11855/j.issn.0577-7402.2015.08.10

  5. Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with {sup 64}Cu-DOTA-trastuzumab

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Gang; Cao, Qizhen; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Li, Zibo [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Keck School of Medicine, USC Molecular Imaging Center, Department of Radiology, Los Angeles, CA (United States)

    2009-09-15

    17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat-shock protein 90 (Hsp90) inhibitor, has been intensively investigated for cancer therapy and is undergoing clinical trials. Human epidermal growth factor receptor 2 (HER-2) is one of the client proteins of Hsp90 and its expression is decreased upon 17-DMAG treatment. In this study, we aimed to noninvasively monitor the HER-2 response to 17-DMAG treatment in xenografted mice. The sensitivity of human ovarian cancer SKOV-3 cells to 17-DMAG in vitro was measured by MTT assay. HER-2 expression in SKOV-3 cells was determined by flow cytometry. Nude mice bearing SKOV-3 tumors were treated with 17-DMAG and the therapeutic efficacy was evaluated by tumor size measurement. Both treated and control mice were imaged with microPET using {sup 64}Cu-DOTA-trastuzumab and {sup 18}F-FDG. Biodistribution studies and immunofluorescence staining were performed to validate the microPET results. SKOV-3 cells are sensitive to 17-DMAG treatment, in a dose-dependent manner, with an IC{sub 50} value of 24.72 nM after 72 h incubation. The tumor growth curve supported the inhibition effect of 17-DMAG on SKOV-3 tumors. Quantitative microPET imaging showed that {sup 64}Cu-DOTA-trastuzumab had prominent tumor accumulation in untreated SKOV-3 tumors, which was significantly reduced in 17-DMAG-treated tumors. There was no uptake difference detected by FDG PET. Immunofluorescence staining confirmed the significant reduction in tumor HER-2 level upon 17-DMAG treatment. The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using {sup 64}Cu-DOTA-trastuzumab. This approach may be valuable in monitoring the therapeutic response in HER-2-positive cancer patients under 17-DMAG treatment. (orig.)

  6. Design of dendrimer-based drug delivery nanodevices with enhanced therapeutic efficacies

    Science.gov (United States)

    Kannan, Rangaramanujam

    2007-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, `peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. They have significant potential compared to liposomes and nanoparticles, because of the reduced macrophage update, increased cellular transport, and the ability to modulate the local environment through functional groups. We are developing nanodevices based on dendritic systems for drug delivery, that contain a high drug payload, ligands, and imaging agents, resulting in `smart' drug delivery devices that can target, deliver, and signal. In collaboration with the Children's Hospital of Michigan, Karmanos Cancer Institute, and College of Pharmacy, we are testing the in vitro and in vivo response of these nanodevices, by adapting the chemistry for specific clinical applications such as asthma and cancer. These materials are characterized by UV/Vis spectroscopy, flow cytometry, fluorescence/confocal microscopy, and appropriate animal models. Our results suggest that: (1) We can prepare drug-dendrimer conjugates with drug payloads of greater than 50%, for a variety of drugs; (2) The dendritic polymers are capable of transporting and delivering drugs into cells faster than free drugs, with superior therapeutic efficiency. This can be modulated by the surface functionality of the dendrimer; (3) For chemotherapy drugs, the conjugates are a factor of 6-20 times more effective even in drug-resistant cell lines; (4) For corticosteroidal drugs, the dendritic polymers provide higher drug residence times in the lung, allowing for passive targeting. The ability of the drug-dendrimer-ligand conjugates to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

  7. Ultrasound-mediated oncolytic virus delivery and uptake for increased therapeutic efficacy: state of art

    Directory of Open Access Journals (Sweden)

    Nande R

    2015-11-01

    Full Text Available Rounak Nande,1 Candace M Howard,2 Pier Paolo Claudio,3,4 1Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV, 2Department of Radiology, University of Mississippi Medical Center, Jackson, MS, 3Department of BioMolecular Sciences and National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS, 4Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA Abstract: The field of ultrasound (US has changed significantly from medical imaging and diagnosis to treatment strategies. US contrast agents or microbubbles (MB are currently being used as potential carriers for chemodrugs, small molecules, nucleic acids, small interfering ribonucleic acid, proteins, adenoviruses, and oncolytic viruses. Oncolytic viruses can selectively replicate within and destroy a cancer cell, thus making them a powerful therapeutic in treating late-stage or metastatic cancer. These viruses have been shown to have robust activity in clinical trials when injected directly into tumor nodules. However limitations in oncolytic virus’ effectiveness and its delivery approach have warranted exploration of ultrasound-mediated delivery. Gene therapy bearing adenoviruses or oncolytic viruses can be coupled with MBs and injected intravenously. Following application of US energy to the target region, the MBs cavitate, and the resulting shock wave enhances drug, gene, or adenovirus uptake. Though the underlying mechanism is yet to be fully understood, there is evidence to suggest that mechanical pore formation of cellular membranes allows for the temporary uptake of drugs. This delivery method circumvents the limitations due to stimulation of the immune system that prevented intravenous administration of viruses. This review provides insight into this intriguing new frontier on the delivery of oncolytic viruses to tumor sites.Keywords: microbubbles, ultrasound

  8. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats.

    Science.gov (United States)

    Arzi, Boaz; Mills-Ko, Emily; Verstraete, Frank J M; Kol, Amir; Walker, Naomi J; Badgley, Megan R; Fazel, Nasim; Murphy, William J; Vapniarsky, Natalia; Borjesson, Dori L

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n=3) or substantial clinical improvement (n=2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6-24 months). In this study, cats with 15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings demonstrate that this therapy resulted in complete clinical and histological resolution or reduction in clinical disease

  9. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

    Science.gov (United States)

    Mills-Ko, Emily; Verstraete, Frank J.M.; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; Murphy, William J.; Vapniarsky, Natalia; Borjesson, Dori L.

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings demonstrate that this therapy resulted in complete clinical and histological resolution or

  10. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease.

    Science.gov (United States)

    Danielyan, Lusine; Schäfer, Richard; von Ameln-Mayerhofer, Andreas; Bernhard, Felix; Verleysdonk, Stephan; Buadze, Marine; Lourhmati, Ali; Klopfer, Tim; Schaumann, Felix; Schmid, Barbara; Koehle, Christoph; Proksch, Barbara; Weissert, Robert; Reichardt, Holger M; van den Brandt, Jens; Buniatian, Gayane H; Schwab, Matthias; Gleiter, Christoph H; Frey, William H

    2011-02-01

    Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10⁶ MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine, 5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40-110 days after INA of 1 × 10⁶ cells. MSC-INA decreased the concentrations of inflammatory cytokines-interleukin-1β (IL-1β), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-in the lesioned side to their

  11. Self-Assembled ROS-Sensitive Polymer-Peptide Therapeutics Incorporating Built-in Reporters for Evaluation of Treatment Efficacy.

    Science.gov (United States)

    Qiao, Zeng-Ying; Zhao, Wen-Jing; Cong, Yong; Zhang, Di; Hu, Zhiyuan; Duan, Zhong-Yu; Wang, Hao

    2016-05-09

    One of the major challenges in current cancer therapy is to maximize therapeutic effect and evaluate tumor progression under the scheduled treatment protocol. To address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated amphiphilic poly(β-thioester)s copolymers (H-P-K) composed of reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene glycol (PEG) side chains. H-P-K could self-assemble into micelle-like nanoparticles by hydrophobic interaction with copolymer backbones as cores and PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably improved cellular internalization and accumulation of therapeutic KLAK in cells. Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly enhanced up to ∼400 times, suggesting the effectiveness of the nanoscaled polymer-peptide conjugation as biopharmaceuticals. The higher antitumor activity of nanoparticles was attributed to the efficient disruption of mitochondrial membranes and subsequent excessive ROS production in cells. To realize the ROS monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built-in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around mitochondria stimulated the swelling of nanoparticles and subsequent release of SQ, which formed H-aggregates and significantly increased the photoacoustic (PA) signal. We believed that this self-assembled polymer-peptide nanotherapeutics incorporating built-in reporters has great potential for high antitumor performance and in situ treatment evaluation.

  12. Cross-Country Skiing as a Self-Efficacy Intervention with an Adolescent Female: An Innovative Application of Bandura's Theory to Therapeutic Recreation.

    Science.gov (United States)

    Ferguson, Daniel D.; Jones, Karna

    2001-01-01

    Used Bandura's theory of self-efficacy as a basis for designing a therapeutic recreation intervention (cross-country skiing) for an adolescent girl with severe depression and oppositional defiant disorder in a long-term residential treatment facility. The intervention facilitated increased self- confidence and helped her discover positive ways to…

  13. Therapeutic efficacy of tumor-derived heat shock protein 70 immunotherapy combining interleukin-2 on tumor-bearing mice

    Institute of Scientific and Technical Information of China (English)

    傅庆国; 孟凡东; 沈晓东; 郭仁宣

    2003-01-01

    Objective To investigate the therapeutic efficacy of compound immunotherapy of tumor-derived heat shock protein 70 (HSP70) and interleukin-2 (IL-2) on tumor-bearing mice, and to provide reference for translating this strategy to human cancer. Methods Cell culture, techniques for protein extraction and purification, SDS-PAGE, Wes tern blot and capillary electrophoresis for HSP70 detection and purity analysis, and animal experiments were used. Mice were treated with HSP70 5 or 10 μg and IL-2 50 kU, 100 kU or 2 kU (maintaining dosage) at pre viously designated intervals. Results Both the mono-administration of either HSP70 or IL-2 and the compound immunoth erapy of HSP70 and IL-2 obviously inhibited the growth of the implanted tumor and prolonged the life span of the mice to different extents. However, long periods of tumor-free suvival (over 90 days) were demonstrated only in HSP70 10 μg group, HSP70 10 μg-IL-2 50 kU group, and HSP70 10 μg-IL-2 100 kU group (4 0%, 40%, 60% respectively). On the other hand, none of the mice in the rest gr oups achieved long-term survival. Statistical significance was apparent in com parison with the groups without long period survival (P<0.025-0.05). Conclusion Our research revealed that tumor-derived HSP70 immunotherapy was much more effective than IL-2 alone. And in compound immunotherapy, HSP70 was the main factor in delaying or eradicating the tumors. The proper combination of HSP70 and IL-2 (10 μg HSP70 and 100 kU IL-2 in this experimental mouse model) clea rly enhanced the immunotherapy efficacy which indicated that the specific immuno therapy as a main part of tumor immunotherapy assisted by cytokine immunotherapy would be a promising strategy in cancer treatment.

  14. Cell therapy: a safe and efficacious therapeutic treatment for Alzheimer's disease in APP+PS1 mice.

    Science.gov (United States)

    Nabar, Neel R; Yuan, Fang; Lin, Xiaoyang; Wang, Li; Bai, Ge; Mayl, Jonathan; Li, Yaqiong; Zhou, Shu-Feng; Wang, Jinhuan; Cai, Jianfeng; Cao, Chuanhai

    2012-01-01

    Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2 × Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP + PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future.

  15. Cell therapy: a safe and efficacious therapeutic treatment for Alzheimer's disease in APP+PS1 mice.

    Directory of Open Access Journals (Sweden)

    Neel R Nabar

    Full Text Available Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD. In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2 × Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP + PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future.

  16. iNKT/CD1d-antitumor immunotherapy significantly increases the efficacy of therapeutic CpG/peptide-based cancer vaccine.

    Science.gov (United States)

    Corgnac, Stéphanie; Perret, Rachel; Zhang, Lianjun; Mach, Jean-Pierre; Romero, Pedro; Donda, Alena

    2014-01-01

    Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells. Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin. The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in

  17. Therapeutic Efficacy of Fuzheng-Huayu Tablet Based Traditional Chinese Medicine Syndrome Differentiation on Hepatitis-B-Caused Cirrhosis: A Multicenter Double-Blind Randomized Controlled Trail

    Directory of Open Access Journals (Sweden)

    Ya-Nan Song

    2013-01-01

    Full Text Available Aim. To evaluate and predict the therapeutic efficacy of Fuzheng-Huayu tablet (FZHY based traditional Chinese Medicine (TCM syndrome differentiation or TCM symptoms on chronic hepatitis B caused cirrhosis (HBC. Methods. The trial was designed according to CONSORT statement. It was a multi-center, double-blind, randomized, placebo-controlled trail. Several clinical parameters, Child-Pugh classification and TCM symptoms were detected and evaluated. The FZHY efficacy was predicted by an established Bayes forecasting method following the Bayes classification model. Results. The levels of HA and TCM syndrome score in FZHY group were significantly decreased (P<0.05 compared to placebo group, respectively. The efficacy of FZHY on TCM syndrome score in HBC patients with some TCM syndromes was better. In TCM syndrome score evaluation, there were 53 effective and 22 invalid in FZHY group. TCM symptoms predicted FZHY efficacy on HBC were close to Child-Pugh score prediction. Conclusion. FZHY decreases the levels of HA and TCM syndrome scores, improves the life quality of HBC patients. Moreover, there were different therapeutic efficacies among different TCM syndromes, indicating that accurate TCM syndrome differentiation might guide the better TCM treatment. Furthermore, the FZHY efficacy was able to predict by Bayes forecasting method through the alteration of TCM symptoms.

  18. Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters.

    Science.gov (United States)

    Nakano, K; Todo, T; Chijiiwa, K; Tanaka, M

    2001-04-01

    Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.

  19. Therapeutic Efficacy Observation on‘Setting F ire on the Mountain’ Manipulation by Lu Shou-yan for Cervical Radiculopathy

    Institute of Scientific and Technical Information of China (English)

    Sun Yi-jun; Wu Yao-chi; Zhang Jun-feng; Li Yan; Wang Ying

    2014-01-01

    Objective:To observe the clinical effect of‘setting fire on the mountain’ manipulation by Lu Shou-yan for cervical radiculopathy as well as the infrared thermographic changes of the cervical area before and after treatment. Methods:A total of 120 eligible cases with cervical radiculopathy were randomly allocated into an observation group and a control group, 60 in each group. Cases in the observation group were treated with Lu Shou-yan’s ‘setting fire on the mountain’ manipulation, whereas cases in the control group were treated with even reinforcing-reducing manipulation. After two courses of treatment, the infrared thermographic changes and overall therapeutic efficacies in the two groups were compared. Results: The recovery rate and total effective rate in the observation group were 68.3%and 98.3%respectively, versus 28.3%and 81.7%in the control group, showing statistical differences in recovery rate and total effective rate (both P Conclusion:‘Setting fire on the mountain’ manipulation by Lu Shou-yan is better than even reinforcing-reducing manipulation for cervical radiculopathy.

  20. Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide

    Directory of Open Access Journals (Sweden)

    Monir Moradzadeh Khiavi

    2015-06-01

    Full Text Available Purpose: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. Methods: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. Results: No statistically significant difference was found in the mean weight of five groups (p>0.05. No significant relationship was found between groups and mortality rate (P = 0. 39. In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001. The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001. Conclusion: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate.

  1. The Bench-to-Bedside Story of IL-17 and the Therapeutic Efficacy of its Targeting in Spondyloarthritis.

    Science.gov (United States)

    Smith, Judith A

    2016-06-01

    TNF-blocking biologics have revolutionized the care of patients with spondyloarthritis, a group of clinically overlapping conditions that includes ankylosing spondylitis and psoriatic arthritis. However, incomplete response rates speak to the need for alternative therapeutic approaches. Over the last decade, animal models, genetics, and translational studies have implicated the excessive production of a pro-inflammatory cytokine interleukin-17 (IL-17) along with another IL-17-promoting cytokine IL-23 in the pathogenesis of spondyloarthritis. Genome-wide studies identified disease associations with multiple genes regulating IL-23/IL-17 immune pathway activity. Direct examination of the patient blood and tissues revealed excessive IL-17 and IL-23 production by diverse cell types. Murine models both underscored the sufficiency of excess IL-23 in driving disease phenotype and predicted utility in IL-23/IL-17 pathway blockade. However, the clinical efficacy of agents such as secukinumab and ustekinumab, which block IL-17 and IL-23/IL-12 respectively, provided exciting proof of concept.

  2. Inhibition of TROY promotes OPC differentiation and increases therapeutic efficacy of OPC graft for spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Sun Liang; Feng Xiaoling; Duan Yongshun; Zhang Yafang; Wu Shuliang; Liu Shengliang; Sun Qi; Li Zhuying; Xu Fengyan; Hou Chunmei; Harada Toshihide; Chu Ming; Xu Kun

    2015-01-01

    Objective:To observe the regulatory effects of TROY on neural myelination in central nervous system ( CNS ) and remyelination in response to spinal cord injury ( SCI ) by oligodendrocyte precursor cell ( OPC) . Results:TROY expression was detected by RT-PCR and Western blotting in OPCs as well as in differen-tiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte mat-uration. Furthermore, treatment of co-cultures of DRG neurons and OPCs with TROY inhibitors promotes myelina-tion and myelin sheath-like structures. Mechanically, protein kinase C ( PKC) signaling is involved in the regula-tion of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notably enhanced remyelination as well as augmented recovery of motor function and nervous conduction in rats with SCI. Conclusions:Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.

  3. Therapeutic efficacy of Cernilton in benign prostatic hyperplasia patients with histological prostatitis after transurethral resection of the prostate

    Science.gov (United States)

    Qian, Xiaoqiang; Kong, Xiangjie; Qian, Yu; Xu, Ding; Liu, Hailong; Zhu, Yunkai; Guan, Wenbing; Zheng, Junhua; Wang, Zhong; Qi, Jun

    2015-01-01

    Objective: This study was to prospectively evaluate the therapeutic efficacy of Cernilton in benign prostatic hyperplasia (BPH) patients with histological prostatitis after transurethral resection of the prostate (TURP). Materials and methods: One hundred patients with histological prostatitis were recruited from January 2007 to January 2013. All patients were divided into groups A (mild), B (moderate), and C (severe) based on symptom severity, and then randomly subgrouped into Cernilton group and control group. Patients in Cernilton group were treated with Cernilton for 3 months after TURP, while patients in control group received placebo. A series of patient indicators were evaluated before, perioperatively (peri), and after TURP. Results: The assessed indicators remained unchanged peri-TURP as compared to those before surgery. 6 months after TURP, indicators remained stable in group A, and significant differences were observed in the International Index of Erectile Function-5 (IIEF-5) in group B and in the storage symptom score (Ss), quality of life (QoL) and IEFF-5 in group C. In addition, there were significant differences in Ss, QoL and IEFF-5 between Cernilton group and control group. Conclusion: In BPH patients with histological prostatitis after TURP, Cernilton can improve the lower urinary tract symptoms and sexual dysfunction depending on the grade of prostatitis. PMID:26379934

  4. Therapeutic efficacy of Cernilton in benign prostatic hyperplasia patients with histological prostatitis after transurethral resection of the prostate.

    Science.gov (United States)

    Qian, Xiaoqiang; Kong, Xiangjie; Qian, Yu; Xu, Ding; Liu, Hailong; Zhu, Yunkai; Guan, Wenbing; Zheng, Junhua; Wang, Zhong; Qi, Jun

    2015-01-01

    This study was to prospectively evaluate the therapeutic efficacy of Cernilton in benign prostatic hyperplasia (BPH) patients with histological prostatitis after transurethral resection of the prostate (TURP). One hundred patients with histological prostatitis were recruited from January 2007 to January 2013. All patients were divided into groups A (mild), B (moderate), and C (severe) based on symptom severity, and then randomly subgrouped into Cernilton group and control group. Patients in Cernilton group were treated with Cernilton for 3 months after TURP, while patients in control group received placebo. A series of patient indicators were evaluated before, perioperatively (peri), and after TURP. The assessed indicators remained unchanged peri-TURP as compared to those before surgery. 6 months after TURP, indicators remained stable in group A, and significant differences were observed in the International Index of Erectile Function-5 (IIEF-5) in group B and in the storage symptom score (Ss), quality of life (QoL) and IEFF-5 in group C. In addition, there were significant differences in Ss, QoL and IEFF-5 between Cernilton group and control group. In BPH patients with histological prostatitis after TURP, Cernilton can improve the lower urinary tract symptoms and sexual dysfunction depending on the grade of prostatitis.

  5. PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic efficacy of EtNBS-PDT in vitro

    Science.gov (United States)

    Hung, Hsin-I; Klein, Oliver J.; Peterson, Sam W.; Rokosh, Sarah R.; Osseiran, Sam; Nowell, Nicholas H.; Evans, Conor L.

    2016-01-01

    Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce “dark toxicity” through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule’s cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions. PMID:27686626

  6. Development of an online biosensor for in situ monitoring of chlorine dioxide gas disinfection efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Del Busto-Ramos, M.; Budzik, M.; Corvalan, C.; Morgan, M.; Nivens, D.; Applegate, B. [Purdue Univ., West Lafayette, IN (United States). Dept. of Food Science; Turco, R. [Purdue Univ., West Lafayette, IN (United States). Dept. of Agronomy

    2008-03-15

    A prototype bioluminescence-based biosensor was designed and constructed to evaluate the antimicrobial efficacy of chlorine dioxide (ClO{sub 2}) gas under various treatment conditions. The biosensor consisted of a bioluminescent bioreporter (Pseudomonas fluorescens 5RL), an optical transducer (photomultiplier tube), and a light-tight chamber housing, the bioreporter and the transducer. The bioluminescent recombinant P. fluorescens 5RL in the biosensor allowed for online monitoring of bioluminescence during ClO{sub 2} gas disinfection. Experiments were performed to evaluate the effects of the two key physical parameters associated with ClO{sub 2} disinfection: relative humidity (40, 60, 80%) and ClO{sub 2} gas concentration (0.5, 1.0, 1.6, 2.1 mg/l) on the bioreporter. Results showed that increasing concentrations of ClO{sub 2} gas corresponded to a faster decrease in luminescence. The rates of luminescence decrease from P. fluorescens 5RL, and the log reduction time (LRT, time required to obtain 1-log reduction in luminescence) were calculated for each treatment tested. The LRT values of luminescence were 103, 78, 53, and 35 s for 0.5, 1.0, 1.6, and 2.1 mg/l of ClO{sub 2} gas treatment, respectively, at 78% relative humidity. The gas concentration which caused a tenfold change in LRT (z value) for luminescence of P. fluorescens 5RL was 3.4 mg/l of ClO{sub 2}. The prototype biosensor showed potential for many applications, such as monitoring real-time microbial inactivation and understanding parameters that influence the efficacy of gaseous decontamination procedures. (orig.)

  7. Efficacy of intradermal mesotherapy in cellulite reduction - Conventional and high-frequency ultrasound monitoring results.

    Science.gov (United States)

    Sylwia, Malinowska; Krzysztof, Mlosek Robert

    2017-10-01

    Cellulite affects the majority of women and is an unacceptable cosmetic defect. Therefore, effective methods for cellulite reduction are being sought. Intradermal mesotherapy is one of such methods. The aim of the study was to assess the efficacy of intradermal mesotherapy in cellulite reduction, using conventional and high-frequency ultrasound. Twenty-one women with cellulite underwent a series of intradermal mesotherapy procedures. The following parameters were assessed: thickness of epidermis, dermis and hypodermis, echogenicity of dermis and the surface area of serrated hypodermis-dermis junction. Furthermore, the thigh circumference was measured; body mass index and cellulite severity were assessed based on photographs using Nürnberger-Müller's scale. Intradermal mesotherapy reduced severity of cellulite. The surface area of serrated hypodermis-dermis junction and hypodermis thickness decreased significantly as compared to baseline. Cellulite reduction was also confirmed by palpation, decreased thigh circumference and the Nürnberger-Müller's grade. There were no statistically significant changes in epidermis or dermis thickness, body weight and the BMI. Intradermal mesotherapy offers effective cellulite reduction. It is a simple and safe treatment, which makes it popular. Further research in mesotherapy is essential due to a limited number of published studies. Ultrasound is a useful method to monitor intradermal mesotherapy and assess its efficacy.

  8. Comparison of the therapeutic efficacy of intravenous dimenhydrinate and intravenous piracetam in patients with vertigo: a randomised clinical trial.

    Science.gov (United States)

    Doğan, Nurettin Özgür; Avcu, Nazire; Yaka, Elif; Yılmaz, Serkan; Pekdemir, Murat

    2015-07-01

    The present study aimed to compare the therapeutic efficacy of dimenhydrinate and piracetam in patients with vertigo. A blinded, parallel group, superiority, randomised clinical trial was carried out on patients who presented to the emergency department (ED) with vertigo. Healthy adult patients presenting to the ED with undifferentiated vertigo were included in the study. The efficacy of intravenous dimenhydrinate (100 mg) and intravenous piracetam (2000 mg) for reducing the intensity of vertigo was compared in two randomised treatment groups using a 10-point numeric rating scale (NRS). The determination of NRS scores was performed at presentation and at the 30th minute of presentation, after the study drug was implemented, both in immobile and ambulatory positions. The primary outcome variable was reduction in vertigo intensity documented on the NRS at the 30th minute after medication administration, analysed by intention to treat. A total of 94 patients were included in the randomisation (n=47 in both groups). The baseline NRS scores were 7.55±2.00 in the dimenhydrinate group and 8.19±1.79 in the piracetam group. The changes from baseline for dimenhydrinate and piracetam were 2.92±3.11 and 3.75±3.40 (difference -0.83 (95% CI -2.23 to 0.57)) in the immobile position and were 2.04±3.07 and 2.72±2.91 (difference -0.68 (95% CI -2.03 to 0.67)) in the ambulatory position. Rescue medication need was similar in both treatment groups (p=0.330), and only one adverse reaction was reported. We found no evidence of a difference between dimenhydrinate and piracetam in relieving the symptoms of vertigo. Clinical Trials Registration ID: NCT01890538. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. A comparison of the therapeutic and reactivating efficacy of newly developed bispyridinium compounds (K206, K269) with currently available oximes against tabun in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana; Bajgar, Jiri; Kuca, Kamil; Musilek, Kamil

    2008-12-01

    The potency of newly developed bispyridinium compounds (K206, K269) in reactivating tabun-inhibited acetylcholinesterase and eliminating tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies which determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime in blood but lower than the reactivating potency of trimedoxime and obidoxime in the diaphragm and brain. Nevertheless, the differences in reactivating efficacy of obidoxime, trimedoxime and K206 was not significant while the potency of K269 to reactivate tabun-inhibited acetylcholinesterase was significantly lower. Both newly developed oximes were also found to be relatively efficacious in elimination of the lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy corresponds to the therapeutic potency of obidoxime. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and to counteract lethal effects of tabun. Both newly developed oximes (K206, K269) are significantly more efficacious in reactivating tabun-inhibited AChE in rats and to eliminate lethal toxic effects of tabun in mice than the oxime HI-6 but their reactivating and therapeutic potency does not prevail over the effectiveness of currently available obidoxime and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

  10. Therapeutic efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum in Haiti after many decades of its use.

    Science.gov (United States)

    Okech, Bernard A; Existe, Alexandre; Romain, Jean R; Memnon, Gladys; Victor, Yves Saint; de Rochars, Madsen Beau; Fukuda, Mark

    2015-03-01

    Chloroquine (CQ) has been used for malaria treatment in Haiti for several decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a 42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was seasonal, with peak observations between October and January; 88% (107 of 121) of patients consented to participate. Sixty patients successfully completed the 42-day follow-up, whereas 47 patients withdrew consent or were lost to follow-up. The mean parasite density declined rapidly within the first few days after treatment. Seven patients did not clear their malaria infections and were clinically asymptomatic; therefore, they were considered late parasitological failures. About 90% (95% confidence interval = 84.20-97.90) of patients had no detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for recrudescence, reinfection, and CQ serum levels was not done in the seven patients, and therefore, their CQ resistance status is unresolved. CQ resistance surveillance by patient follow-up, in vitro drug sensitivity studies, and molecular markers is urgently needed in Haiti. © The American Society of Tropical Medicine and Hygiene.

  11. Simultaneous quantification of linezolid, tinidazole, norfloxacin, moxifloxacin, levofloxacin, and gatifloxacin in human plasma for therapeutic drug monitoring and pharmacokinetic studies in human volunteers.

    Science.gov (United States)

    Helmy, Sally A

    2013-12-01

    Linezolid may be administered in combination with norfloxacin, gatifloxacin, levofloxacin, moxifloxacin, and tinidazole for the treatment of various infections, such as urinary and respiratory tract infections, to improve the efficacy of the treatment or to reduce the duration of therapy. Knowledge of the antibiotic plasma concentrations combined with bacterial susceptibility evaluated in terms of minimum inhibitory concentration would optimize treatment efficacy while limiting the risk of dose-related adverse effects and avoiding suboptimal concentrations. A new high-performance liquid chromatography assay method was developed and validated for determination of the above-mentioned drugs in small samples of human plasma. After protein precipitation with acetonitrile:methanol (1:1, vol/vol), satisfactory separation was achieved on a Hypersil BDS C18 column (250 × 4.6 mm, 5 μm) using a mobile phase comprising 20 mM sodium dihydrogen phosphate-2 hydrate (pH = 3.2) and acetonitrile at a ratio of 75:25, vol/vol; the elution was isocratic at ambient temperature with a flow rate of 1.5 mL/min. The ultraviolet detector was set at 260 nm. The validated method was applied to assay real plasma samples used for pharmacokinetic studies and therapeutic drug monitoring of the selected drugs. The assay method described was found to be rapid, sensitive, reproducible, precise, and accurate. Linearity was demonstrated over the concentration ranges as follows: 0.1-30 μg/mL for linezolid and tinidazole; 0.05-5 μg/mL for norfloxacin; and 0.1-10 μg/mL for moxifloxacin, levofloxacin, and gatifloxacin (mean r = 0.9999, n = 12). The observed within- and between-day assay precisions were within 12.5%, whereas accuracy ranged between 92.0% and 112% for all the analytes. The lower limit of quantification was 0.1 μg/mL for all the analytes except norfloxacin which was 0.05 μg/mL. This assay method was valid within a wide range of plasma concentrations and may be proposed as a suitable

  12. The Consequence of Immune Suppressive Cells in the Use of Therapeutic Cancer Vaccines and Their Importance in Immune Monitoring

    Directory of Open Access Journals (Sweden)

    Matteo Vergati

    2011-01-01

    Full Text Available Evaluating the number, phenotypic characteristics, and function of immunosuppressive cells in the tumor microenvironment and peripheral blood could elucidate the antitumor immune response and provide information to evaluate the efficacy of cancer vaccines. Further studies are needed to evaluate the correlation between changes in immunosuppressive cells and clinical outcomes of patients in cancer vaccine clinical trials. This paper focuses on the role of T-regulatory cells, myeloid-derived suppressor cells, and tumor-associated macrophages in cancer and cancer immunotherapy and their role in immune monitoring.

  13. Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airway disease.

    Science.gov (United States)

    Royce, Simon G; Tominaga, Anna M; Shen, Matthew; Patel, Krupesh P; Huuskes, Brooke M; Lim, Rebecca; Ricardo, Sharon D; Samuel, Chrishan S

    2016-12-01

    Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. The present study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD, were either vehicle-treated (OVA alone) or treated with MSCs or AECs alone [intranasally (i.n.)-administered with 1×10(6) cells once weekly], RLX alone (i.n.-administered with 0.8 mg/ml daily) or a combination of MSCs or AECs and RLX from weeks 9-11 (n=6/group). Measures of AI, AWR and AHR were then assessed. OVA alone exacerbated AI, epithelial damage/thickness, sub-epithelial extracellular matrix (ECM) and total collagen deposition, markers of collagen turnover and AHR compared with that in saline-treated counterparts (all P<0.01 compared with saline-treated controls). RLX or AECs (but not MSCs) alone normalized epithelial thickness and partially diminished the OVA-induced fibrosis and AHR by ∼40-50% (all P<0.05 compared with OVA alone). Furthermore, the combination treatments normalized epithelial thickness, measures of fibrosis and AHR to that in normal mice, and significantly decreased AI. Although AECs alone demonstrated greater protection against the AAD-induced AI, AWR and AHR, compared with that of MSCs alone, combining RLX with MSCs or AECs reversed airway fibrosis and AHR to an even greater extent. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  14. Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat.

    Science.gov (United States)

    Kumar, Amit; Sharma, Pragya; Ali, Manjoor; Pandey, Badri Narain; Mishra, Kaushala Prasad

    2012-03-01

    This study examined the effect of liposomal encapsulation of (99m)Tc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium ((232)Th)-induced liver toxicity and its accumulation in rat animal model. (99m)Tc-DTPA was encapsulated in neutral (dipalmitoylphosphatidylcholine:cholesterol) and positively (dipalmitoylphosphatidylcholine:cholesterol:stearylamine) charged liposomes using thin film hydration method. Comparative efficacy of liposomal and free DTPA (11.2 mg/kg) was examined in terms of its effect on (232)Th accumulation and subsequent toxicity in the liver and blood of rat administered with (232)Th-nitrate (600 μg/kg). Organ distribution of free or liposomal (99m)Tc-DTPA was determined by solid scintillation counting and (232)Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy. Neutral liposomes encapsulated with (99m)Tc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- (99m)Tc-DTPA. Administration of (232)Th-nitrate to rat significantly increased the levels of liver toxicity markers and of oxidative injury, which were found to be restored more significantly by neutral liposomal-DTPA than free-DTPA. The accumulation of (232)Th in liver and blood of contaminated mice was found to be decreased more significantly by neutral liposomal-DTPA than by free-DTPA. Decorporation and consequent mitigation of (232)Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.

  15. Quantitative Evaluation of Therapeutic Efficacy of Endovenous Laser Treatment for Distal Varicose Veins by Tc-99m RBC Venography

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Song, Ki Hoon; Sim, Seung Joo; Kim, Ki Ho [College of Medicine, Univ. of Donga, Busan (Korea, Republic of)

    2003-07-01

    Endovenous laser treatment (EVLT) has been shown to be effective for elimination of greater saphenous (GSV) incompetence. While the result of GSV closure has been studied in detail, the effects in distal GSV and its tributaries following EVLT are still not completely understood. In addition, the optimal time for treatment of remaining varicose veins is not established. We evaluated the clinical and radiological changes of distal varicose veins after EVLT and determined the optimal time for additional treatment of distal varicose veins following EVLT by Tc-99m RBC. Forty GSV (30 patients) were treated with 940 nm or 810 nm diode laser at usual energy setting. Clinical and Duplex evaluation were performed at I week, and at various monthly intervals (2-6 months) following the initial treatment. Tc-99m venography was performed as usual protocol at I month and at every 3 months after EVLT. The distal varicose veins were quantified by determining the ratio of mean counts per pixel in the target and background areas and then comparing the pre-EVLT and post-EVLT values. Thirty-eight (95.0%) GSV were closed following EVLT and remained closed at 1-21 months follow-up examination. The reduction rate of distal varicose veins measured by Tc-99m venography was 22.8% at l month, 42.7% at 3 months, 61.5% at 6 months, and 72.4% at 9 months after EVLT. Fifteen legs (37.5%) required additional phlebectomy at 1 to 3 months after EVLT, while the others (62.5%) showed spontaneous regression of distal veins from one month during follow-up period. Therapeutic efficacy of EVLT for distal varicose vein can be well-evaluated quantitatively by Tc-99m RBC venography. Theses results suggest that after EVLT for GSV, the 'wait' policy would be necessary, rather than the 'wasting' of distal veins concurrently with EVLT.

  16. Monitoring of high-intensity focused ultrasound treatment by shear wave elastography induced by two-dimensional-array therapeutic transducer

    Science.gov (United States)

    Iwasaki, Ryosuke; Takagi, Ryo; Nagaoka, Ryo; Jimbo, Hayato; Yoshizawa, Shin; Saijo, Yoshifumi; Umemura, Shin-ichiro

    2016-07-01

    Shear wave elastography (SWE) is expected to be a noninvasive monitoring method of high-intensity focused ultrasound (HIFU) treatment. However, conventional SWE techniques encounter difficulty in inducing shear waves with adequate displacements in deep tissue. To observe tissue coagulation at the HIFU focal depth via SWE, in this study, we propose using a two-dimensional-array therapeutic transducer for not only HIFU exposure but also creating shear sources. The results show that the reconstructed shear wave velocity maps detected the coagulated regions as the area of increased propagation velocity even in deep tissue. This suggests that “HIFU-push” shear elastography is a promising solution for the purpose of coagulation monitoring in deep tissue, because push beams irradiated by the HIFU transducer can naturally reach as deep as the tissue to be coagulated by the same transducer.

  17. Human papillomavirus 16 L1-E7 chimeric virus like particles show prophylactic and therapeutic efficacy in murine model of cervical cancer.

    Science.gov (United States)

    Sharma, Chandresh; Dey, Bindu; Wahiduzzaman, Mohammed; Singh, Neeta

    2012-08-03

    Cervical cancer is found to be associated with human papillomavirus (HPV) infection, with HPV16 being the most prevalent. An effective vaccine against HPV can thus, be instrumental in controlling cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infection as well as cell-mediated immunity to eliminate established infection. In this study, we have generated a potential preventive and therapeutic candidate vaccine against HPV16. We expressed and purified recombinant HPV16 L1(ΔN26)-E7(ΔC38) protein in E. coli which was assembled into chimeric virus like particles (CVLPs) in vitro. These CVLPs were able to induce neutralizing antibodies and trigger cell-mediated immune response, in murine model of cervical cancer, exhibiting antitumor efficacy. Hence, this study has aimed to provide a vaccine candidate possessing both, prophylactic and therapeutic efficacy against HPV16 associated cervical cancer.

  18. An Analysis of a Novel, Short-Term Therapeutic Psychoeducational Program for Children and Adolescents with Chronic Neurological Illness and Their Parents; Feasibility and Efficacy

    OpenAIRE

    Joo, Bonglim; Lee, Young-Mock; Kim, Heung Dong; Eom, Soyong

    2017-01-01

    The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children (n = 8) and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological como...

  19. Phase Ⅲ Clinical Trials of the Cell Differentiation Agent-2 (CDA-2): Therapeutic Efficacy on Breast Cancer, Non-Small Cell Lung Cancer and Primary Hepatoma

    Institute of Scientific and Technical Information of China (English)

    Fengyi Feng; Mingzhong Li; Yunzhong Zhu; Meizhen Zhou; Jun Ren; Yetao Gao; Jingpo Zhao; Rongsheng Zheng; Wenhua Zhao; Zhiqiang Meng; Fang Li; Qing Li; Qizhong Zhang; Dongli Zhao; Liyan Xu; Yongqiang Zhang; Yanjun Zhang; Zhenjiu Wang; Shuanqi Liu; Ming C. Liau; Changquan Ling; Yang Zhang; Fengzhan Qin; Huaqing Wang; Wenxia Huang; Shunchang Jiao; Qiang Chen

    2005-01-01

    OBJECTIVE The objective of this study was to explore the effect of CDA-2, a selective inhibitor of abnormal methylation enzymes in cancer cells, on the therapeutic efficacy of cytotoxic chemotherapy.METHODS Advanced cancer patients, all of whom had previously undergone chemotherapy, were randomly divided into 2 groups, one receiving chemotherapy only as the control group, and the other receiving CDA-2 in addition to chemotherapy as the combination group. The therapeutic efficacies and the toxic manifestations of the 2 groups were compared based on the WHO criteria.RESULTS Of 454 cancer patients enrolled in phase Ⅲ clinical trials of CDA-2, 80, 188, and 186 were breast cancer,NSCLC, and primary hepatoma patients, respectively.Among them 378 patients completed treatments according to the protocols. The results showed that the overall effective rate of the combination group was 2.6 fold that of the control group, 4.8 fold in the case of breast cancer, 2.3 fold in the case of primary hepatoma, and 2.2 fold in the case of NSCLC. Surprisingly, the combination therapy appeared to work better for stage Ⅳ than stage Ⅲ patients. CDA-2 did not contribute additional toxicity. On the contrary, it reduced toxic manifestations of chemotherapy, particularly regarding white blood cells, nausea and vomiting.CONCLUSION Modulation of abnormal methylation enzymes by CDA-2 is definitely helpful to supplement chemotherapy. It significantly increased the therapeutic efficacy and reduced the toxic manifestation of cytotoxic chemotherapy on breast cancer and NSCLC.

  20. Optimized high performance liquid chromatography-ultraviolet detection method using core-shell particles for the therapeutic monitoring of methotrexate$

    Institute of Scientific and Technical Information of China (English)

    Milagros Montemurro; María M. De Zan n; Juan C. Robles

    2016-01-01

    Methotrexate (MTX) is an antineoplastic drug, and due to its high toxicity, the therapeutic drug mon-itoring is strictly conducted in the clinical practice. The chemometric optimization and validation of a high performance liquid chromatography (HPLC) method using core–shell particles is presented for the determination of MTX in plasma during therapeutic monitoring. Experimental design and response surface methodology (RSM) were applied for the optimization of the chromatographic system and the analyte extraction step. A Poroshell 120 EC-C18 (3.0 mm ? 75 mm, 2.7μm) column was used to obtain a fast and efficient separation in a complete run time of 4 min. The optimum conditions for the chroma-tographic system resulted in a mobile phase consisting of acetic acid/sodium acetate buffer solution (85.0 mM, pH¼4.00) and 11.2%of acetonitrile at a flow rate of 0.4 mL/min. Selectivity, linearity, accuracy and precision were demonstrated in a range of 0.10–6.0 mM of MTX. The application of the optimized method required only 150 mL of patient plasma and a low consumption of solvent to provide rapid re-sults.

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

    Science.gov (United States)

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

    2017-08-08

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

  2. Monitoring Disease Progression and Therapeutic Response in a Disseminated Tumor Model for Non-Hodgkin Lymphoma by Bioluminescence Imaging

    Directory of Open Access Journals (Sweden)

    Margarethe Köberle

    2015-07-01

    Full Text Available Xenograft tumor models are widely studied in cancer research. Our aim was to establish and apply a model for aggressive CD20-positive B-cell non-Hodgkin lymphomas, enabling us to monitor tumor growth and shrinkage in a noninvasive manner. By stably transfecting a luciferase expression vector, we created two bioluminescent human non-Hodgkin lymphoma cell lines, Jeko1(luci and OCI-Ly3(luci, that are CD20 positive, a prerequisite to studying rituximab, a chimeric anti-CD20 antibody. To investigate the therapy response in vivo, we established a disseminated xenograft tumor model injecting these cell lines in NOD/SCID mice. We observed a close correlation of bioluminescence intensity and tumor burden, allowing us to monitor therapy response in the living animal. Cyclophosphamide reduced tumor burden in mice injected with either cell line in a dose-dependent manner. Rituximab alone was effective in OCI-Ly3(luci-injected mice and acted additively in combination with cyclophosphamide. In contrast, it improved the therapeutic outcome of Jeko1(luci-injected mice only in combination with cyclophosphamide. We conclude that well-established bioluminescence imaging is a valuable tool in disseminated xenograft tumor models. Our model can be translated to other cell lines and used to examine new therapeutic agents and schedules.

  3. Post-discharge electrocardiogram Holter monitoring in recently hospitalised individuals with chronic atrial fibrillation to enhance therapeutic monitoring and identify potentially predictive phenotypes.

    Science.gov (United States)

    Ball, Jocasta; Carrington, Melinda J; Thompson, David R; Horowitz, John D; Stewart, Simon

    2015-10-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia managed in clinical practice. Maintenance of intended rate or rhythm control following hospitalisation is a key therapeutic goal. The purpose of this study was to assess post-discharge maintenance of intended AF control and classify potentially predictive heart rate (HR) phenotypes via electrocardiogram (ECG) Holter monitoring. In a sub-study of a multicentre randomised controlled trial comparing AF-specific management with usual care, 24-hour ECG Holter monitoring was undertaken in 133 patients 7-14 days post-discharge. Intended rate and rhythm control were compared to Holter data. Analysis of the frequency distribution of mean hour-to-hour differences identified those with labile HRs. Mean age was 71 ± 10 years, 67 (50%) were male and mean HR was 72 ± 14 bpm. Most (89%) had persistent AF (median time in AF=39% (IQR 0-100%)). Uncontrolled HR (>90 bpm for >10% of recording) occurred in 35 (26%) patients and 49 (37%) patients did not achieve their intended rate (n=26) or rhythm control (n=23). Patients in the upper quartile of mean hour-to-hour HR variability were identified as persistently labile (n=33). A further group (n=22) with periodically labile HRs was identified. Those with coronary artery disease (OR 0.34; 95% CI 0.13-0.91, p=0.033) or renal disease/dysfunction (OR 0.24; 95% CI 0.06-0.98, p=0.047) were less likely to demonstrate HR stability (n=78). Post-discharge ECG Holter monitoring of AF patients represents a valuable tool to identify deviations in intended rhythm/rate control and adjust therapeutic management accordingly. It may also identify individuals who demonstrate labile HRs. © The European Society of Cardiology 2014.

  4. A retrospective exploration of patient-ventilator monitoring intensity, therapeutic intervention intensity, and compliance with lung protective guidelines in a cohort of patients with adult respiratory distress syndrome.

    Science.gov (United States)

    Jones, Terry L

    2011-03-01

     The current approach to mechanical ventilation for adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) involves maintaining key patient-ventilator parameters within established lung protective targets. Monitoring is part of the processes of nursing care believed to guide therapeutic intervention and facilitate compliance with these targets. Empirical relationships between monitoring, therapeutic intervention, and compliance with these practice guidelines have not been adequately explored.  A retrospective observational design was used to explore relationships between monitoring intensity, therapeutic intervention intensity, and compliance with a lung protective philosophy of mechanical ventilation in a cohort of patients with ARDS or ALI. Compliance with lung protective targets was measured as the proportion of time oxygen saturation, alveolar distending pressure, and tidal volume were maintained within recommended guidelines as evidenced by medical record documentation. Monitoring intensity and therapeutic intervention intensity were based on the frequency of recorded assessments and interventions in the medical record.  Monitoring intensity correlated positively with both severity of illness (r = 0.39) and with therapeutic intervention intensity (r = 0.30), and was inversely related to compliance with lung protective guidelines (CLPG) (r = -0.34). A regression model including monitoring intensity, severity of illness, risk for abdominal hypertension, and CLPG was statistically significant (p = 0.02) but explained little of the variance in compliance with lung protective parameters (R2 = 0.13).  Compliance with recommended lung protective parameters in the absence of standardized monitoring and intervention protocols is suboptimal. Preliminary evidence of positive relationships between monitoring and both severity of illness and therapeutic intervention was established. Control for nursing and physician practice variation is

  5. In vivo small animal imaging for early assessment of therapeutic efficacy of photodynamic therapy for prostate cancer

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Chen, Xiang; Meyers, Joseph; Mulvilhill, John; Feyes, Denise; Edgehouse, Nancy; Duerk, Jeffrey L.; Pretlow, Thomas G.; Oleinick, Nancy L.

    2007-03-01

    We are developing in vivo small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center. In this study, we are developing magnetic resonance imaging (MRI) techniques that provide therapy monitoring and early assessment of tumor response to PDT. We generated human prostate cancer xenografts in athymic nude mice. For the imaging experiments, we used a highfield 9.4-T small animal MR scanner (Bruker Biospec). High-resolution MR images were acquired from the treated and control tumors pre- and post-PDT and 24 hr after PDT. We utilized multi-slice multi-echo (MSME) MR sequences. During imaging acquisitions, the animals were anesthetized with a continuous supply of 2% isoflurane in oxygen and were continuously monitored for respiration and temperature. After imaging experiments, we manually segmented the tumors on each image slice for quantitative image analyses. We computed three-dimensional T2 maps for the tumor regions from the MSME images. We plotted the histograms of the T2 maps for each tumor pre- and post-PDT and 24 hr after PDT. After the imaging and PDT experiments, we dissected the tumor tissues and used the histologic slides to validate the MR images. In this study, six mice with human prostate cancer tumors were imaged and treated at the Case Center for Imaging Research. The T2 values of treated tumors increased by 24 +/- 14% 24 hr after the therapy. The control tumors did not demonstrate significant changes of the T2 values. Inflammation and necrosis were observed within the treated tumors 24 hour after the treatment. Preliminary results show that Pc 4-PDT is effective for the treatment of human prostate cancer in mice. The small animal MR

  6. Investigation of the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma cells.

    Directory of Open Access Journals (Sweden)

    Nesrin Sabha

    Full Text Available Vestibular schwannomas (VS are a common posterior fossa brain tumor, and though benign can cause significant morbidity, particularly loss of hearing, tinnitus, vertigo and facial paralysis. The current treatment options for VS include microsurgical resection, stereotactic radiosurgery or close surveillance monitoring, with each treatment option carrying associated complications and morbidities. Most importantly, none of these options can definitively reverse hearing loss or tinnitus. Identification of a novel medical therapy, through the use of targeted molecular inhibition, is therefore a highly desirable treatment strategy that may minimize complications arising from both tumor and treatment and more importantly be suitable for patients whose options are limited with respect to surgical or radiosurgical interventions. In this study we chose to examine the effect of Nilotinib on VS. Nilotinib (Tasigna® is a second-generation receptor tyrosine kinase (RTK inhibitor with a target profile similar to that of imatinib (Gleevec®, but increased potency, decreased toxicity and greater cellular and tissue penetration. Nilotinib targets not only the BCR-ABL oncoprotein, but also platelet-derived growth factor (PDGF receptor signalling. In this preclinical study, the human NF2-null schwannoma cell line HEI-193 subjected to nilotinib inhibition demonstrated decreased viability, proliferation and anchorage-independent growth, and increased apoptosis. A daily dose of nilotinib for 5 days inhibited HEI-I93 proliferation at a clinically-relevant concentration in a dose-dependent manner (IC(50 3-5 µmol/L in PDGF-stimulated cells. These anti-tumorigenic effects of nilotinib were correlated to inhibited activation of PDGFR-α and PDGFR-β and major downstream signalling pathways. These experiments support a therapeutic potential for Nilotinib in VS.

  7. Investigating the efficacy of subharmonic aided pressure estimation for portal vein pressures and portal hypertension monitoring.

    Science.gov (United States)

    Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Merton, Daniel A; Liu, Ji-Bin; Zhou, Jian-Hua; Wang, Hsin-Kai; Park, Suhyun; Dianis, Scott; Chalek, Carl L; Lin, Feng; Thomenius, Kai E; Brown, Daniel B; Forsberg, Flemming

    2012-10-01

    The efficacy of using subharmonic emissions from Sonazoid microbubbles (GE Healthcare, Oslo, Norway) to track portal vein pressures and pressure changes was investigated in 14 canines using either slow- or high-flow models of portal hypertension (PH). A modified Logiq 9 scanner (GE Healthcare, Milwaukee, WI, USA) operating in subharmonic mode (f(transmit): 2.5 MHz, f(receive): 1.25 MHz) was used to collect radiofrequency data at 10-40% incident acoustic power levels with 2-4 transmit cycles (in triplicate) before and after inducing PH. A pressure catheter (Millar Instruments, Inc., Houston, TX, USA) provided reference portal vein pressures. At optimum insonification, subharmonic signal amplitude changes correlated with portal vein pressure changes; r ranged from -0.82 to -0.94 and from -0.70 to -0.73 for PH models considered separately or together, respectively. The subharmonic signal amplitudes correlated with absolute portal vein pressures (r: -0.71 to -0.79). Statistically significant differences between subharmonic amplitudes, before and after inducing PH, were noted (p ≤ 0.01). Portal vein pressures estimated using subharmonic aided pressure estimation did not reveal significant differences (p > 0.05) with respect to the pressures obtained using the Millar pressure catheter. Subharmonic-aided pressure estimation may be useful clinically for portal vein pressure monitoring.

  8. Improving the Accuracy of Outdoor Educators' Teaching Self-Efficacy Beliefs through Metacognitive Monitoring

    Science.gov (United States)

    Schumann, Scott; Sibthorp, Jim

    2016-01-01

    Accuracy in emerging outdoor educators' teaching self-efficacy beliefs is critical to student safety and learning. Overinflated self-efficacy beliefs can result in delayed skilled development or inappropriate acceptance of risk. In an outdoor education context, neglecting the accuracy of teaching self-efficacy beliefs early in an educator's…

  9. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  10. A Database of Reaction Monitoring Mass Spectrometry Assays for Elucidating Therapeutic Response in Cancer

    Science.gov (United States)

    Remily-Wood, Elizabeth R.; Liu, Richard Z.; Xiang, Yun; Chen, Yi; Thomas, C. Eric; Rajyaguru, Neal; Kaufman, Laura M.; Ochoa, Joana E.; Hazlehurst, Lori; Pinilla-Ibarz, Javier; Lancet, Jeffrey; Zhang, Guolin; Haura, Eric; Shibata, David; Yeatman, Timothy; Smalley, Keiran S.M.; Dalton, William S.; Huang, Emina; Scott, Ed; Bloom, Gregory C.; Eschrich, Steven A.; Koomen, John M.

    2012-01-01

    Purpose The Quantitative Assay Database (QuAD), http://proteome.moffitt.org/QUAD/, facilitates widespread implementation of quantitative mass spectrometry in cancer biology and clinical research through sharing of methods and reagents for monitoring protein expression and modification. Experimental Design Liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM) assays are developed using SDS-PAGE fractionated lysates from cancer cell lines. Pathway maps created using GeneGO Metacore provide the biological relationships between proteins and illustrate concepts for multiplexed analysis; each protein can be selected to examine assay development at the protein and peptide level. Results The coupling of SDS-PAGE and LC-MRM screening has been used to detect 876 peptides from 218 cancer-related proteins in model systems including colon, lung, melanoma, leukemias, and myeloma, which has led to the development of 95 quantitative assays including stable-isotope labeled peptide standards. Methods are published online and peptide standards are made available to the research community. Protein expression measurements for heat shock proteins, including a comparison with ELISA and monitoring response to the HSP90 inhibitor, 17-DMAG, are used to illustrate the components of the QuAD and its potential utility. Conclusions and Clinical Relevance This resource enables quantitative assessment of protein components of signaling pathways and biological processes and holds promise for systematic investigation of treatment responses in cancer. PMID:21656910

  11. Comparison of reactivating and therapeutic efficacy of two salts of the oxime HI-6 against tabun, soman and cyclosarin in rats.

    Science.gov (United States)

    Kassa, Jiri; Jun, Daniel; Kuca, Kamil; Bajgar, Jiri

    2007-11-01

    The reactivating and therapeutic efficacy of two salts of the oxime HI-6 (dichloride and dimethanesulphonate) against chosen nerve agents (tabun, soman and cyclosarin) was compared in rats. The potency of both salts of HI-6 to decrease the acute toxicity of tabun, soman and cyclosarin was similar in nerve agent-poisoned rats. While the potency of HI-6 dichloride and HI-6 dimethanesulphonate to counteract acute toxic effects of tabun is rather low, both salts of HI-6 were able to decrease the acute toxicity of soman two times and acute toxicity of cyclosarin more than three times. The therapeutic efficacy of both salts of the oxime HI-6 corresponds to their reactivating potency. While the reactivating efficacy of HI-6 dichloride as well as HI-6 dimethanesulphonate against tabun was negligible, their potency to reactivate soman-inhibited acetylcholinesterase and cyclosarin-inhibited acetylcholinesterase in peripheral (blood) and central (brain) compartment was relatively high. HI-6 dichloride showed a somewhat higher potency to reactivate tabun-inhibited acetylcholinesterase in brain, and soman-inhibited acetylcholinesterase in blood and brain than HI-6 dimethanesulphonate but the differences were not significant. Thus, the replacement of dichloride anion by dimethanesulphonate anion in the oxime HI-6 does not influence the therapeutic and reactivating efficacy of the oxime HI-6 against nerve agents. In addition, the higher solubility and stability of HI-6 dimethanesulphonate in comparison with HI-6 dichloride makes it possible to increase the dose and thus, the effectiveness of the oxime HI-6 in the antidotal treatment of acute nerve agent poisonings.

  12. Noninvasive Monitoring of Pneumococcal Meningitis and Evaluation of Treatment Efficacy in an Experimental Mouse Model*

    Directory of Open Access Journals (Sweden)

    Jagath L. Kadurugamuwa

    2005-04-01

    Full Text Available Noninvasive real-time in vivo bioluminescent imaging was used to assess the spread of Streptococcus pneumoniae throughout the spinal cord and brain during the acute stages of bacterial meningitis. A mouse model was established by lumbar (LP or intracisternal (IC injection of bioluminescent S. pneumoniae into the subarachnoid space. Bacteria replicated initially at the site of inoculation and spread progressively from the spinal cord to the brain or from the brain down to the cervical part of the spinal column and to the lower vertebral levels. After 24 hr, animals showed strong bioluminescent signals throughout the spinal canal, indicating acute meningitis of the intracranial and intraspinal meninges. A decline in bacterial cell viability, as judged by a reduction in the bioluminescent signal, was observed over time in animals treated with ceftriaxone, but not in untreated groups. Mice treated with the antibiotic survived infection, whereas all mice in untreated groups became moribund, first in the IC group then in the LP group. No untreated animal survived beyond 48 hr after induction of infection. Colony counts of infected cerebrospinal fluid (CSF correlated positively with bioluminescent signals. This methodology is especially appealing because it allows detecting infected mice as early as 3 hr after inoculation, provide temporal, sequential, and spatial distribution of bacteria within the brain and spinal cord throughout the entire disease process and the rapid monitoring of treatment efficacy in a nondestructive manner. Moreover, it avoids the need to sacrifice the animals for CSF sampling and the potential manipulative damage that can occur with other conventional methods.

  13. Simple and sensitive high performance liquid chromatography method with fluorescence detection for therapeutic drug monitoring of topiramate.

    Science.gov (United States)

    Milosheska, Daniela; Vovk, Tomaž; Grabnar, Iztok; Roškar, Robert

    2015-01-01

    A simple, sensitive, accurate, precise and inexpensive HPLC method with fluorescence detection, suitable for routine therapeutic drug monitoring (TDM) of an antiepileptic drug topiramate, was developed and validated. The determination of plasma topiramate concentration was carried out after precolumn derivatization, using 4-chloro-7-nitrobenzofurazan as a fluorescent labeling agent and bendroflumethiazide as an internal standard. The standard calibration curve was linear over the concentration range of 0.01-24 μg/mL (r² > 0.9998). The intra- and inter-day accuracies expressed as bias were from 1.4 to 9.9% and from 1.9 to 10.2%, respectively. The intra- and inter-day precisions were below 7.9% and 2.7%, respectively. The validated method was applied for the measurement of plasma topiramate concentrations in patients with epilepsy. The reported method is appropriate for TDM of topiramate as well as for pharmacokinetic and bioequivalence studies.

  14. Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir.

    LENUS (Irish Health Repository)

    Caswell, R J

    2011-01-01

    The pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and\\/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence.

  15. Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling for Therapeutic Drug Monitoring in Children

    Science.gov (United States)

    Martial, Lisa C.; Aarnoutse, Rob E.; Schreuder, Michiel F.; Henriet, Stefanie S.; Brüggemann, Roger J. M.; Joore, Manuela A.

    2016-01-01

    Dried blood spot (DBS) sampling for the purpose of therapeutic drug monitoring can be an attractive alternative for conventional blood sampling, especially in children. This study aimed to compare all costs involved in conventional sampling versus DBS home sampling in two pediatric populations: renal transplant patients and hemato-oncology patients. Total costs were computed from a societal perspective by adding up healthcare cost, patient related costs and costs related to loss of productivity of the caregiver. Switching to DBS home sampling was associated with a cost reduction of 43% for hemato-oncology patients (€277 to €158) and 61% for nephrology patients (€259 to €102) from a societal perspective (total costs) per blood draw. From a healthcare perspective, costs reduced with 7% for hemato-oncology patients and with 21% for nephrology patients. Total savings depend on the number of hospital visits that can be avoided by using home sampling instead of conventional sampling. PMID:27941974

  16. Therapeutic efficacy of anti-dandruff shampoos: a randomized clinical trial comparing products based on potentiated zinc pyrithione and zinc pyrithione/climbazole.

    Science.gov (United States)

    Schwartz, J R; Bacon, R A; Shah, R; Mizoguchi, H; Tosti, A

    2013-08-01

    Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti-fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti-fungal shampoos are maximizing bio-availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches - maximization of bio-availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material. The anti-fungal potency of shampoos representing each of these approaches was evaluated in vitro using a standard microbiology method. Spatial delivery of ZPT particles in the follicular infundibulum was assessed in vivo using a novel confocal microscopy methodology. Clinical efficacy was assessed in a randomized, double-blind trial involving 620 male and female subjects using scalp flaking and epidermal histamine level as endpoints. The shampoo formula with maximized ZPT bio-availability known as the Potentiated ZPT formula exhibited greater anti-fungal potency than the Dual Active shampoo containing both ZPT and climbazole. The Potentiated ZPT formula also delivered more ZPT to the lower infundibulum than the Dual Active shampoo. A 4-week treatment with the Potentiated ZPT formula resulted in superior clinical efficacy compared with the Dual Active product at all 4 weekly time points for both flaking and epidermal histamine endpoints. These results highlight the critical role that the shampoo vehicle plays in realizing full potency of active materials. By optimizing the delivery vehicle, the enhanced anti-fungal potency and the maximized spatial delivery of active materials result in greater symptomatic improvement than a product with two active materials. The therapeutic efficacy of a product based on a complex delivery vehicle such as a shampoo

  17. A comparison of the reactivating and therapeutic efficacy of newly developed bispyridinium oximes (K250, K251) with commonly used oximes against tabun in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana; Bajgar, Jiri; Kuca, Kamil; Musilek, Kamil; Kopelikova, Irena

    2009-08-01

    The potency of newly developed bispyridinium compounds (K250, K251) in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with the oxime HI-6 but it is significantly lower than the reactivating effects of obidoxime and trimedoxime, especially in diaphragm and brain. Both newly developed oximes were also found to be able to slightly reduce lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy is higher than the potency of the oxime HI-6 but it is lower than the therapeutic effects of trimedoxime and obidoxime. Thus, the reactivating and therapeutic potency of both newly developed oximes (K250, K251) does not prevail over the effectiveness of currently available oximes and, therefore, they are not suitable for their replacement for the treatment of acute tabun poisoning.

  18. Biochemical changes associated with ascorbic acid–cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Amenla Longchar

    2015-01-01

    Full Text Available Cisplatin is one of the well-established anticancer drugs being used against a wide spectrum of cancers. However, full therapeutic efficacy of the drug is limited due to development of various toxicities in the host. This study examines the comparative therapeutic effectiveness and toxicities of cisplatin alone and in combination of dietary ascorbic acid (AA in ascites Dalton's lymphoma-bearing mice. The findings show that the combination treatment of mice with ascorbic acid plus cisplatin has much better therapeutic efficacy against murine ascites Dalton's lymphoma (DL in comparison to cisplatin alone and this may involve a decrease in reduced glutathione (GSH, catalase activity and increased lipid peroxidation (LPO in Dalton's lymphoma tumor cells. At the same time, combination treatment indicates a protective role of ascorbic acid against cisplatin-induced tissue toxicities (side effects in the hosts. Cisplatin-induced histopathological changes in liver, kidney and testes were decreased after combination treatment. The analysis of renal function test (RFT, liver function test (LFT and sperm abnormalities also suggest an improvement in these parameters after combination treatment. Therefore, it may be concluded that the increased GSH level, catalase activity and decreased LPO in the tissues, i.e., liver, kidney and testes after combination treatment may be involved in its protective ability against cisplatin-induced tissue toxicities in the host.

  19. Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring

    Directory of Open Access Journals (Sweden)

    Michaëlsson Karl

    2004-04-01

    Full Text Available Abstract Background The ABC transporter P-glycoprotein (P-gp is recognized as a site for drug-drug interactions and provides a mechanistic explanation for clinically relevant pharmacokinetic interactions with digoxin. The question of whether several P-gp inhibitors may have additive effects has not yet been addressed. Methods We evaluated the effects on serum concentrations of digoxin (S-digoxin in 618 patients undergoing therapeutic drug monitoring. P-gp inhibitors were classified as Class I, with a known effect on digoxin kinetics, or Class II, showing inhibition in vitro but no documented effect on digoxin kinetics in humans. Mean S-digoxin values were compared between groups of patients with different numbers of coadministered P-gp inhibitors by a univariate and a multivariate model, including the potential covariates age, sex, digoxin dose and total number of prescribed drugs. Results A large proportion (47% of the digoxin patients undergoing therapeutic drug monitoring had one or more P-gp inhibitor prescribed. In both univariate and multivariate analysis, S-digoxin increased in a stepwise fashion according to the number of coadministered P-gp inhibitors (all P values Conclusions Polypharmacy may lead to multiple drug-drug interactions at the same site, in this case P-gp. The S-digoxin levels increased in a stepwise fashion with an increasing number of coadministered P-gp inhibitors in patients taking P-gp inhibitors and digoxin concomitantly. As coadministration of digoxin and P-gp inhibitors is common, it is important to increase awareness about P-gp interactions among prescribing clinicians.

  20. Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles.

    Science.gov (United States)

    Warsame, Marian; Hassan, Abdillahi Mohamed; Barrette, Amy; Jibril, Ali Mohamed; Elmi, Husein Haji; Arale, Abdulkadir Mohamed; Mohammady, Hanan El; Nada, Rania A; Amran, Jamal Ghilan Hefzullah; Muse, Abdikarim; Yusuf, Fahmi Essa; Omar, Abdiqani Sheikh

    2015-04-01

    Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first-line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011. Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) genes. The proportion of PCR-corrected treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR = 5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96). The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy. © 2015 John Wiley & Sons Ltd.

  1. Comparative therapeutic efficacy of rhenium-188 radiolabeled-liposome and 5-fluorouracil in LS-174T human colon carcinoma solid tumor xenografts.

    Science.gov (United States)

    Hsu, Chin-Wei; Chang, Ya-Jen; Chang, Chih-Hsien; Chen, Liang-Cheng; Lan, Keng-Li; Ting, Gann; Lee, Te-Wei

    2012-10-01

    Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

  2. Development of a wireless intra-ocular pressure monitoring system for incorporation into a therapeutic glaucoma drainage implant

    Science.gov (United States)

    Kakaday, Tarun; Plunkett, Malcolm; McInnes, Steven; Li, Jim S. Jimmy; Voelcker, Nicolas H.; Craig, Jamie E.

    2008-12-01

    Glaucoma is a common cause of blindness. Wireless, continuous monitoring of intraocular pressure (IOP) is an important, unsolved goal in managing glaucoma. An IOP monitoring system incorporated into a glaucoma drainage implant (GDI) overcomes the design complexity associated with incorporating a similar system in a more confined space within the eye. The device consists of a micro-electro-mechanical systems (MEMS) based capacitive pressure sensor integrated with an inductor printed directly onto a polyimide printed circuit board (PCB). The device is designed to be incorporated onto the external plate of a therapeutic GDI. The resonance frequency changes as a function of IOP, and is tracked remotely using a spectrum analyzer. A theoretical model for the reader antenna was developed to enable maximal inductive coupling with the IOP sensor implant. Pressure chamber tests indicate that the sensor implant has adequate sensitivity in the IOP range with excellent reproducibility over time. Additionally, we show that sensor sensitivity does not change significantly after encapsulation with polydimethylsiloxane (PDMS) to protect the device from fluid environment. In vitro experiments showed that the signal measured wirelessly through sheep corneal and scleral tissue was adequate indicating potential for using the system in human subjects.

  3. A comparison of the reactivating and therapeutic efficacy of chosen combinations of oximes with individual oximes against VX in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Sepsova, Vendula; Caisberger, Filip; Bajgar, Jiri

    2011-10-01

    The ability of 2 combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate VX-inhibited acetylcholinesterase and reduce acute toxicity of VX was compared with the reactivating and therapeutic efficacy of antidotal treatment involving a single oxime (HI-6, trimedoxime, K203) in rats and mice. Our results showed that the reactivating efficacy of both combinations of oximes studied in rats is significantly higher than the reactivating efficacy of all individual oximes in diaphragm and roughly corresponds to the most effective individual oxime in blood and brain. Both combinations of oximes were found to be more effective in the reduction of acute lethal toxicity of VX in mice than the antidotal treatment involving the most efficacious individual oxime although the difference is not significant. Based on the obtained data, we can conclude that the antidotal treatment involving the chosen combinations of oximes brings benefit for the reactivation of VX-inhibited acetylcholinesterase in rats and for the antidotal treatment of VX-induced acute poisoning in mice.

  4. Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Radu M. Nanau

    2015-06-01

    Full Text Available Background: The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. Methods: A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010–2015. The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Findings: Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

  5. Laser-induced breakdown spectroscopy of dental lesions: diagnostic and therapeutic monitoring tool

    Science.gov (United States)

    Borisova, Ekaterina; Uzunov, Tzonko; Penev, Dimitar; Genova, Tsanislava; Avramov, Latchezar

    2016-01-01

    The carious decay develops a tiny area of demineralization on the enamel, which could be detected by element analytic techniques such as laser-induced breakdown spectroscopy (LIBS). That demineralization can quickly turn into a large lesion inside the tooth, it is often discovered too late to prevent the kind of decay that leads to cavities. The same optical LIBS detection approach could be used for monitoring of the caries removal using laser ablation or drilling techniques. For LIBS measurements we applied LIBS 2500Plus (Ocean Optics Inc., Dunedin, USA) system, which consists of seven spectrometric channels, covering spectral region from 200 to 980 nm, which optical resolution 0,05 nm, the spectrometers are connected with sample fiber bundle for 7-channels spectral system to the chamber for solid and liquid samples, Q-switched Nd:YAG laser, at 1 064 nm, with energy per pulse - 40 mJ, which is applied to induce plasma in the samples. LIBS spectra were obtained after single shot of the laser in the region of pathology. Samples investigated by LIBS are extracted teeth from patients, with periodontal problems on different stage of carious lesions, and their LIBS spectra are compared with the LIBS signals obtained from normal enamel and dentine tissues to receive complete picture of the carious lesion development. The major line of our investigations is related to the development of a methodology for real-time optical feedback control during selective ablation of tooth tissues using LIBS. Tooth structures, with and without pathological changes, are compared and their LIBS element analysis is used to differentiate major changes, which occur during tooth carious process and growth.

  6. Therapeutic monitoring of amphotericin B in Saudi ICU patients using UPLC MS/MS assay.

    Science.gov (United States)

    Al-Quadeib, Bushra T; Radwan, Mahasen A; Siller, Lidija; Mutch, Elaine; Horrocks, Ben; Wright, Matthew; Alshaer, Abdulaziz

    2014-12-01

    Amphotericin B (AmB) is the first-line agent for the treatment of life-threatening invasive fungal infections. The aim of this study was to monitor AmB in critically ill Saudi patients in ICU after i.v. administration of 0.68 ± 0.1 mg/kg/day Fungizone®. A selective, sensitive and precise UPLC MS/MS method was developed to measure AmB concentrations in these patients. Seven ICU patients with creatinine clearance (ClCr) >40 mL/min were included. AmB levels were analyzed using a Waters Aquity UPLC MS/MS system, a BEH Shield RP18 column and detection via electrospray ionization source with positive ionization mode. The precision and accuracy of the developed UPLC method in the concentration range of 200-4000 ng/mL show no significant difference among inter- and-intra-day analysis (p > 0.05). Linearity was observed over the investigated range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of AmB in these patients, at steady state, showed a high terminal half-life of 124.6 ± 73.4 h, with a highest concentration of 513.9 ± 281.1 ng/mL, a lowest concentration 316.4 ± 129.0 ng/mL and a mean clearance 91.1 ± 39.2 mL/h/kg. The pharmacokinetics of AmB in critically ill Saudi patients in ICU was studied using a fully validated assay. A weak correlation (r = -0.22) of AmB Cl with ClCr was obtained, which suggests the need for further investigation in a larger population.

  7. Neurostimulation for primary headache disorders: Part 2, review of central neurostimulators for primary headache, overall therapeutic efficacy, safety, cost, patient selection, and future research in headache neuromodulation.

    Science.gov (United States)

    Jenkins, Brian; Tepper, Stewart J

    2011-10-01

    This article is the second of 2 articles reviewing neurostimulation for primary headaches. In Part 1, we described methods, pathophysiology and anatomy, and history of neuromodulation in the treatment of headache, as well as reviewing the literature on peripheral neuromodulation for primary headaches. Peripheral targets for stimulation include percutaneous nerves, transcranial holocephalic, occipital nerves, auriculotemporal nerves, supraorbital nerves, cervical epidural, and sphenopalatine ganglia. In Part 2, we describe available literature on central neuromodulation in primary headaches. Central stimulation targets include vagus nerve and deep brain structures. Part 2 also analyzes overall therapeutic efficacy, safety, cost, patient selection, and recommendations for further research of neurostimulation modalities based on available data.

  8. Novel insights in the faecal egg count reduction test for monitoring drug efficacy against gastrointestinal nematodes of veterinary importance.

    Science.gov (United States)

    Levecke, B; Dobson, R J; Speybroeck, N; Vercruysse, J; Charlier, J

    2012-09-10

    The faecal egg count reduction test (FECRT) is the method of choice to monitor anthelmintic efficacy against gastro-intestinal nematodes in livestock. Guidelines on how to conduct a FECRT are made available by the World Association for the Advancement of Veterinary Parasitology (WAAVP). Since the publication of these guidelines in the early 1990 s, some limitations have been noted, including (i) the ignorance of host-parasite interactions that depend on animal and parasite species, (ii) their feasibility under field conditions, (iii) appropriateness of study design, and (iv) the high detection limit of the recommended faecal egg count (FEC) method. Therefore, the objective of the present study was to empirically assess the impact of the level of excretion and aggregation of FEC, sample size and detection limit of the FEC method on the sensitivity and specificity of the FECRT to detect reduced efficacy (<90% or <95%) and to develop recommendations for surveys on anthelmintic resistance. A simulation study was performed in which the FECRT (based on the arithmetic mean of grouped FEC of the same animals before and after drug administration) was conducted under varying conditions of mean FEC, aggregation of FEC (inversely correlated with k), sample size, detection limit and 'true' drug efficacies. Classification trees were built to explore the impact of the above factors on the sensitivity and specificity of detecting a truly reduced efficacy. For a reduced-efficacy threshold of 90%, most combinations resulted in a reliable detection of reduced and normal efficacy. For the reduced-efficacy threshold of 95% however, unreliable FECRT results were found when sample sizes <15 were combined with highly aggregated FEC (k=0.25) and detection limits ≥ 5 EPG or when combined with detection limits ≥ 15 EPG. Overall, an increase in sample size and mean preDA FEC, and a decrease in detection limit improved the diagnostic accuracy. FECRT remained inconclusive under any

  9. Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

    Directory of Open Access Journals (Sweden)

    Yuya Yoshimoto

    Full Text Available PURPOSE: There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL activity. METHODS AND MATERIALS: C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD was defined as the time (in days for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days and prolonged median survival time (MST to 59 days (versus 28 days in the non-irradiated group. CD8(+ cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days. Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days, while anti-FR4 and anti-GITR antibodies did not affect efficacy. CONCLUSIONS: Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4

  10. Effect of b value on monitoring therapeutic response by diffusion-weighted imaging

    Institute of Scientific and Technical Information of China (English)

    Zhao-Xia Jiang; Wei-Jun Peng; Wen-Tao Li; Feng Tang; Shi-Yuan Liu; Xu-Dong Qu; Jian-Hua Wang; Hong-Feng Lu

    2008-01-01

    AIM: To explore the diffusion gradient b-factor that optimizes both apparent diffusion coefficient (ADC) measurement and contrast-to-noise (CNR) for assessing tumor response to transarterial chemoembolization (TACE) in a rabbit model. METHODS: Twelve New Zealand white rabbits bearing VX2 tumors in the liver were treated withT ACE. Diffusion-weighted imaging (DWI) with various b values was performed using the same protocol before and 3 d after treatment with TACE. ADC values and CNR of each tumor pre- and post-treatment with different b factors were analyzed. Correlation between ADC values and extent of necrosis in histological specimens was analyzed by a Pearson's correlation test.RESULTS: The quality of diffusion-weighted images diminished as the b value increased. A substantial decrease in the mean lesion-to-liver CNR was observed on both pre- and post-treatment DW images, the largest difference in CNR pre- and post-treatment was manifested at a b value of 1000 s/mm2 (P = 0.036 ). The effect of therapy on diffusion early after treatment was shown by a significant increase in ADCs (P= 0.007), especially with large b factors (≥ 600 s/mm2). The mean percentage of necrotic cells present within the tumor was 76.3%-97.5%. A significant positive correlation was found between ADC values and the extent of necrosis with all b values except for b200, a higher relative coefficient between ADC values and percentage of necrosis was found on DWI with bl000 and b2000 (P=0.002 and 0.006, respectively).CONCLUSION: An increasing b value of up to 600 s/mm2 would increase ADC contrast pre-and post-treatment, but decrease image quality. Taking into account both CNR and ADC measurement, diffusion-weighted imaging obtained with a b value of 1000 s/mm2 is recommended for monitoring early hepatic tumor response to TACE.

  11. American Gastroenterological Association Institute Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Diseases.

    Science.gov (United States)

    Vande Casteele, Niels; Herfarth, Hans; Katz, Jeffry; Falck-Ytter, Yngve; Singh, Siddharth

    2017-09-01

    Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease. To inform these clinical guidelines, this technical review was developed in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework for interventional and prognostic studies, and focused on the application of TDM for biologic therapy, specifically anti-tumor necrosis factor-α agents, and for thiopurines. Focused questions address the benefits and risks of a strategy of reactive TDM (in patients with active inflammatory bowel disease) to guide treatment changes compared with empiric treatment changes, and the benefits and risks of a strategy of routine proactive TDM (during routine clinical care in patients with quiescent disease) compared with no routine TDM. Additionally, the review addresses the benefits and risks of routine measurement of thiopurine methyltransferase enzyme activity or genotype before starting thiopurine therapy compared with empiric weight-based dosing and explores the performance of different trough drug concentrations for anti-tumor necrosis factor agents and thiopurines to inform clinical decision making when applying TDM in a reactive setting. Due to a paucity of data, this review does not address the role of TDM for more recently approved biologic agents, such as vedolizumab or ustekinumab. Copyright © 2017 AGA Institute. Published by Elsevier

  12. Therapeutic drug monitoring of piperacillin-tazobactam using spent dialysate effluent in patients receiving continuous venovenous hemodialysis.

    Science.gov (United States)

    Connor, Michael J; Salem, Charbel; Bauer, Seth R; Hofmann, Christina L; Groszek, Joseph; Butler, Robert; Rehm, Susan J; Fissell, William H

    2011-02-01

    Sepsis and multisystem organ failure are common diagnoses affecting nearly three-quarters of a million Americans annually. Infection is the leading cause of death in acute kidney injury, and the majority of critically ill patients who receive continuous dialysis also receive antibiotics. Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics. Our research group directed its attention toward antibiotic dosing strategies in patients with acute renal failure (ARF), and we sought data confirming that patients receiving continuous dialysis and antibiotics actually were achieving therapeutic plasma drug levels during treatment. In the course of those investigations, we explored "fast-track" strategies to estimate plasma drug concentrations. As most antimicrobial antibiotics are small molecules and should pass freely through modern high-flux hemodialyzer filters, we hypothesized that continuous renal replacement therapy (CRRT) effluent could be used as the medium for drug concentration measurement by reverse-phase high-pressure liquid chromatography (HPLC). Here we present the first data demonstrating this approach for piperacillin-tazobactam. Paired blood and dialysate trough-peak-trough samples were drawn from 19 patients receiving piperacillin-tazobactam and continuous venovenous hemodialysis (CVVHD). Total, free, and dialysate drug concentrations were measured by HPLC. Dialysate drug levels predicted plasma free drug levels well (r(2) = 0.91 and 0.92 for piperacillin and tazobactam, respectively) in all patients. These data suggest a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.

  13. ANRIL lncRNA triggers efficient therapeutic efficacy by reprogramming the aberrant INK4-hub in melanoma.

    Science.gov (United States)

    Xu, Shiqiong; Wang, Huixue; Pan, Hui; Shi, Yingyun; Li, Tianyuan; Ge, Shengfang; Jia, Renbing; Zhang, He; Fan, Xianqun

    2016-10-10

    Melanoma is an extremely aggressive disease with rapid progression, high metastatic potential and recurrence. Simultaneous correction of multiple tumor-specific gene abnormalities has become an attractive approach for developing therapeutics to treat melanoma. To potentiate anti-melanoma activity, we tested a "domino effect-like" therapeutic approach by uniquely targeting one defect and automatically triggering the endogenous corrections of other defects. Using this strategy, in a suspicious INK4b-ARF-INK4a gene cluster at chromosome 9p21, aberrant INK4a and INK4b defects were simultaneously endogenously auto-corrected after targeting the suppression of abnormal ANRIL lncRNA. In cell culture, this treatment significantly reduced the tumor metastatic capacity and tumor formation compared with absence of treatment. In animals harboring tumor xenografts, this therapeutic approach significantly inhibited tumor growth and reduced the tumor weight. Our results reveal a novel therapeutic strategy that significantly potentiates anti-melanoma efficiency by reprogramming the aberrant INK4-hub. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Quality attributes of recombinant therapeutic proteins: an assessment of impact on safety and efficacy as part of a quality by design development approach.

    Science.gov (United States)

    Eon-Duval, Alex; Broly, Hervé; Gleixner, Ralf

    2012-01-01

    Quality by Design (QbD) is a new approach to the development of recombinant therapeutic protein products that promotes a better understanding of the product and its manufacturing process. The first step in the QbD approach consists in identifying the critical quality attributes (CQA), i.e., those quality attributes of the product that have an impact on its clinical efficacy or safety. CQAs are identified through a science-based risk assessment taking into consideration a combination of clinical and nonclinical data obtained with the molecule or other similar molecules or platform products, as well as the published literature. The purpose of this article is to perform a comprehensive review of the published literature, supporting an assessment of the impact on safety and efficacy of the quality attributes commonly encountered in recombinant therapeutic proteins, more specifically those produced in mammalian cell expression systems. Quality attributes generally observed in biopharmaceutical proteins including product-related impurities and substances, process-related impurities, product attributes, and contaminants are evaluated one by one for their impact on biological activity, pharmacokinetics and pharmacodynamics, immunogenicity, and overall safety/toxicity.

  15. Transposon-mediated Generation of Cellular and Mouse Models of Splicing Mutations to Assess the Efficacy of snRNA-based Therapeutics

    Directory of Open Access Journals (Sweden)

    Elena Barbon

    2016-01-01

    Full Text Available Disease-causing splicing mutations can be rescued by variants of the U1 small nuclear RNA (U1snRNAs. However, the evaluation of the efficacy and safety of modified U1snRNAs as therapeutic tools is limited by the availability of cellular and animal models specific for a given mutation. Hence, we exploited the hyperactive Sleeping Beauty transposon system (SB100X to integrate human factor IX (hFIX minigenes into genomic DNA in vitro and in vivo. We generated stable HEK293 cell lines and C57BL/6 mice harboring splicing-competent hFIX minigenes either wild type (SChFIX-wt or mutated (SChFIXex5-2C. In both models the SChFIXex5-2C variant, found in patients affected by Hemophilia B, displayed an aberrant splicing pattern characterized by exon 5 skipping. This allowed us to test, for the first time in a genomic DNA context, the efficacy of the snRNA U1-fix9, delivered with an adeno-associated virus (AAV vector. With this approach, we showed rescue of the correct splicing pattern of hFIX mRNA, leading to hFIX protein expression. These data validate the SB100X as a versatile tool to quickly generate models of human genetic mutations, to study their effect in a stable DNA context and to assess mutation-targeted therapeutic strategies.

  16. Transposon-mediated Generation of Cellular and Mouse Models of Splicing Mutations to Assess the Efficacy of snRNA-based Therapeutics.

    Science.gov (United States)

    Barbon, Elena; Ferrarese, Mattia; van Wittenberghe, Laetitia; Sanatine, Peggy; Ronzitti, Giuseppe; Collaud, Fanny; Colella, Pasqualina; Pinotti, Mirko; Mingozzi, Federico

    2016-11-29

    Disease-causing splicing mutations can be rescued by variants of the U1 small nuclear RNA (U1snRNAs). However, the evaluation of the efficacy and safety of modified U1snRNAs as therapeutic tools is limited by the availability of cellular and animal models specific for a given mutation. Hence, we exploited the hyperactive Sleeping Beauty transposon system (SB100X) to integrate human factor IX (hFIX) minigenes into genomic DNA in vitro and in vivo. We generated stable HEK293 cell lines and C57BL/6 mice harboring splicing-competent hFIX minigenes either wild type (SChFIX-wt) or mutated (SChFIXex5-2C). In both models the SChFIXex5-2C variant, found in patients affected by Hemophilia B, displayed an aberrant splicing pattern characterized by exon 5 skipping. This allowed us to test, for the first time in a genomic DNA context, the efficacy of the snRNA U1-fix9, delivered with an adeno-associated virus (AAV) vector. With this approach, we showed rescue of the correct splicing pattern of hFIX mRNA, leading to hFIX protein expression. These data validate the SB100X as a versatile tool to quickly generate models of human genetic mutations, to study their effect in a stable DNA context and to assess mutation-targeted therapeutic strategies.

  17. An Analysis of a Novel, Short-Term Therapeutic Psychoeducational Program for Children and Adolescents with Chronic Neurological Illness and Their Parents; Feasibility and Efficacy.

    Science.gov (United States)

    Joo, Bonglim; Lee, Young-Mock; Kim, Heung Dong; Eom, Soyong

    2017-01-01

    The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children (n = 8) and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological comorbidity; children with intellectual impairment were excluded (IQ parents' session content targeted family dynamic and emotional intervention, coping skills, childcare and education, and finishing up, respectively. Clinical psychologists administered psychological assessments (viz., Child Behavior Checklist, Pediatric Quality of Life Inventory, Parenting Stress Index, Beck Depression Inventory, Children's Depression Inventory, and Revised Children's Manifest Anxiety Scale) at pre- and post-intervention, and administered satisfaction surveys following the intervention. Participants' opinions about the program's necessity, contents, and process, and participants' overall program satisfaction were analyzed. Parents and children reported high levels of satisfaction with the program. Externalizing behavioral problems, anxiety/depression, and emotional functioning from quality of life showed improvement after the intervention. Although not statistically significant, total child stress trended downward from pre- to post-intervention. A four-session structured therapeutic psycho-educational program for children and adolescents with chronic neurological illness and their parents was successfully implemented, showing good compliance and high satisfaction and efficacy.

  18. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction

    Directory of Open Access Journals (Sweden)

    Xiaodong Xue

    2015-01-01

    Full Text Available Objectives. Low survival rate of mesenchymal stem cells (MSCs severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI. Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs or empty vector (vector-MSCs. MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF, insulin-like growth factor-1 (IGF-1, and plate-derived growth factor (PDGF increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  19. [Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens].

    Science.gov (United States)

    Wang, Fan; Yuan, Hai-Long; Duan, Xian-Lin; Wang, Lei; Cao, Hai-Zhou; Xu, Jian-Li; Qu, Jian-Hua

    2014-08-01

    This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P DA group [(0.21 ± 0.16)×10(9)/L] (P DA group (9.17 ± 7.04)d (P DA group (21.45 months) (P DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.

  20. Therapeutic drug monitoring of continuous-infusion acylovir for disseminated herpes simplex virus infection in a neonate receiving concurrent extracorporeal life support and continuous renal replacement therapy.

    Science.gov (United States)

    Cies, Jeffrey J; Moore, Wayne S; Miller, Kyle; Small, Christine; Carella, Dominick; Conley, Susan; Parker, Jason; Shea, Paul; Chopra, Arun

    2015-02-01

    Disseminated herpes simplex virus (HSV) infection in neonates represents a devastating entity that yields high mortality. Acyclovir is the primary antiviral agent used to treat life-threatening HSV infections in neonates; however, even though the agent has reduced morbidity overall from these infections, mortality with disseminated disease remains high. Currently, to our knowledge, no data exist regarding therapeutic drug monitoring of acyclovir in the setting of extracorporeal life support (ECLS) or continuous renal replacement therapy (CRRT) coupled with ECLS. We describe the case of a 14-day-old female with disseminated HSV-1 infection that progressed to fulminant hepatic and renal failure, necessitating the use of ECLS for hemodynamic support and CRRT as a treatment modality for hepatic and renal failure. The standard dosage of acyclovir 20 mg/kg/dose intravenously every 8 hours had been initiated, but after conversion to ECLS and CRRT, the patient's dosage was increased to 30 mg/kg/dose every 8 hours. After a repeat viral load remained unchanged from the initial viral load at 1 × 10(8)  copies/ml, the patient was transitioned from intermittent dosing to a continuous infusion of acyclovir added to the dialysate solution for CRRT at a concentration of 5.5 mg/L. To provide an optimal outcome, dosing was designed to maintain acyclovir plasma concentrations of at least 3 mg/L in order to maintain an acyclovir concentration of at least 1 mg/L in the cerebrospinal fluid. The patient's acyclovir serum concentrations measured at 24 and 72 hours after starting continuous-infusion acyclovir via the dialysate were 8.8 and 5.3 mg/L, respectively, allowing for a continuous serum concentration above 3 mg/L. Unfortunately, before a repeat viral load could be obtained to assess the efficacy of the continuous infusion acyclovir, the patient experienced an intracerebral hemorrhage as a complication related to ECLS after which technological support was withdrawn

  1. Glycolipid antigens for treating hepatic colorectal cancer metastases and their effect on the therapeutic efficacy of live attenuated Listeria monocytogenes.

    Science.gov (United States)

    Olino, Kelly; Edil, Barish H; Meckel, Kristen F; Pan, Xiaoyu; Thuluvath, Avesh; Pardoll, Drew M; Schulick, Richard D; Yoshimura, Kiyoshi; Weber, Walter P

    2012-05-01

    Previous work demonstrated that a subset of natural killer T cells in mice decreased the antitumor efficacy of live attenuated Listeria monocytogenes where the actin A and internalin B genes were genetically deleted (LMD) against murine hepatic colorectal cancer metastases. Therefore, we hypothesized that the use of specific glycolipids known to selectively stimulate natural killer T-cell subsets used alone or co-administered with LMD would increase survival. We found that early or multiple administrations of glycolipids after tumor challenge had a strong impact on survival with or without LMD. Solitary administration or treatment given later was less efficacious but still showed a strong trend toward enhancing the antitumor activity of LMD. These results underscore the potential of glycolipids in the treatment of hepatic metastases and encourage further investigations into the immunomodulation of natural killer T cells to enhance the antitumor activity of LMD.

  2. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Bartelink, Imke H.; Bredius, Robbert G. M.; Ververs, Tessa T.; Raphael, Martine F.; van Kesteren, Charlotte; Bierings, Marc; Rademaker, Carin M. A.; den Hartigh, J.; Uiterwaal, Cuno S. P. M.; Zwaveling, Juliette; Boelens, Jaap J.

    2008-01-01

    Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). Th

  3. Total Laparoscopic Radical Hysterectomy for Treatment of Uterine Malignant Tumors:Analysis of Short-term Therapeutic Efficacy

    Institute of Scientific and Technical Information of China (English)

    沈怡; 王泽华

    2010-01-01

    To investigate the efficacy and the clinical value of total laparoscopic radical hysterectomy(TLRH) for the treatment of uterine malignancies,we performed a retrospective review of 87 patients with cervical cancer and 23 patients with endometrial carcinoma who underwent TLRH at Union hospital between June 2008 and September 2009.Data collected included operative time,estimated blood loss,lymph node count,time for the recovery of normal temperature and time to resumption of normal bladder function,intraopera...

  4. Therapeutic efficacy of digital music gastric electrical pacing for refractory functional dyspepsia concomitant with non-erosive reflux disease

    Directory of Open Access Journals (Sweden)

    Ya-mei RAN

    2015-04-01

    Full Text Available Objective To study the clinical efficacy of digital music gastric electrical pacing for refractory functional dyspepsia concomitant with non-erosive reflux disease, and its effects on mental health and life-quality of the patients. Methods According to the Rome Ⅲ criteria and Montreal consensus in diagnosis of gastroesophageal reflux disease, 50 patients with concomitant refractory functional dyspepsia and non-erosive reflux disease were recruited. The clinical efficacy of digital music gastric electrical pacing were evaluated using the score of clinical symptoms before treatment and 15 days after treatment, and the mental health and life-quality of patients were assessed using symptom checklist 90. Results Main symptoms, including upper abdominal pain, abdominal fullness, early satiety, belching, hiccup, nausea, heartburn, acid reflux (daytime, nocturnal acid reflux, loss of appetite and sleep, were significantly improved 15 days after treatment compared with those of pre-treatment, and there were statistically significant differences (all P<0.005. The significant response rate/response rate (efficacy rate were 59.0%/100.0%, 59.3%/96.3%, 47.0%/94.1%, 61.3%/96.8 %, 86.7%/100.0%, 80.0%/100.0%, 64.3%/92.9%, 73.7%/89.5%, 64.3%/85.7%, 90.0%/90.0%, 36.7%/93.3% respectively. After treatment for 15 days, the overall response rate of symptom relief was 94.4% in patients and the overall significant response rate was 65.7%. The symptom scores of somatization, obsessive-compulsiveness, depression, and anxiety were significantly improved, and the differences were statistically significant (all P<0.01. Conclusion The clinical efficacy of digital music gastric electrical pacing is significant for refractory functional dyspepsia concomitant with nonerosive reflux disease, and it is expected to be a new option for the treatment of this disease complex. DOI: 10.11855/j.issn.0577-7402.2015.03.08

  5. THERAPEUTIC EFFICACY OF PROBIOTICS AND SHORT CHAIN FATTY ACIDS IN GASTROINTESTINAL DISEASE: EVALUATION OF METABOLIC, HORMONAL AND INFLAMMATORY PARAMETERS

    OpenAIRE

    2014-01-01

    In these three years we studied probiotics and postbiotics efficacy and their mechanism/s in preventing or limiting gastrointestinal diseases, such as hepatic steatosis and ulcerative colitis. On the basis of strength anatomical correlation between liver and gut, we wanted to observe if microorganisms present in gut and their postbiotic derivatives, the short chain fatty acids, were able to prevent or cure not only local intestinal disease but also to limit extraintestinal and systemic pathol...

  6. The therapeutic efficacy of erdosteine in the treatment of chronic obstructive bronchitis: A meta-analysis of individual patient data

    OpenAIRE

    M. Cazzola; Floriani, I.; Page, C. P.

    2010-01-01

    Abstract Aim to test the available evidence for the efficacy of erdosteine in adults with stable or exacerbated CB/COPD. Erdosteine, a drug approved for the treatment of acute and chronic pulmonary diseases, has been shown to be an effective treatment for chronic bronchitis or COPD (CB/COPD) in several studies, although marked differences in the perception of its usefulness still remain. Methods meta-analysis of individual patient data fr...

  7. The efficacy of miRNA122, a novel therapeutic target, for predicting the progression of hepatocellular carcinoma (HCC)

    Institute of Scientific and Technical Information of China (English)

    Lifeng Wang; Zheng Zhang; Fu-Sheng Wang

    2012-01-01

    Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide,and it accounts for 85-90% of all primary liver cancers.Owing to the limited therapeutic options available,the 5-year survival rate remains relatively low for patients with HCC.The development of HCC is a multistage process1 that involves changes in the expression of multiple oncogenes,tumor suppressor genes and microRNAs that are involved in the cell cycle,as well as in cell growth,apoptosis,migration and tumor metastasis.2,3 Finding an accurate biomarker that can predict HCC progression is important for clinicians to be able to determine the optimal therapeutic strategy.

  8. Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients.

    Science.gov (United States)

    McCune, Jeannine S; Baker, K Scott; Blough, David K; Gamis, Alan; Bemer, Meagan J; Kelton-Rehkopf, Megan C; Winter, Laura; Barrett, Jeffrey S

    2013-03-01

    Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors- group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children.

  9. Electrochemical monitoring-on-chip (E-MoC) of HIV-infection in presence of cocaine and therapeutics.

    Science.gov (United States)

    Kaushik, Ajeet; Vabbina, Phani Kiran; Atluri, Venkata; Shah, Pratikkumar; Vashist, Arti; Jayant, Rahul Dev; Yandart, Adriana; Nair, Madhavan

    2016-12-15

    Electrochemical monitoring-on-chip (E-MoC)-based approach for rapid assessment of human immunodeficiency virus (HIV)-infection in the presence of cocaine (Coc) and specific drugs namely i.e., tenofovir (Tef), rimcazole (RA) is demonstrated here, for the first time, using electrochemical impedance spectroscopy (EIS). An in-vitro primary human astrocytes (HA) model was developed using a cultureware chip (CC, used for E-MoC) for HIV-infection, Coc exposure and treatment with anti-HIV drug i.e., Tef, and Coc antagonist i.e., RA. The charge transfer resistance (Rct) value of each CC well varies with respect to infection and treatment demonstrated highly responsive sensitivity of developed chip. The results of E-MoC, a proof-of-the concept, suggested that HIV-infection progression due to Coc ingestion and therapeutic effects of highly specific drugs are measurable on the basis of cell electrophysiology. Though, this work needs various molecular biology-based optimizations to promote this technology as an analytical tool for the rapid assessment of HIV-infection in a patient to manage HIV diseases for timely diagnosis. The presented study is based on using CNS cells and efforts are being made to perform this method using peripheral cells such as monocytes derived dendritic cells.

  10. Therapeutic Efficacy Assessment of CK6, a Monoclonal KIT Antibody, in a Panel of Gastrointestinal Stromal Tumor Xenograft Models

    Directory of Open Access Journals (Sweden)

    Thomas Van Looy

    2015-04-01

    Full Text Available We evaluated the efficacy of CK6, a KIT monoclonal antibody, in a panel of human gastrointestinal stromal tumor (GIST xenograft models. Nude mice were bilaterally transplanted with human GIST xenografts (four patient derived and two cell line derived, treated for 3 weeks, and grouped as follows: control (untreated; CK6 (40 mg/kg, 3× weekly; imatinib (50 mg/kg, twice daily; sunitinib (40 mg/kg, once daily; imatinib + CK6; sunitinib + CK6 (same doses and schedules as in the single-agent treatments. Tumor volume assessment, Western blot analysis, and histopathology were used for evaluation of efficacy. Statistical analysis was performed using Mann-Whitney U (MWU and Wilcoxon matched-pairs tests. CK6 as a single agent only reduced tumor growth rate in the UZLX-GIST3 model (P = .053, MWU compared to control, while in none of the other GIST models an effect on tumor growth rate was observed. CK6 did not result in significant anti-proliferative or pro-apoptotic effects in any of the GIST models, and moreover, CK6 did not induce a remarkable inhibition of KIT activation. Furthermore, no synergistic effect of combining CK6 with tyrosine kinase inhibitors (TKIs was observed. Conversely, in certain GIST xenografts, anti-tumor effects seemed to be inferior under combination treatment compared to single-agent TKI treatment. In the GIST xenografts tested, the anti-tumor efficacy of CK6 was limited. No synergy was observed on combination of CK6 with TKIs in these GIST models. Our findings highlight the importance of using relevant in vivo human tumor xenograft models in the preclinical assessment of drug combination strategies.

  11. Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction

    Directory of Open Access Journals (Sweden)

    Sang-oh Han

    2017-03-01

    Full Text Available Pompe disease results from acid α-glucosidase (GAA deficiency, and enzyme replacement therapy (ERT with recombinant human (rh GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV vector containing a liver-specific promoter. GAA knockout (KO mice were administered either a weekly injection of rhGAA (20 mg/kg or a single injection of AAV2/8-LSPhGAA (8 × 1011 vector genomes [vg]/kg. Both treatments significantly reduced glycogen content of the heart and diaphragm. Although ERT triggered anti-GAA antibody formation, there was no detectable antibody response following AAV vector administration. The efficacy of three lower dosages of AAV2/8-LSPhGAA was evaluated in GAA-KO mice, either alone or in combination with ERT. The minimum effective dose (MED identified was 8 × 1010 vg/kg to reduce glycogen content in the heart and diaphragm of GAA-KO mice. A 3-fold higher dose was required to suppress antibody responses to ERT. Efficacy from liver gene therapy was slightly greater in male mice than in female mice. Vector dose correlated inversely with anti-GAA antibody formation, whereas higher vector doses suppressed previously formed anti-GAA antibodies as late as 25 weeks after the start of ERT and achieved biochemical correction of glycogen accumulation. In conclusion, we identified the MED for effective AAV2/8-LSPhGAA-mediated tolerogenic gene therapy in Pompe disease mice.

  12. Therapeutic efficacy of Wuzhi tablet (Schisandra sphenanthera Extract) on acetaminophen-induced hepatotoxicity through a mechanism distinct from N-acetylcysteine.

    Science.gov (United States)

    Fan, Xiaomei; Chen, Pan; Jiang, Yiming; Wang, Ying; Tan, Huasen; Zeng, Hang; Wang, Yongtao; Qu, Aijuan; Gonzalez, Frank J; Huang, Min; Bi, Huichang

    2015-03-01

    Acetaminophen (APAP) hepatotoxicity is the most common cause of drug-induced liver injury and N-acetylcysteine (NAC) is the primary antidote of APAP poisoning. Wuzhi tablet (WZ), the active constituents well identified and quantified, is a preparation of an ethanol extract of Schisandra sphenanthera and exerts a protective effect toward APAP-induced hepatotoxicity in mice. However, the clinical use of WZ to rescue APAP-induced acute liver injury and the mechanisms involved in the therapeutic effect of WZ remain unclear. Therefore, the effect of WZ on APAP hepatotoxicity was compared with NAC in mice, and molecular pathways contributing to its therapeutic action were investigated. Administration of WZ 4 hours after APAP treatment significantly attenuated APAP hepatotoxicity and exerted much better therapeutic effect than NAC, as revealed by morphologic, histologic, and biochemical assessments. Both WZ and NAC prevented APAP-induced c-Jun N-terminal protein kinase activation and mitochondrial glutathione depletion in livers. The protein expression of nuclear factor erythroid 2-related factor 2 target genes including Gclc, Gclm, Ho-1, and Nqo1 was increased by WZ administration. Furthermore, p53 and p21 levels were upregulated upon APAP exposure, which were completely reversed by postdosing of WZ 4 hours after APAP treatment over 48 hours. In comparison with NAC, WZ significantly increased the expression of cyclin D1, cyclin D-dependent kinase 4, proliferating cell nuclear antigen, and augmenter of liver regeneration in APAP-injured livers. This study demonstrated that WZ possessed a therapeutic efficacy against APAP-induced liver injury by inhibiting oxidative stress and stimulating a regenerative response after liver injury. Thus WZ may represent a new therapy for APAP-induced acute liver injury.

  13. Are ex vivo neutralising antibodies against IFN-beta always detrimental to therapeutic efficacy in multiple sclerosis?

    DEFF Research Database (Denmark)

    Sorensen, P S; Koch-Henriksen, Nils; Bendtzen, K

    2007-01-01

    Neutralising antibodies (NAbs) against interferon (IFN)-beta reduce the treatment effect in multiple sclerosis (MS). However, data from pivotal trials of IFN-beta in MS suggest that NAb-positive patients may have a reduced relapse rate during the first six to 12 months of therapy. We collected...... rates during the first six or 12 months of therapy. We hypothesise that low affinity NAbs, present early after the start of IFN-beta therapy, though neutralising in vitro in sensitive assays increase the half-life of IFN-beta in vivo and, thereby, enhance the therapeutic effect. With affinity maturation...

  14. EVALUATION OF THE THERAPEUTIC EFFICACY OF HIGH-INTENSITY PULSED-PERIODIC LASER RADIATION (CLINICAL AND EXPERIMENTAL OBSERVATIONS)

    OpenAIRE

    2016-01-01

    From the experience of clinical observations, we have shown a high therapeutic effectiveness of the medical laser KULON-MED in: cosmetics, non-cancer inflammatory diseases of the gastrointestinal tract and cancer (cancer of the stomach and colon) as at different wavelengths, and with different types of photosensitizers. In the area of anti-tumor photodynamic therapy (PDT), based on experimental studies, we have showed the high antitumor (sarcoma S‑37) effectiveness of the laser (with the inhi...

  15. Julia Butler Hansen NWR: Initial Survey Instructions for Columbian White-tailed Deer FLIR Efficacy Monitoring

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Recovery of the lower Columbia population of Columbian White-tailed Deer (CWTD) relies on specific population goals. As such, monitoring programs cannot be based on...

  16. Sonic Hedgehog Controls the Phenotypic Fate and Therapeutic Efficacy of Grafted Neural Precursor Cells in a Model of Nigrostriatal Neurodegeneration.

    Science.gov (United States)

    Madhavan, Lalitha; Daley, Brian F; Davidson, Beverly L; Boudreau, Ryan L; Lipton, Jack W; Cole-Strauss, Allyson; Steece-Collier, Kathy; Collier, Timothy J

    2015-01-01

    The expression of soluble growth and survival promoting factors by neural precursor cells (NPCs) is suggested to be a prominent mechanism underlying the protective and regenerative effects of these cells after transplantation. Nevertheless, how and to what extent specific NPC-expressed factors contribute to therapeutic effects is not well understood. Using RNA silencing, the current study investigated the roles of two donor NPC molecules, namely glial cell-line derived neurotrophic factor (GDNF) and sonic hedgehog (SHH), in the protection of substantia nigra dopamine neurons in rats treated with 6-hydroxydopamine (6-OHDA). Analyses indicate that as opposed to the knock-down of GDNF, SHH inhibition caused a profound decline in nigrostriatal neuroprotection. Further, SHH silencing also curbed endogenous neurogenesis and the migration of host brdU+/dcx+ neural precursors into the striatum, which was present in the animals receiving control or GDNF silenced NPCs. A change in graft phenotype, mainly reflected by a reduced proportion of undifferentiated nestin+ cells, as well as a significantly greater host microglial activity, suggested an important role for these processes in the attenuation of neuroprotection and neurogenesis upon SHH silencing. Overall these studies reveal core mechanisms fundamental to grafted NPC-based therapeutic effects, and delineate the particular contributions of two graft-expressed molecules, SHH and GDNF, in mediating midbrain dopamine neuron protection, and host plasticity after NPC transplantation.

  17. RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.

    Science.gov (United States)

    Park, Seung-Hwan; Zheng, Jin Hai; Nguyen, Vu Hong; Jiang, Sheng-Nan; Kim, Dong-Yeon; Szardenings, Michael; Min, Jung Hyun; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

    2016-01-01

    Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect.

  18. Therapeutic Drug Monitoring and Pharmacogenomics%治疗药物监测与药物基因组学

    Institute of Scientific and Technical Information of China (English)

    鲍红荣; 赵志刚

    2011-01-01

    目的 将药物基因组学应用到临床合理用药,为临床个体化给药提供依据.方法 查阅文献,总结治疗药物监测在临床实践中发现的问题,并阐述药物基因组学等学科的发展与特点.结果 基因多态性是药物治疗效果因人而异的最重要因素.通过药物基因组学研究,实现临床个体化药物治疗,是治疗药物浓度监测的进一步延伸和充实.药物基因组学应用到临床合理用药,弥补了以往只根据血药浓度进行个体化给药的不足,也为以前无法解释的药效学现象找到了答案.结论 将来的临床药物治疗模式应以遗传药理学、药物基因组学为导向,结合血药浓度监测,来指导特定药物对特定患者的合理使用.%Objective To apply pharmacogenomics in clinical rational drug use to provide the basis for clinical individualized medication.Methods Through retrieving literatures, the problems found in clinical practice of therapeutic drug monitoring (TDM) were summarized, and the development and characteristics of pharmacogenomics were elaborated. Results The gene polymorphism is the most important factor that the medication effects vary from person to person. Through pharmacogenomics studies, realizing the individualized treatment is further extension and enrichment of TDM. Application of pharmacogenomics to clinical rational drug use remedies the shortage of previous individualized medication only according to drug concentration and also finds the answer to the phenomenon of pharmacedynamics can not being explained before, which opens up a new way for clinical personalized medication. Conclusion Future clinical pharmacotherapy model should be oriented with genetic pharmacology and pharmacogenomics, combined with blood drug concentration monitoring, and guide the rational use of particular drugs to patients.

  19. Hypokalaemia: Improving the investigation, management and therapeutic monitoring of hypokalaemic medical inpatients at a district general hospital.

    Science.gov (United States)

    Jordan, Mark; Caesar, Jenny

    2015-01-01

    Hypokalaemia is prevalent in 20% of hospitalised patients. Furthermore, inadequate management of hypokalemia was identified in 24% of these patients. Associated with significant patient morbidity and mortality, the identification, investigation, and treatment of hypokalaemia was identified as an area for improvement in the management of medical inpatients. The project aims to measure the assessment, management, and therapeutic monitoring of medical inpatients with hypokalaemia in a district general hospital. All medical inpatients over a one week period who met the criteria for hypokalaemia (serum potassium <3.5 mmol/L on standard biochemical sample) were included in the audit. Patient's notes were located and evaluated to identify if they had mild, moderate, or severe hypokalaemia. Further data on ECG requests, repeat U&Es, serum magnesium analysis, treatment prescribed, and medication review dates was collated. A re-audit was completed after the introduction of a set of interventions which included a hypokalaemia treatment algorithm. Pre-intervention analysis of all medical inpatients, who met our inclusion criteria for hypokalaemia, identified 32 patients. 25 of these patients met the criteria for mild hypokalaemia (3.1-3.4 mmol/L) and 7 met the criteria for moderate hypokalaemia (2.5-3.0 mmol/L). Only 7/32 (22 %) patients were receiving adequate treatment based on trust guidelines. Post intervention results showed marked improvement in the management of patients with hypokalaemia. A total of 30 patients were identified in this post-intervention group. There were 16/30 patients who qualified as mild hypokalaemia (3.1-3.4 mmol/L) and 14/30 with moderate hypokalaemia (2.5-3.0 mmol/L). 19/30 (63%) patients in the post-intervention group were correctly prescribed appropriate medication doses consistent with the treatment algorithm. Following the initial success of the project, analysis at 3 months showed a positive trend for sustained improvement when compared to

  20. Plasma quetiapine in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 2000–2011

    Science.gov (United States)

    Bowskill, Sally V.J.; Patel, Maxine X.; Flanagan, Robert J.

    2013-01-01

    Objective: Suggested predose plasma quetiapine target ranges for effective therapy in schizophrenia lie between 50 and 500 µg/l. We aimed to examine data from a quetiapine therapeutic drug monitoring (TDM) service to assess the plasma quetiapine concentrations attained at specified doses in clinical practice. Method: We studied TDM data from patients given immediate-release quetiapine in the period 2000–2011. Results: There were 946 samples from 487 patients (257 males, age at time of first sample, median [range] 34 [14–87] years, and 230 females, age at time of first sample, median [range] 38 [10–92] years). The plasma quetiapine concentration was <50 and <100 µg/l in 30% and 50% of samples, respectively (no quetiapine detected in 9% of samples). The relationship between dose and plasma quetiapine was poor. The mean (95% confidence interval [CI]) quetiapine dose was higher (t = 3.6, df = 446, p <0.01) in males versus females (641 [600–1240] and 548 [600–943] mg/day, respectively), although there was no difference in median dose (600 mg/day) or in the mean (95% CI) plasma quetiapine concentrations attained. Smoking habit had no discernible effect on plasma quetiapine concentration. Conclusions: There was a poor relationship between dose and plasma quetiapine concentration in this study, as found by others. This is probably because of the short plasma half-life of the drug, at least in part. Nevertheless, quetiapine TDM can help assess adherence and measurement of quetiapine metabolites, notably N-desalkylquetiapine, as well as quetiapine itself may enhance the value of quetiapine TDM in future. PMID:24167685

  1. Outliers on the dose-response curve: how to minimize this problem using therapeutic drug monitoring, an underutilized tool in psychiatry.

    Science.gov (United States)

    Preskorn, Sheldon H

    2010-05-01

    This column continues the discussion of outliers on the dose-response curve begun in earlier columns. It focuses on therapeutic drug monitoring (TDM) as an underutilized tool in psychiatry to minimize this problem. The scientific rationale for dose adjustment based on TDM is presented and its efficiency is contrasted with dose adjustment based on clinical assessment of response. In current practice, the use of TDM with psychiatric drugs is generally restricted to drugs with narrow therapeutic windows or drugs imported into psychiatry from neurology where TDM is more commonly used. Examples of each of these types of drugs are cited.

  2. An Analysis of a Novel, Short-Term Therapeutic Psychoeducational Program for Children and Adolescents with Chronic Neurological Illness and Their Parents; Feasibility and Efficacy

    Directory of Open Access Journals (Sweden)

    Bonglim Joo

    2017-05-01

    Full Text Available The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children (n = 8 and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological comorbidity; children with intellectual impairment were excluded (IQ < 80. The program was carried out weekly for four sessions. In each of the 4 weeks, children's session content addressed self, emotion, coping skills, and finishing up, respectively; and parents' session content targeted family dynamic and emotional intervention, coping skills, childcare and education, and finishing up, respectively. Clinical psychologists administered psychological assessments (viz., Child Behavior Checklist, Pediatric Quality of Life Inventory, Parenting Stress Index, Beck Depression Inventory, Children's Depression Inventory, and Revised Children's Manifest Anxiety Scale at pre- and post-intervention, and administered satisfaction surveys following the intervention. Participants' opinions about the program's necessity, contents, and process, and participants' overall program satisfaction were analyzed. Parents and children reported high levels of satisfaction with the program. Externalizing behavioral problems, anxiety/depression, and emotional functioning from quality of life showed improvement after the intervention. Although not statistically significant, total child stress trended downward from pre- to post-intervention. A four-session structured therapeutic psycho-educational program for children and adolescents with chronic neurological illness and their parents was successfully implemented, showing good compliance and high satisfaction and efficacy.

  3. Therapeutic efficacies of Coriandrum sativum aqueous extract against metronidazole-induced genotoxicity in Channa punctatus peripheral erythrocytes.

    Science.gov (United States)

    Talapatra, Soumendra Nath; Dasgupta, Subham; Guha, Gunjan; Auddy, Moumita; Mukhopadhyay, Aniruddha

    2010-12-01

    Metronidazole (MTZ), a nitroimidazole drug, is primarily used as an anti-protozoan or an anti-bacterial agent in humans, although its genotoxic and carcinogenic effects have been widely reported, particularly in aquatic organisms. MTZ may induce DNA damages through single-strand breaks, modification of bases, DNA-DNA and DNA-protein cross-links, ultimately leading to apoptosis or necrosis. Here, we have assessed the genotoxicity of MTZ in the peripheral erythrocytes of Channa punctatus, using micronucleation (MN) and binucleation (BN) as genotoxicity markers. The therapeutic potential of aqueous extract of Coriandrum sativum against MTZ-induced genotoxicity has also been examined. The results show significant (Psativum leaf extract. Hence, we establish that MTZ can produce considerable degrees of micronucleus and binucleus formation in peripheral erythrocytes of C. punctatus, and such deleterious effect of MTZ treatment can be mitigated by aqueous extract of C. sativum leaves.

  4. The level of telomere dysfunction determines the efficacy of telomerase-based therapeutics in a lung cancer cell line.

    Science.gov (United States)

    Pantic, Milena; Zimmermann, Stefan; Waller, Cornelius F; Martens, Uwe M

    2005-05-01

    Telomerase is the ribonucleoprotein enzyme that maintains telomeres of eukaryotic chromosomes. Activation of telomerase is a common feature of the majority of human cancers, and inhibition of this enzyme has been proposed as a novel target for cancer therapeutics. Here, we investigated the effects of telomerase inhibition in the non-small cell lung cancer cell line NCI-H460, using a genetic approach by ectopic expression of dominant-negative (DN)-hTERT. Five clones were selected in which telomerase activity was completely abolished. As a result, telomere erosion was observed leading to proliferation arrest after a lag period of 20-28 population doublings. Although overall telomere length was similar between the different clones as measured by quantitative fluorescence in situ hybridization (Q-FISH), striking differences were found in telomere length of individual chromosomes. In particular, lack of individual telomeres and formation of end-to-end fusions were variable. Interestingly, this level of individual telomere dysfunction was positively correlated with the remaining life span of the different clones in vitro. In addition, the amount of telomere dysfunction induced by DN-hTERT was twice as high compared to the small molecule telomerase inhibitor BIBR1532, which induced growth arrest after >100 population doublings. Thus, pharmacological strategies that aim at inhibition of telomerase in cancer cells should take into account that not only overall telomere shortening, but rapid induction of a high level telomere dysfunction appears to be the crucial surrogate parameter for the development of future telomerase-based therapeutics.

  5. Histatin 5-spermidine conjugates have enhanced fungicidal activity and efficacy as a topical therapeutic for oral candidiasis.

    Science.gov (United States)

    Tati, Swetha; Li, Rui; Puri, Sumant; Kumar, Rohitashw; Davidow, Peter; Edgerton, Mira

    2014-01-01

    Oropharyngeal candidiasis (OPC) is caused by the opportunistic fungi Candida albicans and is prevalent in immunocompromised patients, individuals with dry mouth, or patients with prolonged antibiotic therapies that reduce oral commensal bacteria. Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. However, Hsts are rapidly degraded in vivo, limiting their usefulness as therapeutic agents despite their lack of toxicity. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54-15), based upon our findings that C. albicans spermidine transporters are required for Hst 5 uptake and fungicidal activity. We found that Hst 54-15-Spd was significantly more effective in killing C. albicans and Candida glabrata than Hst 5 alone in both planktonic and biofilm growth and that Hst 54-15-Spd retained high activity in both serum and saliva. Hst 54-15-Spd was not bactericidal against streptococcal oral commensal bacteria and had no hemolytic activity. We tested the effectiveness of Hst 54-15-Spd in vivo by topical application to tongue surfaces of immunocompromised mice with OPC. Mice treated with Hst 54-15-Spd had significant clearance of candidal tongue lesions macroscopically, which was confirmed by a 3- to 5-log fold reduction of C. albicans colonies recovered from tongue tissues. Hst 54-15-Spd conjugates are a new class of peptide-based drugs with high selectivity for fungi and potential as topical therapeutic agents for oral candidiasis.

  6. Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells.

    Science.gov (United States)

    Prados, Jose; Melguizo, Consolación; Rama, Ana Rosa; Ortiz, Rául; Segura, Ana; Boulaiz, Houria; Vélez, Celia; Caba, Octavio; Ramos, Juan Luís; Aránega, Antonia

    2010-05-01

    The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management of advanced breast cancer. MCF-7 human breast cancer cells were transfected with gef gene using pcDNA3.1-TOPO expression vector. To determine the effect of the combined therapy, MCF-7 transfected and non-transfected cells were exposed to paclitaxel, docetaxel and doxorubicin at different concentrations. The growth-inhibitory effect of gef gene and/or drugs was assessed by MTT assay. Apoptosis modulation was determined by flow cytometric analysis, DNA fragmentation and morphological analysis. Multicellular tumour spheroids (MTS) from MCF-7 cells were used to confirm effectiveness of combined therapy (gef gene and drug). Our results demonstrate that combined therapy gef gene/drugs (paclitaxel, docetaxel or doxurubicin) caused a decrease in cell viability. However, only the gef-doxorubicin (10 microM) combination induced a greater enhancement in the antitumour activity in MCF-7 cells. Most importantly, this combined strategy resulted in a significant synergistic effect, thus allowing lower doses of the drug to be used to achieve the same therapeutic effect. These results were confirmed using MTS in which volume decrease with combined therapy was greater than obtained using the gene therapy or chemotherapy alone, or the sum of both therapies. The cytotoxic effect of gef gene in breast cancer cells enhances the chemotherapeutic effect of doxorubicin. This therapeutic approach has the potential to overcome some of the major limitations of conventional chemotherapy, and may therefore constitute a promising strategy for future

  7. Rapid detection and monitoring therapeutic efficacy of Mycobacterium tuberculosis complex using a novel real-time assay.

    Science.gov (United States)

    Jiang, Li Juan; Wu, Wen Juan; Wu, Hai; Ryang, Son Sik; Zhou, Jian; Wu, Wei; Li, Tao; Guo, Jian; Wang, Hong Hai; Lu, Shui Hua; Li, Yao

    2012-09-01

    We combined real-time RT-PCR and real-time PCR (R/P) assays using a hydrolysis probe to detect Mycobacterium tuberculosis complex (MTBC)-specific 16S rRNA and its rRNA gene (rDNA). The assay was applied to 28 nonrespiratory and 207 respiratory specimens from 218 patients. Total nucleic acids (including RNA and DNA) were extracted from samples, and results were considered positive if the repeat RT-PCR threshold cycle was real-time RT-PCR and real-time PCR load was > or =1.51. The results were compared with those from existing methods, including smear, culture, and real-time PCR. Following resolution of the discrepant results between R/P assay and culture, the overall sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of all samples (including nonrespiratory and respiratory specimens) were 98.2%, 97.2%, 91.7%, and 99.4%, respectively, for R/P assay, and 83.9%, 89.9%, 72.3%, and 94.7%, respectively, for real-time PCR. Furthermore, the R/P assay of four patient samples showed a higher ratio before treatment than after several days of treatment. We conclude that the R/P assay is a rapid and accurate method for direct detection of MTBC, which can distinguish viable and nonviable MTBC, and thus may guide patient therapy and public health decisions.

  8. Original article title: "Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a clinical trial"

    Directory of Open Access Journals (Sweden)

    Omidian Mohammad

    2011-03-01

    Full Text Available Abstract Background Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo. Methods This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid. Results The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively. Conclusion Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo. Trial Registration chiCTRTRC10000930

  9. Predictors of ertapenem therapeutic efficacy in the treatment of urinary tract infections (UTIs) in hospitalized adults: the importance of renal insufficiency and urinary pH.

    Science.gov (United States)

    Cunha, B A; Giuga, J; Gerson, S

    2016-04-01

    In hospitalized adults acute uncomplicated cystitis (AUC) and catheter associated bacteriuria (CAB) may be treated with oral antibiotics. With AUC or CAB due to extended spectrum ß-lactamase (ESBL) + Gram negative bacilli (GNB) physicians often use intravenous therapy, e.g., ertapenem. We reviewed our recent experience in hospitalized adults with AUC and CAB treated with ertapenem. Therapeutic efficacy of ertapenem was assessed by decreased pyuria/bacteriuria, and elimination of the uropathogen. The effectiveness of ertapenem in the presence of renal insufficiency (CrCl 3 days) in patients with decreased renal function and alkaline urinary pH. We reviewed 45 hospitalized adults with AUC or CAB to determine if renal insufficiency and or alkaline urinary pH affected ertapenem efficacy. In the 33 adult hospitalized patients with AUC and 12 with CAB, we found that ertapenem was consistently effective in eliminating the GNB bacteriuria. In hospitalized adults, the presence of renal insufficiency and acid urine, bacteriuria was eliminated in  3 days which has not been previously reported.

  10. Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope.

    Science.gov (United States)

    Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R; Gambhir, Sanjiv S; Kino, Gordon S; Solgaard, Olav; Kaspar, Roger L; Contag, Christopher H

    2010-01-01

    Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

  11. Therapeutic algorithms for the management of sexually transmitted diseases at the peripheral level in Côte d'Ivoire: assessment of efficacy and cost.

    Science.gov (United States)

    La Ruche, G.; Lorougnon, F.; Digbeu, N.

    1995-01-01

    In the acquired immunodeficiency syndrome (AIDS) era, adequate management of sexually transmitted diseases (STDs) is a primary concern in Africa. Assessed in this study is the clinical efficacy and feasibility of WHO-recommended therapeutic algorithms for genital discharges and ulcers, diagnosed without laboratory tests, for use at the primary health care level. Drugs were sold on a cost-recovery basis and included intramuscular ceftriaxone and oral ciprofloxacin for single-dose therapy of gonorrhoea and chancroid. During April 1993 in 10 peripheral health care centres in Abidjan, Côte d'Ivoire, a total of 207 patients were followed up, including 89 cases of male urethritis, 92 cases of vaginal discharges and 26 cases of genital ulcers; clinical success, assessed 7 days after the onset of therapy, was, respectively, 92%, 87%, and 100%. Less than 10% of the 207 patients were referred to the next care level, an acceptable rate from a public health point of view. Medical adherence to the algorithms was excellent for urethral discharges and genital ulcers but poor for vaginal discharges, partly because of intentional therapeutic modifications, without detriment to success. For drugs, the average cost per cure was 1546 francs CFA (US$ 5.60) (maximum, 2980 francs CFA (US$ 10.70). Effective and affordable treatments for STDs are necessary for their realistic case management in Africa. PMID:7614662

  12. Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope

    Science.gov (United States)

    Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R.; Gambhir, Sanjiv S.; Kino, Gordon S.; Solgaard, Olav; Kaspar, Roger L.; Contag, Christopher H.

    2010-05-01

    Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

  13. Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast tumor model.

    Science.gov (United States)

    Şalva, Emine; Turan, Suna O; Kabasakal, Levent; Alan, Saadet; Özkan, Naziye; Eren, Fatih; Akbuğa, Jülide

    2014-03-01

    Angiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer.

  14. Effect of selective and non-selective serotonin receptor activation on L-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats.

    Science.gov (United States)

    Tronci, E; Fidalgo, C; Stancampiano, R; Carta, M

    2015-10-01

    Selective activation of 5-HT1 receptors has been shown to produce near to full suppression of L-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease; however, a reduction of the therapeutic effect of L-DOPA has been reported in several studies. Conversely, we recently found that increasing the serotonergic tone with chronic administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) can reduce LID in 6-OHDA-lesioned rats, without affecting L-DOPA efficacy. To directly compare the effects of selective versus non-selective serotonin receptor activation, here we first tested different acute doses of the 5-HT1A/1B receptor agonist eltoprazine and 5-HTP on LID in order to identify doses of the individual compounds showing similar anti-dyskinetic efficacy in L-DOPA-primed dyskinetic rats. About 50% reduction of LID was observed with 0.1 mg/kg and 24 mg/kg of eltoprazine and 5-HTP, respectively; we then compared the effect of the two drugs, individually and in combination, on L-DOPA-induced stepping test in L-DOPA-naïve parkinsonian animals and LID over three weeks of L-DOPA treatment. Results showed that eltoprazine induced significant worsening of L-DOPA-mediated performance in the stepping test, while 5-HTP did not. Interestingly, combination of 5-HTP with eltoprazine prevented the reduction in the forelimb use induced by eltoprazine. Moreover, 5-HTP and eltoprazine given individually showed similar efficacy also upon chronic treatment, and had additive effect in dampening the appearance of LID when given in combination. Finally, chronic administration of eltoprazine and/or 5-HTP did not affect striatal serotonin innervation, compared to l-DOPA alone, as measured by serotonin transporter expression.

  15. Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

    Science.gov (United States)

    Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

    2015-07-01

    We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

  16. Comparison of Efficacy of Preventive and Therapeutic Vaccines Targeting the N Terminus of β-Amyloid in an Animal Model of Alzheimer's Disease.

    Science.gov (United States)

    Petrushina, Irina; Davtyan, Hayk; Hovakimyan, Armine; Davtyan, Arpine; Passos, Giselle F; Cribbs, David H; Ghochikyan, Anahit; Agadjanyan, Michael G

    2017-01-04

    Previously, we reported that Alzheimer's disease (AD) epitope vaccines (EVs) composed of N-terminal β-amyloid (Aβ42) B cell epitope fused with universal foreign T helper (Th) epitope(s) were immunogenic, potent, and safe in different amyloid precursor protein (APP) transgenic mice with early AD-like pathology. However, developing an effective therapeutic vaccine is much more challenging, especially when a self-antigen such as Aβ42 is a target. Here, we directly compare the efficacy of anti-Aβ42 antibodies in Tg2576 mice with low or high levels of AD-like pathology at the start of immunizations: 6-6.5 months for preventive vaccinations and 16-19 months for therapeutic vaccinations. EV in a preventive setting induced high levels of anti-Aβ antibodies, significantly reducing pathologic forms of Aβ in the brains of Tg2576 mice. When used therapeutically for immunesenescent Tg2576 mice, EV induced low levels of antibodies not sufficient for clearing of AD-like pathology. Separately, we demonstrated that EV was also not effective in 11-11.5-month-old Tg2576 mice with moderate AD-like pathology. However, we augmented the titers of anti-Aβ antibodies in transgenic (Tg) mice of the same age possessing the pre-existing memory Th cells and detected a significant decrease in diffuse and core plaques in cortical regions compared to control animals along with improved novel object recognition performance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  17. Monitoring the efficacy of steam and formaldehyde treatment of naturally Salmonella-infected layer houses

    DEFF Research Database (Denmark)

    Gradel, K.O.; Jørgensen, J.C.; Andersen, J.S.

    2004-01-01

    Aims: To monitor if a temperature-humidity-time treatment found to be effective in eliminating Salmonella in laboratory trials (Gradel et al. 2003) was efficient against Salmonella in naturally infected layer houses. Methods and Results: Six layer houses with natural Salmonella infections were...

  18. ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy.

    Science.gov (United States)

    Monga, Isha; Qureshi, Abid; Thakur, Nishant; Gupta, Amit Kumar; Kumar, Manoj

    2017-09-07

    Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb, (ii) ASPsiPred, and (iii) analysis tools like ASP-siOffTar ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully complementary mutant (Eff(mut)) and wild-type allele (Eff(wild)) with one mismatch by ASPsiPred(SVM) and ASPsiPred(matrix) , respectively. In ASPsiPred(SVM), 922 unique ASP-siRNAs with experimentally validated quantitative Eff(mut) were used. During 10-fold cross-validation (10nCV) employing various sequence features on the training/testing dataset (T737), the best predictive model achieved a maximum Pearson's correlation coefficient (PCC) of 0.71. Further, the accuracy of the classifier to predict Eff(mut) against novel genes was assessed by leave one target out cross-validation approach (LOTOCV). ASPsiPred(matrix) was constructed from rule-based studies describing the effect of single siRNA:mRNA mismatches on the efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first database, prediction algorithm, and off-target analysis tool that is expected to accelerate research in the field of RNAi

  19. Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA-hIL12 fusion protein against Mycobacterium tuberculosis in mice.

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    Full Text Available Tuberculosis (TB remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG, has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA and human interleukin 12 (hIL-12. Immune responses induced by the rMS in mice and protection against Mycobacterium tuberculosis (MTB were investigated. Administration of this novel rMS enhanced Th1-type cellular responses (IFN-γ and IL-2 in mice and reduced bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile, the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine also was significantly reduced. In conclusion, the rMS strain expressing the HBHA and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type response against TB, and the protective effect was equivalent to that of the conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load and alleviate histopathological damage in lungs of M. tuberculosis infected mice.

  20. Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2013-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (CTG group. On the contralateral side 10 teeth with gingival recession were treated with the same surgical procedures but in combination with platelet-rich plasma (CTGPRP group. We measured the keratinized tissue width. For statistical significance we used the Student's t-test. Results. The study reveled a statistical significance in reducing vertical deepress of recession by both used treatments. Root deepness in CTG and CTG-PRP group was 90% and 93.5%, respectively. With both surgical techniques we achieved larger zone of keratinized gingiva but with a wide zone of keratinized tissue in CTG - the PRP group. Conclusion. The concept regeneration technique with PRP and with the stimulating influence of platele activated growth factors results in the regeneration of deep periodontal tissue as an important prerequisite for the successful treatment of gingival recession.

  1. Therapeutic Efficacy of L-asparaginase in the Treatment of Refractory Midfacial Peripheral T-Cell Non-Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin's lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.

  2. Therapeutic efficacy of guided tissue regeneration and connective tissue autotransplants with periosteum in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2008-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practice as an ethiological factor of periodontal diseases, and symptoms of the disease have caused the development of various surgical procedures and techniques of the reconstruction of periodontal defects. The aim of this study was to verify efficacy of surgical procedures that include connective tissue autotransplants with periosteum and guided tissue regeneration for the treatment of gingival recession. Methods. The study included 20 teet with gingival recession, Müller class II and III. Ten teeth with gingival recession were treated with resorptive membrane and coronary guided surgical flap (GTR group. On the contralateral side 10 teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (TVT group. We measured the degree of epithelial attachment (DEA, width of subgingival curettage (WGC and vertical deepness of recession (VDR. For statistical significance we used Student's ttest. Results. The study revealed statistical significance in reducing VDR by both used treatments. Root deepness in GTR and TVT group was 63.5%, and 90%, respectively. With both surgical techniques we achieved coronary dislocation of the epithelial attachment, larger zone of gingival curettage, and better oral hygiene. Conclusion. Current surgical techniques are effective in the regeneration of deep periodontal spaces and the treatment of gingival recession. Significantly better results were achieved with the used coronary guided surgical flap than with guided tissue regeneration.

  3. Considerations for the sensible use of rodent models of inflammatory disease in predicting efficacy of new biological therapeutics in the clinic.

    Science.gov (United States)

    Arnett, Heather A; Viney, Joanne L

    2007-09-30

    Successful therapeutics for treating autoimmune and inflammatory diseases must be able to significantly dampen, and ideally reverse, the complex processes involved in the manifestation of inflammatory pathology in intact tissues and organs. Studies on human cells and tissues - both normal and diseased - are obviously critical for moving forward with a particular therapeutic strategy, but these types of studies are oftentimes limited in their complexity and usually fail to fully replicate the biology of the intact inflammatory environment and disease process. It is for this reason that development of a new drug generally relies on data generated from in vivo animal models that have been created to mimic aspects of the complex disease process in whole organs and whole animals. Although the intact animal model of disease provides the opportunity for key elements involved in inflammatory processes to be investigated in natural surroundings, the primary trigger for inflammatory activation in animal models is, by necessity, artificial and, of course, differs from the natural pathogenesis driving disease in humans. Despite the artificial way of inducing inflammatory responses, animal models of disease have proven invaluable for providing insight into the potential efficacy of new drugs, particularly when careful consideration has been given to ensure that the model system under study resembles the inflammatory pathway expected in human disease. The most common artificial approaches for stimulating inflammatory diseases in mice are quite varied, and range from overexpression or targeted deletion of genes in transgenic or knockout animals, immunization of animals with putative autoantigens, all the way to synthetic, chemical challenges. None of these artificial systems or triggers is wholly perfect at mimicking the complexity of human autoimmune and inflammatory diseases, but animal disease model data is an important, and very necessary, step in the path of drug development

  4. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis

  5. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles.

    Science.gov (United States)

    Naeem, Muhammad; Cao, Jiafu; Choi, Moonjeong; Kim, Woo Seong; Moon, Hyung Ryong; Lee, Bok Luel; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.

  6. Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye.

    Science.gov (United States)

    Choi, Won; Lee, Jee Bum; Cui, Lian; Li, Ying; Li, Zhengri; Choi, Ji Suk; Lee, Hyo Seok; Yoon, Kyung Chul

    2016-01-01

    Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (P plant extracts improved clinical signs, decreased inflammation, and ameliorated oxidative stress marker and ROS production on the ocular surface of the EDE model mice.

  7. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice.

    Science.gov (United States)

    Steinwede, Kathrin; Henken, Stefanie; Bohling, Jennifer; Maus, Regina; Ueberberg, Bianca; Brumshagen, Christina; Brincks, Erik L; Griffith, Thomas S; Welte, Tobias; Maus, Ulrich A

    2012-10-22

    Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae-induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail(-/-) mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.

  8. Efficacy of garlic (Allium sativum) extract applied as a therapeutic immersion treatment for Neobenedenia sp. management in aquaculture.

    Science.gov (United States)

    Militz, T A; Southgate, P C; Carton, A G; Hutson, K S

    2014-05-01

    Garlic, Allium sativum L., extract administered as a therapeutic bath was shown to have antiparasitic properties towards Neobenedenia sp. (MacCallum) (Platyhelminthes: Monogenea) infecting farmed barramundi, Lates calcarifer (Bloch). The effect of garlic extract (active component allicin) immersion on Neobenedenia sp. egg development, hatching success, oncomiracidia (larvae) longevity, infection success and juvenile Neobenedenia survival was examined and compared with freshwater and formalin immersion. Garlic extract was found to significantly impede hatching success (5% ± 5%) and oncomiracidia longevity (95% hatching success and mean oncomiracidia longevity of 37 ± 3 h. At much lower allicin concentrations (0.76 and 1.52 μL L(-1)), garlic extract also significantly reduced Neobenedenia infection success of L. calcarifer to 25% ± 4% and 11% ± 4%, respectively, compared with 55% ± 7% in the seawater control. Juvenile Neobenedenia attached to host fish proved to be highly resistant to allicin with 96% surviving 1-h immersion in 10 mL L(-1) (15.2 μL L(-1) allicin) of garlic extract. Allicin-containing garlic extracts show potential for development as a therapy to manage monogenean infections in intensive aquaculture with the greatest impact at the egg and larval stages. © 2013 John Wiley & Sons Ltd.

  9. Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point-of-care quantitative test with two established ELISA assays

    OpenAIRE

    Afonso, J.; S. Lopes; Gonçalves, R.; Caldeira, P; Lago, P; Tavares de Sousa, H; Ramos, J; Gonçalves, AR; Ministro, P; Rosa, I; Vieira, AI; Dias, CC; Magro, F

    2016-01-01

    BACKGROUND: Therapeutic drug monitoring is a powerful strategy known to improve the clinical outcomes and to optimise the healthcare resources in the treatment of autoimmune diseases. Currently, most of the methods commercially available for the quantification of infliximab (IFX) are ELISA-based, with a turnaround time of approximately 8 h, and delaying the target dosage adjustment to the following infusion. AIM: To validate the first point-of-care IFX quantification device available...

  10. Therapeutic efficacy of bevacizumab for age-related macular degeneration: what are the implications of CATT for routine management?

    Science.gov (United States)

    Ziemssen, Focke; Sobolewska, Bianka

    2011-11-01

    CATT (Comparison of Age-related macular degeneration [AMD] Treatment Trials) examined the efficacy of ranibizumab and bevacizumab for the treatment of neovascular AMD. This prospective, randomized, but unblinded trial revealed a significant improvement in vision with both treatments in terms of visual acuity; importantly, patients with juxtafoveal choroidal neovascularization (CNV) and retinal pigment epithelial detachments were not excluded from the study. Monthly treatment with the drugs resulted in similar increases in visual acuity, although angiograms indicated that ranibizumab was superior in terms of reducing retinal fluid and leakage. As the study also differentiated between a fixed regimen and an as-needed (pro re nata [PRN]) dosing regimen, a larger sample size and Bonferroni statistical correction were necessary. The equivalence of the PRN dosing of bevacizumab to the monthly treatment could not be confirmed. Almost all of the frequent deviations from the protocol (referring to retreatment criteria: 25.7-28.5%) resulted in under-treatment. Since this applied to both drugs equally, under-treatment alone could not explain the larger loss of visual acuity observed in the bevacizumab PRN arm. The PRN regimen was generally associated with a larger lesion size after 12 months compared with the fixed treatment regimens. The investigators accepted the drawbacks of an incomplete masking to allow co-payment by Medicare. As assessments of drug trials are often politically motivated, the higher demands of a non-inferiority trial compared with a superiority design must be emphasized. A comparison of the per-protocol and last-observation-carried-forward analysis has not yet been published; ongoing subgroup analysis might highlight the impact of different lesion characteristics. While CATT provided further evidence for the efficacy of bevacizumab treatment, differences in adverse events between the two treatments (e.g. a higher rate of serious adverse events with

  11. Assuring the Proper Analytical Performance of Measurement Procedures for Immunosuppressive Drug Concentrations in Clinical Practice: Recommendations of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Immunosuppressive Drug Scientific Committee.

    Science.gov (United States)

    Seger, Christoph; Shipkova, Maria; Christians, Uwe; Billaud, Elaine M; Wang, Ping; Holt, David W; Brunet, Mercè; Kunicki, Paweł K; Pawiński, Thomasz; Langman, Loralie J; Marquet, Pierre; Oellerich, Michael; Wieland, Eberhard; Wallemacq, Pierre

    2016-04-01

    Monitoring immunosuppressive drugs (ISDs) in blood or plasma is still a key therapeutic drug monitoring (TDM) application in clinical settings. Narrow target ranges and severe side effects at drug underexposure or overexposure make accurate and precise measurements a must. This overview prepared by the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology is intended to serve as a summary and guidance document describing the current state-of-the-art in the TDM of ISDs.

  12. Assessment of ivermectin therapeutic efficacy on third-stage larvae of Lagochilascaris minor in mice experimentally infected.

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    Barbosa, C A; Campos, D M; de Oliveira, J A

    1998-01-01

    In this study we evaluated the potential action of ivermectin on third-stage larvae, both at migratory and encysted phases, in mouse tissues after experimental infection with Lagochilascaris minor. Study groups I and II consisted of 120 mice that were orally administered 1,000 parasite eggs. In order to assess ivermectin action upon migratory larvae, group I (60 mice) was equally split in three subgroups, namely I-A, I-B, and I-C. On the 7th day after inoculation (DAI), each animal from the subgroup I-A was treated with 200 micrograms/Kg ivermectin while subgroup I-B was given 1,000 micrograms/Kg, both groups received a single subcutaneous dose. To assess the drug action on encysted larvae, group II was equally split in three subgroups, namely II-A, II-B, II-C. On the 45th DAI each animal was treated with ivermectin at 200 micrograms/Kg (subgroup II-A) and 1,000 micrograms/Kg (group II-B) with a single subcutaneous dose. Untreated animals of subgroups I-C and II-C were used as controls. On the 60th DAI all animals were submitted to larva search. At a dose of 1,000 micrograms/Kg the drug had 99.5% effectiveness on third-stage migratory larvae (subgroup I-B). Ivermectin efficacy was lower than 5% on third-stage encysted larvae for both doses as well as for migratory larvae treated with 200 micrograms/Kg.

  13. ASSESSMENT OF IVERMECTIN THERAPEUTIC EFFICACY ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN MICE EXPERIMENTALLY INFECTED

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    BARBOSA Carlos Augusto Lopes

    1998-01-01

    Full Text Available In this study we evaluated the potential action of ivermectin on third-stage larvae, both at migratory and encysted phases, in mouse tissues after experimental infection with Lagochilascaris minor. Study groups I and II consisted of 120 mice that were orally administered 1,000 parasite eggs. In order to assess ivermectin action upon migratory larvae, group I (60 mice was equally split in three subgroups, namely I-A, I-B, and I-C. On the 7th day after inoculation (DAI, each animal from the subgroup I-A was treated with 200 µg/Kg ivermectin while subgroup I-B was given 1,000 µg/Kg, both groups received a single subcutaneous dose. To assess the drug action on encysted larvae, group II was equally split in three subgroups, namely II-A, II-B, II-C. On the 45th DAI each animal was treated with ivermectin at 200 µg/Kg (subgroup II-A and 1,000 µg/Kg (group II-B with a single subcutaneous dose. Untreated animals of subgroups I-C and II-C were used as controls. On the 60th DAI all animals were submitted to larva search. At a dose of 1,000 µg/Kg the drug had 99.5% effectiveness on third-stage migratory larvae (subgroup I-B. Ivermectin efficacy was lower than 5% on third-stage encysted larvae for both doses as well as for migratory larvae treated with 200µg/Kg.

  14. Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

    Science.gov (United States)

    Zhu, Jing-jing; Zhang, Xin-xin; Miao, Yun-qiu; He, Shu-fang; Tian, Dan-mei; Yao, Xin-sheng; Tang, Jin-shan; Gan, Yong

    2017-01-01

    Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40–50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50 values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects. PMID:27917871

  15. The evolution of combined molecular targeted therapies to advance the therapeutic efficacy in melanoma: a highlight of vemurafenib and cobimetinib

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    Medina TM

    2016-06-01

    Full Text Available Theresa M Medina, Karl D Lewis Cutaneous Oncology Program, Division of Medical Oncology, School of Medicine, University of Colorado – Anschutz Medical Campus, Aurora, CO, USA Abstract: Metastatic melanoma is an aggressive, rapidly progressive disease which historically had very few effective treatment options. However, since 2011, the therapeutic landscape of melanoma has undergone a dramatic transformation with two distinct approaches and has catalyzed the successful advancement in the clinical field of immuno-oncology. In addition, the recognition of a key oncogenic driver mutation in melanoma, BRAF, stimulated the development of multiple potent kinase inhibitors which has also influenced the expansion and use of targeted agents in the practice of oncology. Vemurafenib, the initial BRAF inhibitor approved for the treatment of melanoma, was the first agent to demonstrate rapid clinical responses and significantly improved survival which was a clinical breakthrough in the treatment of melanoma. Although exciting and practice changing, the unparalleled responses with vemurafenib are usually not sustained. Further investigations delineated several mechanisms of acquired resistance which are most often mediated by the upregulation of the MAPK pathway. MEK inhibitors, another class of small-molecule inhibitors, were developed as an alternative agent to suppress the MAPK pathway downstream, independent from BRAF activation. Multiple studies have demonstrated the improvement in antitumor activity when MEK inhibitors are used in combination with BRAF inhibitors in the treatment of metastatic melanoma. This is a review of the investigations that led to the US Food and Drug Administration approval in 2015 of the combination of vemurafenib and cobimetinib, adding to the quickly growing armament for the treatment of advanced or metastatic melanoma with a BRAF V600 mutation. Keywords: melanoma, vemurafenib, cobimetinib

  16. Acanthamoeba polyphaga strain age and method of cyst production influence the observed efficacy of therapeutic agents and contact lens disinfectants.

    Science.gov (United States)

    Hughes, Reanne; Heaselgrave, Wayne; Kilvington, Simon

    2003-10-01

    The effects of age in culture and the type of medium used for induction of Acanthamoeba polyphaga (Ros) cysts on susceptibilities to polyhexamethylene biguanide (PHMB; 3 micro g/ml), chlorhexidine digluconate (30 micro g/ml), myristamidopropyl dimethylamine (20 micro g/ml), H(2)O(2) (3%), and two multipurpose contact lens solutions (MPS-1 and MPS-2, based on 1 micro g of PHMB per ml) were examined. Strain Ros-02 was cryopreserved on isolation in 1991, while strain Ros-91 had been in continuous axenic culture. Significant differences in susceptibilities to the disinfectants were found depending on the medium used for cyst preparation and the age of the test strain, with Ros-02 generally being more resistant. For example, the killing of Ros-91 cysts produced from an axenic culture of trophozoites in the presence of 50 mM MgCl(2) by MPS-2 was 4 logs, but the killing of Ros-02 by MPS-2 was only 2 logs (P < 0.05) and killing of both strains with cysts obtained from monoxenic cultures with Escherichia coli was only 1 log (P < 0.001). Assays repeated with different batches of the various cyst types gave consistent results. A batch of Ros-91 cysts stored at 4 degrees C and tested over an 8-week period with MPS-1 showed progressively increasing susceptibility to disinfection, although there was no loss of viability during storage (P < 0.01). These observations have important implications for the standardization and interpretation of Acanthamoeba disinfectant and therapeutic agent testing.

  17. Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases.

    Science.gov (United States)

    Cammarota, Giovanni; Pecere, Silvia; Ianiro, Gianluca; Masucci, Luca; Currò, Diego

    2016-01-01

    Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a 'virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT. © 2016 S. Karger AG, Basel.

  18. Assessment of the therapeutic efficacy and safety of natural orifice transluminal endoscopic surgery in patients with fulminant acute pancreatitis

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    ZHU Huiming

    2013-03-01

    Full Text Available ObjectiveTo evaluate the therapeutic effect of natural orifice transluminal endoscopic surgery (NOTES intervention in a cohort of patients treated for fulminant acute pancreatitis (FAP over a five-year period. MethodsBetween September 2007 and June 2012, 24 patients were treated with NOTES within 72 h of FAP onset and included 18 males and six females between the ages of 21-76 years old. The procedure was performed via the mouth to the stomach wall for penetration into the abdominal cavity and extraction of the inflammatory secretion followed by saline washes and lavage tube placement. Abdominal cavity lavage and peritoneal dialysis were carried out for one week. Outcome measures included abdominal pressure, bowel sounds, serum levels of inflammatory markers (tumor necrosis factor-alpha (TNFα, interleukin (IL-6, and IL-8, recovery time, and APACHE II score Data were analyzed using the Chi-squared test or F-test. ResultsIn 19 patients, the peritoneal effusion fluid volume removed during the NOTES procedure ranged from 200-2100 ml, and involved serous (n=7, blood (n=5, cellulose (n=5, and suppurative (n=2 fluids. In four patients, the lesser omental bursa effusion fluid volume ranged from 460-2500 ml, and involved serous (n=2 and blood (n=2 fluid. Abdominal pressure had decreased by day 2 after the NOTES procedure (8.60±2.65 vs. admission: 29.2±5.6 cm H2O. Intestinal peristalsis (admission: 1.68±1.02 times/minute was resolved by day 6 after the NOTES procedure (4.30±1.75 times/minute. Serum levels of TNFα, IL-6, and IL-8 were decreased significantly after the NOTES procedure (admission vs. day 6, all P<0.01. In addition, APACHE II score decreased after the NOTES procedure (admission: 12.76±6.68 vs. day 6: 6.46±1.84. The cure rate was 95.8%, and only one patient died (due to progressive multiple organ failure. The mean duration of hospital stay was 21.98±7.88 days. ConclusionNOTES intervention with extraction of the inflammatory

  19. Association of polymorphisms of cytosine arabinoside-metabolizing enzyme gene with therapeutic efficacy for acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    XU Pei-pei; WANG Xue-mei; XU Ke; Margaret Schultz; CHEN Bao-an; FENG Ji-feng; CHENG Lu; XIA Guo-hua; LI Yu-feng; QIAN Jun; DING Jia-hua; LU Zu-hong

    2012-01-01

    Background The cytosine arabinoside (Ara-C)-based chemotherapy is the major remedial measure for acute myeloid leukemia (AML).Deoxycytidine kinase (DCK) and cytidine deaminase (CDA) are the key enzymes in the metabolism ofAra-C.Many single nucleotide polymorphisms (SNPs) and haplotypes of DCK and CDA,which contribute to susceptibility to Ara-C,have been identified in Africans and Europeans.However,there has been no report about the relation among three SNPs in DCK (rs115543896,rs72552079,and rs111454937) and two SNPs in CDA (rs2072671 and rs60369023),and their clinical response to Ara-C for a Chinese population.In this study,we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML.Methods A total of 151 Chinese patients with AML were enrolled in our study.SNPs genotyping were performed using the MassARRAY system by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method.Results The results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count,and A allele frequency was significantly higher in the group ≤40 years,lower white blood ceil (WBC) count patients group and the group with platelet counts >60×109/L.Meanwhile,both DCKrs72552079 TC (OR=1.225,95% Cl=1.225-9.851,P=0.0192) and CDArs60369023 GA (OR=9.851,95% Cl=1.31-77.93,P=0.0263) significantly improved Ara-C-based chemotherapy response.While DCKrs11554389 AA (OR=0.147,95% Cl=0.027-0.801,P=0.0267) wasassociated with the decrease of Ara-C-based chemotherapy response.Conclusion It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients' therapy outcomes in a Chinese population.

  20. A comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator KR-22934 with the oxime K203 and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Pavlikova, Ruzena; Musilek, Kamil; Kuca, Kamil; Bajgar, Jiri; Jung, Young-Sik

    2011-03-01

    The potency of bispyridinium acetylcholinesterase reactivator KR-22934 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with the oxime K203 and commonly used oximes. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of KR-22934 was slightly higher than the reactivating efficacy of K203 and roughly corresponded to the reactivating efficacy of obidoxime and trimedoxime in blood and diaphragm. On the other hand, the oxime KR-22934 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied approximately corresponded to their reactivating efficacy. Based on the results, one can conclude that the oxime KR-22934 is not suitable for the replacement of commonly used oximes for the antidotal treatment of tabun poisoning in spite of its potency to reactivate tabun-inhibited acetylcholinesterase in the peripheral compartment (blood, diaphragm).

  1. A structured therapeutic education program for children and adolescents with type 1 diabetes: an analysis of the efficacy of the "Pediatric Education for Diabetes" project.

    Science.gov (United States)

    Mauri, Alessandra; Schmidt, Susanna; Sosero, Valentina; Sambataro, Maria; Nollino, Laura; Fabris, Francesco; Corò, Anna; Scantamburlo, Antonella; Cazziola-Merlotto, Michela; Ciani, Tania; Tessarin, Michele; Paccagnella, Agostino

    2017-02-07

    Therapeutic education for Type 1 Diabetes involves the process of transmitting knowledge and developing the skills and behavior required to treat the disease. guidelines agree on stressing the importance of therapeutic educational intervention in teaching self-management skills to children and adolescents with Type 1 Diabetes (T1D). This study presents the results of the "Pediatric Education for Type 1 Diabetes (T1D)" (PED) project, specifically designed for children and adolescents aged 6 to 16, and structured on guidelines indications, as part of a broader clinical-educational intervention for Type 1 diabetes. 24 patients with Type 1 diabetes (mean age: 12,13 y; SD = 1.48 y; range 9- 14) were studied in a 12-month PED structured project followed by a educational summer camp. All the activities were designed and organized by a multidisciplinary team (dietitian, pediatric diabetologist, nurse, psychologist and adult diabetologist). Glycated hemoglobin (HbA1C), knowledge about Type 1 Diabetes (T1D) (self-monitoring and nutrition), self- management (self-monitoring, nutrition and flexibility of medical treatment), and wellbeing were used as outcome measures. Data suggest that the PED had a positive impact on all the targeted levels indicated for recommended care. The results of this study seem to confirm the effectiveness in altering the three levels of "knowing", "know-how" and "wellbeing" required to optimize the quality of life of young patients with Type 1 diabetes. In addition, the proposed model, where a pediatric diabetologist always cooperates with an adult diabetologist, seems to be a permanent solution to the transitional gap widely discussed in the literature.

  2. Evaluation of therapeutic efficacy on combined use of clopidogrel and ozagrel sodium in the treatment of acute ischemic stroke

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    ZHAO Zhen

    2013-10-01

    Full Text Available Background Antiplatelet aggregation treatment has become a regular treatment of ischemic stroke. The affirmation of antiplatelet therapy is mainly derived from patients with clinical use, which can not provide the laboratory indexes for evaluation of a recognized accuracy. Studies have confirmed that the degree of platelet activation is associated with atherosclerosis and ischemic stroke, and recognized that both CD62p (α-platelet granule membrane glycoprotein and CD63 (lysosomal membrane glycoprotein were important indexes of platelet activation. This study aims to explore the differences of efficacy between combined use of clopidogrel and ozagrel sodium and monotherapy by aspirin in the treatment of acute ischemic stroke by investigating the expression of CD62p and CD63. Methods Flow cytometry was employed to detect CD62p and CD63 expression on circulating platelet in patients with ischemic stroke and normal control group. The positive rate of CD62p and CD63 was detected in patients with ischemic stroke who were treated with aspirin 0.15 g (single drug therapy and clopidogrel 75 mg + ozagrel sodium 80 mg (combination therapy before and after one and two weeks' treatment. National Institute of Health Stroke Scale (NIHSS scores were measured in patients with ischemic stroke at the same time in three periods respectively to evaluate the improvement of neural function. Results Platelet CD62p and CD63 positive expression rate in ischemic stroke group were higher than normal control group before treatment (P = 0.001, 0.032. CD62p and CD63 positive expression rate and NIHSS score were measured at different times, and the differences were statistically significant (F = 56.693, P = 0.000; F = 21.544, P = 0.000; F = 216.271, P = 0.000, respectively. Compared with before treatment, CD62p and CD63 positive expression rate and NIHSS score decreased significantly after treatment (P = 0.000, for all, but the differences between aspirin group and combination

  3. Evaluation of the Efficacy of Sex Pheromones and Food Attractants Used to Monitor and Control Synanthedon Myopaeformis (Lepidoptera: Sesiidae

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    František Kocourek

    2016-01-01

    Full Text Available Synanthedon myopaeformis (Borkhausen, 1789 (Lepidoptera: Sesiidae is a prominent pest of commercial apple orchards in Europe. the sex pheromones of S. myopaeformis and food attractants based on apple juice, beer and red wine were evaluated as tools for monitoring and control the populations of S. myopaeformis in apple orchards in the Czech Republic. For monitoring S. myopaeformis flight activity, trap designs were also evaluated, and the results indicated that wing traps were more suitable than delta traps because of their high efficacy even at low population densities of S. myopaeformis. The flight activity patterns of S. myopaeformis showed high intrapopulation variability and variability between years. The use of pheromones as a mating disruption technique led to a decrease of tree injury in comparison to untreated controls during the three years of the experiment. The reduction of the number of S. myopaeformis larvae per tree on a 14-ha plot treated subjected to the mating disruption technique reached 56 % in the third year of the experiment. In the three-year experiment using food attractants for the mass trapping of S. myopaeformis, catches of S. myopaeformis in traps using a combination of beer and apple juice (50:50 at a density of 4 traps/ha on a 4-ha plot increased more than 4-fold.

  4. Therapeutic efficacy of milbemycin oxime/praziquantel oral formulation (Milbemax® against Thelazia callipaeda in naturally infested dogs and cats

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    Motta Bruna

    2012-05-01

    Full Text Available Abstract Background Over the last few decades, canine and feline thelaziosis caused by Thelazia callipaeda eye worms has gained the attention of the veterinary community due to the spread of this ocular infestation in geographical areas previously regarded as non endemic. The therapeutic efficacy of milbemycin oxime/praziquantel tablets (Milbemax® against T. callipaeda was tested in naturally infested dogs and cats. Methods From January 2009 to July 2011 a placebo controlled and randomized field study was conducted in T. callipaeda endemic areas of Switzerland (CH and Italy (ITA involving client-owned animals. Dogs (n = 56 and cats (n = 31 were physically examined at enrolment Day 0 (D0 and twice afterwards (D7 and D14. Infested animals were orally treated with Milbemax® or with placebo tablets on D0 and, if an animal was found still infested with T. callipaeda, also on D7. On D14 nematodes were flushed from the conjunctiva, identified and counted. Results Out of 56 dogs, 43 were included in the statistical analysis, whereas 13 were excluded because the products under investigation were not administered with food, as required by the label. On D7 and D14, 72.7% and 90.9% of treated dogs were eye worm free, whereas in the placebo group 95.2% and 76.2% still harbored nematodes, resulting in a mean percentage worm count reduction for the Milbemax® group of 86.1% and 96.8%, respectively. Both results were significantly higher (p = 0.0001 than the placebo group. Out of the 31 cats included in the study at D7 and D14, 53.3% and 73.3% treated with Milbemax® were free of T. callipaeda, while 81.3% and 73.3 in the placebo group were still harbouring eye worms, resulting in a mean percentage worm count reduction for the treated group of 62.2% and 80.0%, respectively. Both results were significantly higher (p = 0.0106 and p = 0.0043 than the placebo group. Conclusions The commercial formulation of milbemycin oxime at the minimal dose

  5. Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells

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    Chatterjee S

    2015-08-01

    Full Text Available Sushmita Chatterjee, Nirmal Thaker, Abhijit DeMolecular Functional Imaging Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, IndiaAbstract: Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5 protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated 131I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy Cobalt60 radiation shows significant radiosensitization effect (P=0.0002. In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019 by 50 µ Ci 131I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS

  6. Comparison of the therapeutic efficacy of double-modality therapy, phonophoresis and cryotherapy in the management of musculoskeletal injuries in adult Nigerian subjects.

    Science.gov (United States)

    Onuwe, H A; Amadi, K; Odeh, S O

    2013-12-20

    This study was designed to compare the efficacy of double-modality therapy, phonophoresis and cryotherapy in the management of pain among subjects who suffered from musculoskeletal injuries (MSIs).Sixty (60) subjects were assigned randomly to one of three groups: DMT group (n=20) received cryotherapy and 15% methyl salicylate phonophoresis, PHONO group (n=20) received 15% methyl salicylate phonophoresis and CRYO group (n=20) received cryotherapy and "sham‟ phonophoresis. Ultrasound at an intensity of 1.5 W/cm² and frequency of 1MHz was used to apply methyl salicylate while intermittent cryotherapy was the mode of application. Subjects‟ pre- and post-treatment pain perception scores (PPS) using visual analogue scale (VAS) were assessed and the sessions of treatment in all groups were recorded. Treatment was administered on alternate days and discharges were made in all groups when subjects were pain free. A total of 275 treatment sessions was recorded - 72 (26.2%) in DMT, 105 (38.2%) in PHONO and 98 (35.6%) in CRYO group respectively which indicated no significant difference (P>0.05). Nineteen (19), thirteen (13) and twelve (12) subjects were pain free in DMT, CRYO or PHONO groups respectively after 1 to 5 treatments. The difference in the severity of pain was significant (Pcryotherapy were equally effective. The study has demonstrated therapeutic efficacy of DMT, but it was not superior to the single treatment protocol of phonophoresis or cryotherapy. However, it might take fewer sessions in the DMT group to treat and make more than 90% of the subjects pain free and fit to return to active performance.

  7. The Jak2 Inhibitor, G6, Alleviates Jak2-V617F–Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow

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    Annet Kirabo

    2011-11-01

    Full Text Available We recently developed a Janus kinase 2 (Jak2 small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F– mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F–mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F–mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6. In the liver, G6 eliminated Jak2-V617F–driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the spleno-megaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho–signal transducer and activator of transcription 5 (STAT5. It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67% on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F–mediated myeloproliferative neoplasia.

  8. Reliability and validation of the joint dysfunction index as a new assessment instrument for therapeutic efficacy for Kashin-Beck disease.

    Science.gov (United States)

    Yu, Fang-Fang; Xia, Chuan-Tao; Fang, Hua; Wang, Di-Miao; Guo, Xiong

    2016-11-01

    The objective of this study was to evaluate the reliability and validity of the joint dysfunction index (JDI) for assessment of therapeutic efficacy for Kashin-Beck disease (KBD). In an initial survey, completed questionnaires were obtained from 276 of 281 patients (98.2 %). A follow-up survey was completed with 64 KBD patients among 276 cases. A third survey selected 60 KBD patients who underwent intra-articular injection of sodium hyaluronate in the knees ascertained from the findings of the second questionnaire. Reliability was assessed using test-retest, "split-half" reliability and Cronbach's alpha coefficient. Factor analysis and item-to-domain correlation were used to analyze validity. The coefficient of variation (CV) was used to measure the sensitivity of scale. Feasibility assessment included consideration of completion time, rate of recovery, and time of completion. Reliability analysis comprised a test-retest correlation coefficient of 0.404-0.546 and a kappa test of 0.404-0.546. Internal consistency analysis comprised a Cronbach alpha coefficient of 0.689 and a split-half coefficient of 0.677. Principal component factor analysis for validity testing extracted a common factor with a cumulative variance contribution of 45.44 %. The JDI score from 276 KBD cases revealed no significant difference associated with age, gender, education, or the body mass index. Sensitivity analysis showed that there was no significant difference between pre-treatment and post-treatment values, with a CV of 96.55-172.06 %. In conclusion, the JDI can be used to evaluate the efficacy of agents used to treat KBD.

  9. In vitro and in vivo therapeutic efficacy of CXCR4 antagonist BKT140 against human non-small cell lung cancer.

    Science.gov (United States)

    Fahham, Duha; Weiss, Ido D; Abraham, Michal; Beider, Katia; Hanna, Wald; Shlomai, Zippora; Eizenberg, Orly; Zamir, Gideon; Izhar, Uzi; Shapira, Oz M; Peled, Amnon; Wald, Ori

    2012-11-01

    CXCR4/CXCL12 interactions promote non-small cell lung cancer (NSCLC) growth and dissemination. Furthermore, this axis might promote NSCLC resistance to chemotherapy and/or radiotherapy. Therefore, the CXCR4/CXCL12 axis constitutes an attractive therapeutic target for the treatment of NSCLC. We aimed to characterize the therapeutic efficacy of the novel CXCR4 antagonist BKT140 against human NSCLC. We determined the CXCR4 expression in 5 NSCLC cell lines (H358, A549, H460, H1299, and L4). We then tested the colony-forming capacity and proliferation of these cells in the presence of CXCL12 and BKT140. Next, we measured the in vivo growth of A549 and H460 xenografts with or without BKT140 treatment. Finally, we examined, in vitro, the potential antiproliferative effect of BKT140 combined with cisplatin or paclitaxel and after irradiation of NSCLC cells. All tested cell lines expressed CXCR4 and showed increased colony formation in response to CXCL12 stimulation. BKT140 reduced the colony-forming capacity of NSCLC cells. Proliferation assays demonstrated both cytotoxic and cytostatic properties for this peptide. H460 cells were the most sensitive to BKT140 and A549 cells the least. Subcutaneous administration of BKT140 significantly delayed the development of H460 xenografts and showed a similar trend for A549 xenografts. Finally, the antiproliferative effects of BKT140 appears to be additive to those of chemotherapeutic drugs and radiotherapy. Targeting the CXCL12/CXCR4 axis with BKT140 attenuated NSCLC cells tumor growth and augmented the effects of chemotherapy and radiotherapy. Future research will benefit from delineating the downstream mechanism of BKT140 action and defining BKT140 susceptibility markers. Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.

  10. Enhanced therapeutic efficacy and amelioration of cisplatin-induced nephrotoxicity by quercetin in 1,2-dimethyl hydrazine-induced colon cancer in rats.

    Science.gov (United States)

    Li, Qing-Chun; Liang, Yun; Hu, Guang-Rui; Tian, Yuan

    2016-01-01

    The aim of quercetin treatment in combination of cisplatin (CP)-induced nephrotoxicity as well on 1,2-dimethyl hydrazine (DMH)-induced colon cancer. In this study, animals are exposed to DMH hydrochloride to induce colon cancer. In these groups, nephrotoxicity was assessed with the help of blood urea nitrogen, urea, and creatinine. The antitumor activity of quercetin and CP assessed with the help of number of aberrant crypts and foci formation. Tumor size in different treatment group determined with the help of vernier caliper. CP is one of the most widely used antineoplastic drugs against colon cancer, but it has a major dose-limiting drawbacks of causing nephrotoxicity. Therefore, there is a need for a novel therapeutic regimen which will reduce the nephrotoxicity and enhance the anticancer activity of CP. The protective effect of quercetin on CP-induced nephrotoxicity is well-known. Moreover, quercetin is proven to have antitumor activity in colon cancer. Keeping all the facts in view, this study was conceived to evaluate the role of quercetin on therapeutic efficacy and nephrotoxicity of CP in DMH-induced colon cancer in male Sprague-Dawley rats. Treatment of quercetin with CP (7.5 mg/kg) prevents the CP-induced nephrotoxicity along with enhance the anticancer activity confirmed by the reduction of aberrant crypt foci number. Treatment of CP and quercetin alone leads to significant increase in the anticancer activity as compared to control colon tumor rats. In DMH-induced colon cancer model, combination of quercetin and CP ameliorates CP-induced nephrotoxicity as well as enhanced antitumor activity.

  11. Neither in vivo MRI nor behavioural assessment indicate therapeutic efficacy for a novel 5HT1A agonist in rat models of ischaemic stroke

    Directory of Open Access Journals (Sweden)

    Modo Michel M

    2009-07-01

    Full Text Available Abstract Background 5HT1A agonists have previously been shown to promote recovery in animal models of stroke using ex vivo outcome measures which have raised the hopes for a potential clinical implementation. The purpose of this study was to evaluate the potential neuroprotective properties of a novel 5HT1A agonist DU123015 in 2 different models of transient focal ischaemic stroke of varying severities using both in vivo neuroimaging and behavioural techniques as primary outcome measures. For these studies, the NMDA receptor antagonist MK-801 was also utilized as a positive control to further assess the effectiveness of the stroke models and techniques used. Results In contrast to MK-801, no significant therapeutic effect of DU123015 on lesion volume in either the distal MCAo or intraluminal thread model of stroke was found. MK-801 significantly reduced lesion volume in both models; the mild distal MCAo condition (60 min ischaemia and the intraluminal thread model, although it had no significant impact upon the lesion size in the severe distal MCAo condition (120 min ischaemia. These therapeutic effects on lesion size were mirrored on a behavioural test for sensory neglect and neurological deficit score in the intraluminal thread model. Conclusion This study highlights the need for a thorough experimental design to test novel neuroprotective compounds in experimental stroke investigations incorporating: a positive reference compound, different models of focal ischaemia, varying the duration of ischaemia, and objective in vivo assessments within a single study. This procedure will help us to minimise the translation of less efficacious compounds.

  12. Efficacy of StaMPS technique for monitoring surface deformation in L'Aquila, Italy

    Science.gov (United States)

    Tiwari, A.; Dwivedi, R.; Narayan, A. B.; Dikshit, O.; Singh, A. K.

    2014-11-01

    This research work investigates the efficacy of the Stanford Method for Persistent Scatterer Interferometry (StaMPS) in measuring the surface deformation over the L'Aquila region, Italy just before an event of earthquake of magnitude Mw 6.3 by using seven descending Envisat C-Band ASAR images. The results show that the StaMPS technique successfully extracted sufficient number of Persistent Scatterers (PS) to derive a one dimensional (1D) time series displacement map which shows the deformation rates up to 59 mm/year in the satellite Line of Sight (LOS) direction and 50.8 mm/year in the direction opposite to the satellite LOS. Further, several deformation gradients are also observed from this map which indicate the occurrence of multiple crustal movement mechanism. Another dataset of 14 ASAR images is processed covering a time period before and after the earthquake in the study area to validate the results obtained by the previous dataset. We observed that the generated displacement map follows the deformation characteristics of the earlier displacement map in terms of magnitude and surface movement. We conclude that the generated displacement maps validate the presence of a normal fault mechanism with a tectonic process stretching in a NW-SE direction as predicted by earlier research studies.

  13. Efficacy and cost analysis of transrectal ultrasound-guided prostate biopsy under monitored anesthesia

    Institute of Scientific and Technical Information of China (English)

    Sung Gu Kang; Bum Sik Tae; Sam Hong Mine; Young Hwu Ko; Seok Ho Kang; Jeong Gu Lee; Je Jong Kim; Jun Cheon

    2011-01-01

    @@ Sedation may result in reduction in pain during transrectal ultrasound(TRUS)-guided prostate biopsies.We aimed to evaluate the efficacy and safety of a combination of propofol and remifentanil infusion during TRUS-guided prostate biopsy and the related increases in health care costs.From January to September 2010,100 men undergoing a transrectal prostate biopsy were randomized into two groups.In Group 1,[50]patients received a combined infusion of propofol and remifentanil; in Group 2,[50]patients received lidocaine jelly.After TRUS-guided biopsies were performed,pain and patient satisfaction were evaluated by a 10-point visual analog scale (VAS),and a cost-related patient satisfaction questionnaire was completed by all patients.Patients were also asked whether they would be willing to undergo repeat biopsy by the same method.Patients in Group 1 showed a significantly lower VAS score than those in Group 2 (mean VAS score: 0.9士1.1 versus 6.312.5; P<0.001).In addition,the patient satisfaction scale was significantly higher in Group 1(P=0.002).Although the overall cost was significantly higher in Group 1(P=0.006),patient satisfaction scales considering cost were also higher in this group (P=0.009).A combination of propofol and remifentanil is a safe and effective way to decrease patient pain and increase patient satisfaction during TRUS-guided prostate biopsy.Although the costs were higher in the group that received sedation,as expected,the patients exhibited heightened satisfaction and willingness to repeat biopsies by the same method.

  14. How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders.

    Science.gov (United States)

    Vandervert, Larry

    2015-01-01

    Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein's cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue that: (1) The foundational basis of the central executive begins in infancy as attentional control during the establishment of working memory, (2) In accordance with Akshoomoff, Courchesne and Townsend's and Leggio and Molinari's cerebellar sequence detection and prediction models, the rigors of volitional control demands of music training can enhance voluntary manipulation of information in thought and movement, (3) The music training-enhanced blending of cerebellar internal models in working memory as can be experienced as intuition in scientific discovery (as Einstein often indicated) or, equally, as moments of therapeutic advancement toward goals in the development of voluntary control in neurological disorders, and (4) The blending of internal models as in (3) thus provides a mechanism by which music training enhances central executive processes in working memory that can lead to scientific discovery and improved therapeutic outcomes in neurological disorders. Within the framework of Leggio and Molinari's cerebellar sequence detection model, it is determined that intuitive steps forward that occur in both scientific discovery and during therapy in those with neurological disorders operate according to the same mechanism of adaptive error-driven blending of cerebellar internal models. It is concluded that the entire framework of the central executive structure of working memory is a product of the cerebrocerebellar system which can, through the learning of internal models

  15. Practice and Result Analysis of Therapeutic Drug Monitoring%治疗药物监测实践及结果分析

    Institute of Scientific and Technical Information of China (English)

    林宇涵; 许双临; 陈子春

    2012-01-01

      目的分析治疗药物监测结果,评价其临床效果和意义.方法采用 HPLC 法测定5种药物的血药浓度,对监测结果进行分析、统计.结果治疗药物监测结果在有效治疗窗内的仅占56.7%.监测值在低、中、高血药浓度范围内出现临床症状、症状控制、中毒症状的比例分别为90.5%、94.1%、100%.结论治疗药物监测对临床个体化给药具有重要意义.%  Objective To analyze and evaluate the results of therapeutic drug nonitoring (TDM) data. Methods The blood concentrations of 5 drugs were measured by HPLC, analysis and statistics of TDM data were carried out. Results Among all the TDM concentration, only 56.7% was within the therapeutic window. The monitoring value at low, medium and high blood drug level respectively within the scope of clinical symptoms appear, symptom under control, toxic symptom ratio was 90.5%, 94.1% and 100%. Conclusion Therapeutic drug monitoring is significant for individual administration in clinical.

  16. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  17. Therapeutic Efficacy and Safety of Percutaneous Ethanol Injection with or without Combined Radiofrequency Ablation for Hepatocellular Carcinomas in High Risk Locations

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Dong Ik; Lee, Min Woo; Rhim, Hyunchul; Choi, Dongil; Kim, Young-sun; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)

    2013-07-01

    To evaluate the therapeutic efficacy and safety of percutaneous ethanol injection (PEI) alone and combined with radiofrequency ablation (RFA) for hepatocellular carcinomas (HCCs) in high risk locations. We performed PEI for HCCs in RFA-high risk locations, either alone or in combination with RFA. There were 20 HCCs (1.7 ± 0.9 cm) in 20 patients (PEI group: n = 12; PEI + RFA group: n = 8). We evaluated technical success, local tumor progression and complications in both groups. Technical success was achieved in all HCCs in both groups. During follow-up, local tumor progression was found in 41.7% (5/12) in the PEI group, whereas 12.5% (1/8) for the PEI + RFA group (p = 0.32). Bile duct dilatation was the most common complication, especially when the tumors were in periportal locations; 55% (5/9) in the PEI group and 50% (2/4) in the PEI + RFA group (p = 1.00). One patient in the PEI group developed severe biliary stricture and upstream dilatation that resulted in atrophy of the left hepatic lobe. One patient treated with PEI + RFA developed cholangitis and an abscess. Combined PEI and RFA treatment has a tendency to be more effective than PEI alone for managing HCCs in high risk locations, although the difference is not statistically significant. Even though PEI is generally accepted as a safe procedure, it may cause major biliary complications for managing HCCs adjacent to the portal vein.

  18. Antibacterial activity and therapeutic efficacy of Fl-PRPRPL-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection

    Directory of Open Access Journals (Sweden)

    Thangamani S

    2015-10-01

    Full Text Available Shankar Thangamani,1 Manish Nepal,2 Jean Chmielewski,2 Mohamed N Seleem11Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA; 2Department of Chemistry, Purdue University, West Lafayette, IN, USAAbstract: The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-PRPRPL-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-PRPRPL-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively. Fl-PRPRPL-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-PRPRPL-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-PRPRPL-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and interleukin-1 beta (IL-1β in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-PRPRPL-5 in the treatment of staphylococcal skin infections.Keywords: antimicrobial peptides, Staphylococcus aureus, biofilms, anti-inflammatory, skin infection

  19. Antibacterial activity and therapeutic efficacy of Fl-P(R)P(R)P(L)-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection.

    Science.gov (United States)

    Thangamani, Shankar; Nepal, Manish; Chmielewski, Jean; Seleem, Mohamed N

    2015-01-01

    The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-P(R)P(R)P(L)-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-P(R)P(R)P(L)-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-P(R)P(R)P(L)-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-P(R)P(R)P(L)-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-P(R)P(R)P(L)-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-P(R)P(R)P(L)-5 in the treatment of staphylococcal skin infections.

  20. Antibacterial activity and therapeutic efficacy of Fl-PRPRPL-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection

    Science.gov (United States)

    Thangamani, Shankar; Nepal, Manish; Chmielewski, Jean; Seleem, Mohamed N

    2015-01-01

    The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-PRPRPL-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-PRPRPL-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-PRPRPL-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-PRPRPL-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-PRPRPL-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-PRPRPL-5 in the treatment of staphylococcal skin infections. PMID:26543355

  1. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy.

    Science.gov (United States)

    Watanabe, Satoru; Chan, Kitti Wing-Ki; Dow, Geoffrey; Ooi, Eng Eong; Low, Jenny G; Vasudevan, Subhash G

    2016-03-01

    Although the antiviral drug celgosivir, an α-glucosidase I inhibitor, is highly protective when given twice daily to AG129 mice infected with dengue virus, a similar regimen of twice daily dosing did not significantly reduce serum viral loads in patients in a recent clinical trial. This failure presumably might reflect the initiation of treatment when patients were already viremic. To better mimic the clinical setting, we used viruses isolated from patients to develop new mouse models of DENV1 and DENV2 infection and employed the models to test the twice daily treatment, begun either on the day of infection or on the third day post-infection, when the mice had peak of viremia. We found that, although the treatment started on day 0 was effective on viral load reduction, it provided no benefit when begun on day 3, indicating that in vivo antiviral efficacy becomes less prominent once viremia reaches the peak level. To determine if the therapeutic regimen in humans could be improved, we tested regimen of four-times daily treatment and found that the treatment significantly reduced viremia, suggesting that a similar regimen may be effective in a human clinical trial. A new clinical trial to investigate an altered dosing regimen has been approved (NCT02569827).

  2. The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

    Directory of Open Access Journals (Sweden)

    Robert A. Mitchell

    2016-01-01

    Full Text Available Background. Infliximab (IFX therapeutic drug monitoring (TDM allows for objective decision making in patients with inflammatory bowel disease (IBD and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67% and 2 (83% had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P=0.098. Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

  3. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays

    Directory of Open Access Journals (Sweden)

    Rezende VM

    2013-08-01

    Full Text Available Vinicius Marcondes Rezende,1 Ariane Rivellis,1 Mafalda Megumi Yoshinaga Novaes,1 Dalton de Alencar Fisher Chamone,2 Israel Bendit1,21Laboratory of Tumor Biology, 2Department of Hematology, School of Medicine, University of São Paulo, São Paulo, BrazilBackground: Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring.Methods: A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The method was validated according to the requirements of the US Food and Drug Administration and Brazilian National Health Surveillance Agency within the range of 0.500–10.0 µg/mL with a limit of detection of 0.155 µg/mL. Stability data for the analyte are also presented.Conclusion: Given that the validated method has proved to be linear, accurate, precise, and robust, it is suitable for pharmacokinetic assays, such as bioavailability and bioequivalence, and is being successfully applied in routine therapeutic drug monitoring in the hospital service.Keywords: imatinib, high-performance liquid chromatography-mass spectrometry, therapeutic

  4. Limited sampling strategies for therapeutic drug monitoring of amikacin and kanamycin in patients with multidrug-resistant tuberculosis

    NARCIS (Netherlands)

    Dijkstra, J.A.; van Altena, R.; Akkerman, O. W.; de Lange, W. C. M.; Proost, J. H.; van der Werf, T. S.; Kosterink, J. G. W.; Alffenaar, J. W. C.

    2015-01-01

    Amikacin and kanamycin are considered important and effective drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). Unfortunately, the incidence of toxicity is high and is related to elevated drug exposure. In order to achieve a balance between efficacy and toxicity, a population phar

  5. Prescription Opioid Usage and Abuse Relationships: An Evaluation of State Prescription Drug Monitoring Program Efficacy

    Directory of Open Access Journals (Sweden)

    Richard M. Reisman

    2009-01-01

    Full Text Available Context: The dramatic rise in the use of prescription opioids to treat non-cancer pain has been paralleled by increasing prescription opioid abuse. However, detailed analyses of these trends and programs to address them are lacking.Objective: To study the association between state shipments of prescription opioids for medical use and prescription opioid abuse admissions and to assess the effects of state prescription drug monitoring programs (PDMPs on prescription opioid abuse admissions.Design and Setting: A retrospective ecological cohort study comparing state prescription opioid shipments (source: Automation of Reports and Consolidated Orders Systems database and inpatient admissions for prescription opioid abuse (source: Treatment Episode Data Set in 14 states with PDMPs (intervention group and 36 states without PDMPs (control group for the period 1997–2003.Results: From 1997 to 2003, oxycodone, morphine, and hydrocodone shipments increased by 479%, 100%, and 148% respectively. Increasing prescription oxycodone shipments were significantly associated with increasing prescription opioid admission rates (p 0.001. PDMP states had significantly lower oxycodone shipments than the control group. PDMP states had less increase in prescription opioid admissions per year (p = 0.063. A patient admitted to an inpatient drug abuse rehabilitation program in a PDMP state was less likely to be admitted for prescription opioid drug abuse (Odds ratio = 0.775, 95% Confidence Interval 0.764–0.785.Conclusions: PDMPs appear to decrease the quantity of oxycodone shipments and the prescription opioid admission rate for states with these programs. Overall, opioid shipments rose significantly in PDMP states during the study period indicating a negligible “chilling effect” on physician prescribing.

  6. Monitoring in vitro efficacy of Holarrhena antidysenterica against multidrug resistant enteropathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Shakti Rath

    2014-02-01

    Full Text Available Objective: To assess antibacterial activities of leaf and bark extracts of Holarrhena antidysenterica (H. antidysenterica, used by an Indian aborigine for ailments of human gastrointestinal tract, against eight extended spectrum β-lactamase producing multidrug resistant enteropathogens. Methods: Antibacterial activities of eight solvent-extracts of the plant were monitored by the agar-well diffusion method on lawns of all bacteria. Further, minimum inhibitory concentrations and minimum bactericidal concentrations of the best three solvent extracts were determined by the micro-broth dilution method. Preliminary phytochemical analysis of the active leaf and bark extracts were carried out. Results: It was found that Enterobacter aerogenes was resistant to 14 of 16 antibiotics, likewise, Escherichia coli to 13, Klebsiella sp. to 14, Salmonella paratyphi to 7, Salmonella typhi to 15, Shigella dysenteriae and Shigella sonnei to 14, Vibrio cholerae to 4 of 16 antibiotics. It was found that plant-extracts with petroleum ether and n-hexane had the least antibacterial activity. Extracts of leaves with chloroform, methanol, and water registered moderate antibacterial activity, whereas bark-extracts with ethyl acetate, acetone, and ethanol had a comparatively higher antibacterial activity on all these strains. Maximum sizes of zone of inhibition due to leaf extracts with ethyl acetate, acetone, and ethanol, and on the other hand, bark extracts with ethyl acetate, acetone and methanol were recorded against these bacteria; minimum inhibitory concentration and minimum bactericidal concentration values of specifically these extracts were determined. Phytochemical analysis of the methanolic bark extract of H. antidysenterica confirmed the presence of alkaloids, terpenoids, reducing sugars, tannins, and flavonoids. Conclusions: Data analysis revealed that leaves and bark of H. antidysenterica could serve as complementary/supplementary drugs along with suitable

  7. Application of a wrist dosimeter prototype for radiation monitoring ({sup 153}Sm) during a therapeutic procedure simulation

    Energy Technology Data Exchange (ETDEWEB)

    Cecatti, S G P [Fundacentro, Ministerio do Trabalho e Emprego, Rua Capote Valente, 710, 05409-002, Sao Paulo (Brazil); Guimaraes, M I C C [Centro de Medicina Nuclear, Universidade de Sao Paulo, Travessa da Rua Dr. Ovidio Pires de Campos s/n, 05403-010, Sao Paulo (Brazil); Caldas, L V E [Instituto de Pesquisas Energeticas e Nucleares, IPEN-Comissao Nacional de Energia Nuclear, Avenida Professor Lineu Prestes, 2242, 05508-000, Sao Paulo (Brazil)], E-mail: scecatti@fundacentro.gov.br, E-mail: ines@hcnet.usp.br, E-mail: lcaldas@ipen.br

    2009-12-01

    Gamma and beta radiation emitting radiopharmaceuticals are handled in nuclear medicine services, and in many cases there is only individual monitoring of gamma radiation. In this paper, the results obtained using a wrist dosimeter prototype (CaSO{sub 4}:Dy+Teflon pellets) show that the doses for workers occupationally exposed to beta radiation from {sup 153}Sm are not negligible. It is important that this dose is evaluated, and it has to be taken into consideration in the individual monitoring system.

  8. Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience

    Science.gov (United States)

    Hirano, Ryuichi; Sakamoto, Yuichi; Kitazawa, Junichi; Yamamoto, Shoji; Tachibana, Naoki

    2016-01-01

    Background Vancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Materials and methods The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated. Results Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate. Conclusion Our ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections. PMID:27789965

  9. Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring.

    Science.gov (United States)

    Shibata, Mai; Hashi, Sachiyo; Nakanishi, Haruka; Masuda, Satohiro; Katsura, Toshiya; Yano, Ikuko

    2012-12-01

    The purpose of this study was to develop an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics for routine therapeutic monitoring. The antiepileptics used in the analyses were carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam, clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide. After protein precipitation of 50 μL plasma with methanol, the supernatant was diluted with water or was evaporated to dryness and reconstituted with mobile phase in the case of benzodiazepines. Separation was achieved on an Acquity UPLC BEH C₁₈ column with a gradient mobile phase of 10 mm ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.4 mL/min. An Acquity TQD instrument in multiple reaction monitoring mode with ion mode switching was used for detection. All antiepileptics were detected and quantified within 10 min, with no endogenous interference. All the calibration curves showed good linearity in the therapeutic range (r²  < 0.99). The precision and accuracy values for intra- and inter-assays were within ±15% except for phenobarbital and tiagabine. A good correlation was observed between the concentration of clinical samples measured by the new method described here and the conventional methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than those detected by the immunoassays, which might be caused by the cross-reaction of antibodies with their metabolites. In conclusion, we developed a simple and selective UPLC-MS/MS method suitable for routine therapeutic monitoring of antiepileptics.

  10. A comparison of the reactivating and therapeutic efficacy of two newly developed oximes (k727 and k733) with oxime k203 and trimedoxime in tabun-poisoned rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Sepsova, Vendula; Tumova, Martina; Horova, Anna; Musilek, Kamil

    2015-04-01

    The reactivating and therapeutic efficacy of three original bispyridinium oximes (K727, K733 and K203) and one currently available oxime (trimedoxime) was evaluated in tabun-poisoned rats and mice. The oxime-induced reactivation of tabun-inhibited acetylcholinesterase was measured in diaphragm and brain of tabun-poisoned rats. The results showed that the reactivating efficacy of two recently developed oximes (K727 and K733) does not achieve the level of the reactivation of tabun-inhibited acetylcholinesterase induced by oxime K203 and trimedoxime. While all oximes studied were able to increase the activity of tabun-inhibited acetylcholinesterase in diaphragm, oxime K733 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied roughly corresponds to their reactivating efficacy. While both recently developed oximes were able to reduce acute toxicity of tabun less than 1.5-fold, another original oxime K203 and commonly used trimedoxime reduced the acute toxicity of tabun almost two times. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of oxime K203 and trimedoxime, and therefore, they are not suitable for their replacement of commonly used oximes for the antidotal treatment of acute tabun poisoning.

  11. A comparison of the reactivating and therapeutic efficacy of newly developed oximes (K347, K628) with commonly used oximes (obidoxime, HI-6) against tabun in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Kuca, Kamil; Musilek, Kamil

    2010-07-01

    The potency of newly developed reactivators of nerve agent-inhibited acetylcholinesterase (K347, K628) in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, the oxime HI-6), using in vivo methods. Studies that determined the percentage of reactivation of tabun-inhibited blood and tissue acetycholinesterase in poisoned rats showed that the reactivating efficacy of both newly developed oximes is comparable with the oxime HI-6, but it is significantly lower than the reactivating effects of obidoxime. The monopyridinium oxime, K347, was also found to be able to reduce lethal toxic effects in tabun-poisoned mice, while the therapeutic efficacy of another newly developed bispyridinium oxime, K628, was negligible. The therapeutic efficacy of K347 was higher than the potency of the oxime, HI-6, but it was lower than the therapeutic effects of obidoxime. Thus, the reactivating and therapeutic potency of both newly developed oximes (K347, K628) was not more effective then currently available oximes, and therefore, they are not suitable for the replacement of commonly used oximes (especially obidoxime) for the treatment of acute tabun poisoning.

  12. Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience

    Directory of Open Access Journals (Sweden)

    Hirano R

    2016-10-01

    Full Text Available Ryuichi Hirano,1 Yuichi Sakamoto,2 Junichi Kitazawa,2 Shoji Yamamoto,1 Naoki Tachibana2 1Department of Pharmacy, 2Laboratory Medicine and Blood Transfusion, Aomori Prefectural Central Hospital, Aomori-shi, Japan Background: Vancomycin (VCM requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP on attaining target VCM trough concentrations and pharmacokinetics (PK/pharmacodynamics (PD parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA infections. Materials and methods: The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation and from April 2012 to December 2014 (postimplementation, 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51. In 65 patients (pre, n=15; post, n=50, 24-hour area under the ­concentration–time curve (AUC 0–24 h/minimum inhibitory concentration (MIC ratios were calculated. Results: Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33. The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL was significantly higher during postimplementation (84%, 43/51 than during preimplementation (39%, 11/28 (P<0.01. The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400 was significantly higher during postimplementation (84%, 42/50 than during preimplementation (53%, 8/15; P=0.013. There were

  13. [(11)C]DAC-PET for noninvasively monitoring neuroinflammation and immunosuppressive therapy efficacy in rat experimental autoimmune encephalomyelitis model.

    Science.gov (United States)

    Xie, Lin; Yamasaki, Tomoteru; Ichimaru, Naotsugu; Yui, Joji; Kawamura, Kazunori; Kumata, Katsushi; Hatori, Akiko; Nonomura, Norio; Zhang, Ming-Rong; Li, Xiao-Kang; Takahara, Shiro

    2012-03-01

    Neuroimaging measures have potential for monitoring neuroinflammation to guide treatment before the occurrence of significant functional impairment or irreversible neuronal damage in multiple sclerosis (MS). N-Benzyl-N-methyl-2-(7-[(11)C]methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([(11)C]DAC), a new developed positron emission tomography (PET) probe for translocator protein 18 kDa (TSPO), has been adopted to evaluate the neuroinflammation and treatment effects of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [(11)C]DAC-PET enabled visualization of neuroinflammation lesion of EAE by tracing TSPO expression in the spinal cords; the maximal uptake value reached in day 11 and 20 EAE rats with profound inflammatory cell infiltration compared with control, day 0 and 60 EAE rats. Biodistribution studies and in vitro autoradiography confirmed these in vivo imaging results. Doubling immunohistochemical studies showed the infiltration and expansion of CD4+ T cells and CD11b+ microglia; CD68+ macrophages were responsible for the increased TSPO levels visualized by [(11)C]DAC-PET. Furthermore, mRNA level analysis of the cytokines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed that TSPO+/CD4 T cells, TSPO+ microglia and TSPO+ macrophages in EAE spinal cords were activated and secreted multiple proinflammation cytokines to mediate inflammation lesions of EAE. EAE rats treated with an immunosuppressive agent: 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diolhydrochloride (FTY720), which exhibited an absence of inflammatory cell infiltrates, displaying a faint radioactive signal compared with the high accumulation of untreated EAE rats. These results indicated that [(11)C] DAC-PET imaging is a sensitive tool for noninvasively monitoring the neuroinflammation response and evaluating therapeutic interventions in EAE.

  14. Differences in effectiveness of intensive programs of treatment for neurotic and personality disorders. Is it worth to monitor the effectiveness of the therapeutic team?

    Directory of Open Access Journals (Sweden)

    Styła, Rafał

    2014-02-01

    Full Text Available Objectives. To test whether three different intensive programs of treatment for neurotic and personality disorders are effective in decreasing neurotic symptoms and traits of neurotic personality and whether there are differences between them in clinical outcome. Method: The sample consisted of 105 patients (83% female, mean age 35 diagnosed with neurosis and personality disorders that were treated in three therapeutic wards under routine inpatient conditions. The therapeutic programs are designed for patients with neurotic and personality disorders. They consist of 6-12 weeks of approximately 5 hours of eclectic group treatment (group psychotherapy, psychodrama, psychoeducation etc.. Participants filled in Symptoms’ Questionnaire KS-II, and Neurotic Personality Questionnaire KON-2006 at the beginning and at the end of the course of psychotherapy. Results. The treatment proved to be effective in diminishing neurotic symptoms (d Cohen=0.56. More detailed analysis revealed that there was a significant interaction between the three analysed therapeutic wards and the effectiveness (.2=0.09. The treatments offered in two institutions were effective (d Cohen=0.80 while one of the programs did not lead to significant improvement of the patients. None of the therapeutic wards proved to be effective in changing the neurotic personality traits. Conlusions. There are significant differences in effectiveness of the intensive programs of treatment for neurotic and personality disorders. In the light of the literature, one can assume that the differences are more connected with the characteristics of therapeutic teams than with the methods used. The need for standard methods of effectiveness monitoring is discussed.

  15. Therapeutic Exercise and Hypertension

    African Journals Online (AJOL)

    Nekky Umera

    focus of this review is to discuss the therapeutic efficacy of exercise on ... as high level of sodium in diet, alcohol consumption, obesity, physical inactivity, age, and .... idiopathic (essential) hypertension, there are two modes or approaches.

  16. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Vaughan-Williams Charles H

    2012-12-01

    suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

  17. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

    Science.gov (United States)

    Vaughan-Williams, Charles H; Raman, Jaishree; Raswiswi, Eric; Immelman, Etienne; Reichel, Holger; Gate, Kelly; Knight, Steve

    2012-12-28

    Zulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

  18. A clinical study on the efficacy of natural therapeutic factors in Băile Tuşnad for the rehabilitation of post-stroke patients

    Directory of Open Access Journals (Sweden)

    Gabriela Dogaru

    2017-02-01

    Full Text Available Introduction. Stroke is one of the main causes of morbidity and mortality worldwide. Hypotonic carbonated mineral waters in Băile Tușnad are used for their peripheral and cerebral vasodilator effects in the prophylaxis, therapy and rehabilitation of cardiovascular patients. Objectives. The aim of the clinical study was to assess the efficacy of natural therapeutic factors in Băile Tușnad for continuing the rehabilitation of post-stroke patients in a spa and climatic resort for the treatment of cardiovascular diseases. Methods. The study included 30 patients with a history of stroke, aged between 56 and 89 years, with a mean age of 69 years, at the Facility Treatment of the Tușnad Spa Complex SA, in the period April-December 2014. The clinical study was a prospective longitudinal analysis. Of all 30 patients, 50% had ischemic stroke, 43% transient cerebral ischemic attack, and 7% hemorrhagic stroke. Hemiparesis was the most frequent clinical sign, followed by coordination, balance and gait disorders. Patients attended rehabilitation treatment consisting of kinesiotherapy, carbonated mineral water baths for 15 minutes, aerotherapy for 30 minutes daily, massotherapy, performed daily for 16 days. Each patient was clinically assessed before and after treatment based on the TINETTI Balance Scale, the 10-m walk test, the Motor Assessment Scale, the BARTHEL Index, adverse reactions. Results. At the end of treatment, an improvement in the walking speed, a statistically significant improvement in the quality of gait were observed, p < 0.05. Statistically significant results p<0.05 were also obtained for balance. On the Motor Assessment Scale, by comparing the means before and after treatment with the paired T test, a statistically significant value p<0.05 was obtained. When evaluating the patients’ performance for 10 activities of daily living depending on the need for external assistance, using the Barthel Index, the value of p <0.05 was

  19. Impact of therapeutic drug monitoring of antiretroviral drugs in routine clinical management of patients infected with human immunodeficiency virus and related health care costs: a real-life study in a large cohort of patients

    Directory of Open Access Journals (Sweden)

    Perrone V

    2014-07-01

    Full Text Available Valentina Perrone,1 Dario Cattaneo,1 Sonia Radice,1 Diego Sangiorgi,2 Augusto B Federici,3 Maria Rita Gismondo,4 Massimo Medaglia,5 Valeria Micheli,4 Stefania Vimercati,5 Enza Pallone,6 Luca Degli Esposti,2 Emilio Clementi1,71Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, L Sacco University Hospital, University of Milan, Milan, 2CliCon Srl, Health, Economics and Outcomes Research, Ravenna, 3Hematology and Transfusion Medicine, Department of Clinical Sciences and Community Health, 4Clinical Microbiology Virology and Diagnosis of Bioemergency, 5Pharmaceutical Department, 6Quality Clinical Risk and Accreditation Unit, L Sacco University Hospital, Milan, 7Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, ItalyBackground: Highly active antiretroviral therapy (HAART has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV. Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness.Methods: A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other.Results: The cohort consisted of 5,347 patients (3,861 males and 1,486 females of mean age 43.9±12.5 years. We found

  20. Novel insights in the fecal egg count reduction test for monitoring drug efficacy against soil-transmitted helminths in large-scale treatment programs.

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    Bruno Levecke

    2011-12-01

    Full Text Available BACKGROUND: The fecal egg count reduction test (FECRT is recommended to monitor drug efficacy against soil-transmitted helminths (STHs in public health. However, the impact of factors inherent to study design (sample size and detection limit of the fecal egg count (FEC method and host-parasite interactions (mean baseline FEC and aggregation of FEC across host population on the reliability of FECRT is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: A simulation study was performed in which FECRT was assessed under varying conditions of the aforementioned factors. Classification trees were built to explore critical values for these factors required to obtain conclusive FECRT results. The outcome of this analysis was subsequently validated on five efficacy trials across Africa, Asia, and Latin America. Unsatisfactory (<85.0% sensitivity and specificity results to detect reduced efficacy were found if sample sizes were small (<10 or if sample sizes were moderate (10-49 combined with highly aggregated FEC (k<0.25. FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The most discriminatory study design required 200 subjects independent of STH status (including subjects wh