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Sample records for achieve therapeutic concentrations

  1. Individualizing amikacin regimens: accurate method to achieve therapeutic concentrations.

    PubMed

    Zaske, D E; Cipolle, R J; Rotschafer, J C; Kohls, P R; Strate, R G

    1991-11-01

    Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (greater than 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.

  2. Program for Area Concentration Achievement Testing.

    ERIC Educational Resources Information Center

    Golden, Anthony J.

    The Program for Area Concentration Achievement Testing (PACAT) produces the cooperative assessment instrument known as the Area Concentration Achievement Test (ACAT). The ACAT uses a model designed specifically to measure curricular strengths and weaknesses and to provide this information at the departmental level. PACAT has developed 57…

  3. Project for Area Concentration Achievement Testing (PACAT).

    ERIC Educational Resources Information Center

    Austin Peay State Univ., Clarksville, TN.

    The history of the Project for Area Concentration Achievement Testing (PACAT), a university based national curriculum assessment project, is described in this report. The project performs surveys of academic curricula by content area, collects examination items from the faculty of participating departments, and constructs, distributes, and scores…

  4. Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population.

    PubMed

    Gavaler, Judith S

    2002-02-01

    The assumption that estradiol (E2) concentrations are reliably increased to therapeutic levels in postmenopausal women receiving hormone replacement therapy (HRT) has not been explicitly tested. Nor have factors that may modulate the E2 levels achieved been evaluated. The author examined E2 concentrations in a multiracial study population of 309 postmenopausal women treated with oral HRT and observed that 51.1% had achieved estradiol levels of at least 45 pg/ml (achievers). The odds of being an achiever were significantly elevated among non-Caucasian women by a HRT dose greater than 0.625 mg, current moderate drinking, and increasing duration of HRT use. The odds were significantly decreased by having a high school education or less and increasing time since last HRT dose. White postmenopausal women had significantly reduced odds of being an achiever, and both a dose of less than 0.625 mg and a dose equal to 0.625 mg significantly reduced the odds of being an achiever. Increasing body mass index and menopause duration were both associated with lower odds. This report demonstrates not only that women treated with HRTdo not all achieve therapeutic levels of estradiol but also that factors can be identified that modulate the E2 concentration achieved in response to HRT administration.

  5. Mass or molar? Recommendations for reporting concentrations of therapeutic drugs.

    PubMed

    Jones, Graham R D; Bryant, Stewart; Fullinfaw, Robert; Ilett, Ken; Miners, John O; Morris, Raymond G; Doogue, Matthew P

    2013-04-15

    A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Royal College of Pathologists of Australasia and Royal Australasian College of Physicians recommends the following: *mass units should be used for reporting therapeutic drug concentrations in Australia and New Zealand; and the litre (L) should be used as the denominator when expressing concentration. Examples of these units are mg/L and μg/L Exceptions to these principles include: *drugs for which there is current uniformity of reporting and supporting information using molar units, notably lithium (mmol/L) and methotrexate (μmol/L); *drugs that are also present as endogenous substances, where the units used routinely should continue to be used. This applies to many substances, including minerals (eg, iron; μmol/L), vitamins (eg, vitamin D; nmol/L) and hormones (eg, thyroxine; pmol/L). *drugs for which the denominator is not a 198 of fluid and there is international uniformity of reporting (eg, thiopurine metabolites; per 109 red blood cells). These recommendations relate to drugs that are used therapeutically, whether measured for therapeutic drug monitoring purposes or for assessment of overdose. Other substances, such as drugs of misuse, heavy metals or environmental toxins, were not considered by the WP and are thus not covered by this document. These recommendations should also be applied to other supporting documentation such as published guidelines, journal articles and websites. The implementation of these recommendations in New Zealand is subject to local confirmation.

  6. Achieving high mass-throughput of therapeutic proteins through parvovirus retentive filters.

    PubMed

    Bolton, Glen R; Basha, Jonida; Lacasse, Daniel P

    2010-01-01

    Parvovirus retentive filters that assure removal of viruses and virus-like particles during the production of therapeutic proteins significantly contribute to total manufacturing costs. Operational approaches that can increase throughput and reduce filtration area would result in a significant cost savings. A combination of methods was used to achieve high throughputs of an antibody or therapeutic protein solution through three parvovirus retentive filters. These methods included evaluation of diatomaceous earth or size-based prefilters, the addition of additives, and the optimization of protein concentration, temperature, buffer composition, and solution pH. An optimum temperature of 35°C was found for maximizing throughput through the Virosart CPV and Viresolve Pro filters. Mass-throughput values of 7.3, 26.4, and 76.2 kg/m(2) were achieved through the Asahi Planova 20N, Virosart CPV, and Viresolve Pro filters, respectively, in 4 h of processing. Mass-throughput values of 73, 137, and 192 kg/m(2) were achieved through a Millipore Viresolve Pro filter in 4.0, 8.8, and 22.1 h of processing, respectively, during a single experiment. However, large-scale parvovirus filtration operations are typically controlled to limit volumetric throughput to below the level achieved during small-scale virus spiking experiments. The virus spike may cause significant filter plugging, limiting throughput. Therefore newer parvovirus filter spiking strategies should be adopted that may lead to more representative viral clearance data and higher utilization of large-scale filter capacity.

  7. Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

    PubMed

    Procházka, Václav; Jurčíková, Jana; Laššák, Ondrej; Vítková, Kateřina; Pavliska, Lubomír; Porubová, Ludmila; Buszman, Piotr P; Krauze, Agata; Fernandez, Carlos; Jalůvka, František; Špačková, Iveta; Lochman, Ivo; Jana, Dvořáčková; Merfeld-Clauss, Stephanie; March, Keith L; Traktuev, Dmitry O; Johnstone, Brian H

    2016-01-01

    Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent

  8. Conditions for achieving ideal and Lambertian symmetrical solar concentrators

    SciTech Connect

    Luque, A.; Lorenzo, E.

    1982-10-15

    Symmetrical bidimensional concentrators are discussed, and it is proven that for a given source's angular extension a curve exists that divides the plane into two regions. No ideal concentrator can be found with its edges on the outer region and no Lambertian concentrator can be found with its edges on the inner region. A consequence of this theorem is that a concentrator is forced to cast some of the incident energy outside the collector to ensure its obtaining the maximum power.

  9. Conditions for achieving ideal and Lambertian symmetrical solar concentrators.

    PubMed

    Luque, A; Lorenzo, E

    1982-10-15

    In this paper we are concerned with symmetrical bidimensional concentrators, and we prove that for a given source's angular extension a curve exists that divides the plane into two regions. No ideal concentrator can be found with its edges on the outer region and no Lambertian concentrator can be found with its edges on the inner region. A consequence of this theorem is that a concentrator is forced to cast some of the incident energy outside the collector to ensure its obtaining the maximum power.

  10. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    PubMed

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally.

  11. [Update of planning tables of cholesterol-lowering therapy orientated to achieve LDL therapeutic targets].

    PubMed

    Masana, Luis; Plana, Núria

    2015-01-01

    This is the third update of a planning-table for use in cholesterol-lowering therapy, so as to obtain LDLc objectives. This is an easy to use laptop tool to help choose the best statin or combination therapy (statin plus ezetimibe) depending on the current LDL concentration of the patient, and the LDLc objective to achieve. It is based on a colour code that indicates the drugs that are efficient enough to help patients to achieve their LDL goal. Along with the table, recommendations are given for the best strategy in order to implement the optimal therapy in a maximum of two clinical encounters.

  12. Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence

    PubMed Central

    García, María Luisa Gutiérrez; Blasco-Algora, Sara; Fernández-Rodríguez, Conrado M

    2015-01-01

    Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken. PMID:26229395

  13. HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements

    PubMed Central

    Mielcarek, Michal; Zielonka, Daniel; Carnemolla, Alisia; Marcinkowski, Jerzy T.; Guidez, Fabien

    2015-01-01

    For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to chromatin condensation followed by transcriptional repression. HDACs are divided into distinct classes: I, IIa, IIb, III, and IV, on the basis of size and sequence homology, as well as formation of distinct repressor complexes. Implications of HDACs in many diseases, such as cancer, heart failure, and neurodegeneration, have identified these molecules as unique and attractive therapeutic targets. The emergence of HDAC4 among the members of class IIa family as a major player in synaptic plasticity raises important questions about its functions in the brain. The characterization of HDAC4 specific substrates and molecular partners in the brain will not only provide a better understanding of HDAC4 biological functions but also might help to develop new therapeutic strategies to target numerous malignancies. In this review we highlight and summarize recent achievements in understanding the biological role of HDAC4 in neurodegenerative processes. PMID:25759639

  14. Gaps Between Aims and Achievements in Therapeutic Modification of Neuronal Damage ("Neuroprotection").

    PubMed

    Wiendl, Heinz; Elger, Christian; Förstl, Hans; Hartung, Hans-Peter; Oertel, Wolfgang; Reichmann, Heinz; Schwab, Stefan

    2015-04-01

    The term "neuroprotection" is often misused, overused, or misunderstood. A reasonable definition of neuroprotection refers to the preservation of "neuronal structure and/or function." Although our knowledge about the cellular and molecular mechanisms of neurodegeneration has expanded, experimental systems and animal models that mimic the process or allow translation into clinical success remain limited. This editorial discusses reasons for this gap and strategies to close it. Experimental models can only mirror certain aspects of disease mechanisms in humans. Therefore, findings in these models need to be linked with patient data to improve real-life relevance. Successful neuroprotection depends on finding the right "window of opportunity" which varies from very short (stroke) to very long (Alzheimer's disease), necessitating the need to focus on strategies for very early disease recognition. This need challenges the strategies to be chosen, trial approaches and methodologies, and the allocation of resources. Additionally, outcome measures are often not well suited to assess neuroprotection. To this end, surrogate measures, including biomarkers, are useful endpoints to demonstrate evidence of target directed therapeutic utility. Finally, studies have shown that neuroprotection is not likely to succeed when targeting only one pathway. These obstacles have reduced the level of enthusiasm for neuroprotection in certain disease areas (e.g., stroke). Academia, industry, regulatory authorities, funding agencies and patient organizations have to cooperate to a greater extent in order to overcome these impediments and to encourage nonclassical concepts. These concepts will be interdisciplinary in order to achieve meaningful disease modification.

  15. Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris.

    PubMed

    Pine, M; Favrot, L; Smith, S; McDonald, K; Chidsey, C A

    1975-11-01

    The therapeutic response to propranolol was evaluated in patients with documented coronary artery disease at doses varying from 40 to 320 mg/day. Therapeutic response was quantified by evaluating exercise performance on a treadmill and then related to plasma propranolol concentration. Plasma propranolol was defined in terms of beta-adrenergic blockade by comparison with dose (concentration) response curves in normal subjects. Individual therapeutic benefit occurred at doses which averaged 144 +/- 21 mg/day and at concentrations which averaged 30 +/- 7 ng/ml. There was a wide variation between both dose and concentration among the patients at maximum therapeutic response, but when the plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 to 98% of total blockade. Despite the increased exercise performance in these patients, the double product of heart rate and systolic blood pressure was always less, suggesting either an alteration of the relation between myocardial oxygen consumption and the double product during propranolol or a reduction on oxygen delivery to the myocardium as the result of beta-adrenergic blockade of the coronary vasculature.

  16. Effects of Learning Styles and Interest on Concentration and Achievement of Students in Mobile Learning

    ERIC Educational Resources Information Center

    Li, Xiaojie; Yang, Xianmin

    2016-01-01

    Learning concentration deserves in-depth investigation in the field of mobile learning. Therefore, this study examined the interaction effects of learning styles and interest on the learning concentration and academic achievement of students who were asked to learn conceptual knowledge via their mobile phones in a classroom setting. A total of 92…

  17. Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.

    PubMed

    Roberts, J A; Stove, V; De Waele, J J; Sipinkoski, B; McWhinney, B; Ungerer, J P J; Akova, M; Bassetti, M; Dimopoulos, G; Kaukonen, K-M; Koulenti, D; Martin, C; Montravers, P; Rello, J; Rhodes, A; Starr, T; Wallis, S C; Lipman, J

    2014-05-01

    The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.

  18. Development of macrolide-resistant Campylobacter in broilers administered subtherapeutic or therapeutic concentrations of tylosin.

    PubMed

    Ladely, Scott R; Harrison, Mark A; Fedorka-Cray, Paula J; Berrang, Mark E; Englen, Mark D; Meinersmann, Richard J

    2007-08-01

    The use of antimicrobials in food animal production, particularly those commonly used to treat infections in humans, has become a source of debate in recent years. However, limited data are available regarding the development of resistance following the subtherapeutic or therapeutic administration of antimicrobials in animal production. The objective of this study was to evaluate the effect of the administration of therapeutic and subtherapeutic concentrations of tylosin on the erythromycin susceptibility of Campylobacter jejuni and Campylobacter coli isolated from the ceca of treated broilers. In three replicated studies, day-of-hatch chicks were exposed to macrolide-susceptible C. jejuni or C. coli. At 2 weeks of age, tylosin was administered at subtherapeutic (22 ppm, continuously in the diet) or therapeutic concentrations (529 ppm, in the drinking water for 5 days). Broilers were sacrificed weekly. Total and erythromycin-resistant Campylobacter spp. were enumerated from individual ceca plus cecal contents. Overall erythromycin resistance was observed at a higher frequency (P < 0.01) among C. coli isolates (70.8%) than among C. jejuni isolates (36.8%) following tylosin administration. Across Campylobacter species, erythromycin resistance was observed at a higher frequency (P < 0.001) when tylosin was administered at subtherapeutic (62.7%) than at therapeutic (11.4%) concentrations. Subtherapeutic administration resulted in the recovery of 83.3 and 56.1% erythromycin-resistant isolates compared with only 33.3 and 7.9% of the isolates expressing erythromycin resistance following the administration of therapeutic concentrations for C. coli and C. jejuni, respectively. Further studies are needed to determine the factors involved in the apparent difference in the acquisition of macrolide resistance in C. coli compared with C. jejuni.

  19. The effect of environmental and therapeutic concentrations of antibiotics on nitrate reduction rates in river sediment.

    PubMed

    Yan, Chen; Dinh, Quoc Tuc; Chevreuil, Marc; Garnier, Josette; Roose-Amsaleg, Céline; Labadie, Pierre; Laverman, Anniet M

    2013-07-01

    The use of antibiotics in both human and veterinary medicine has led to increased presence of these compounds and antibiotic resistance in the environment. In this study, the effect of low, environmentally relevant (therapeutic (>mg L(-1)) concentrations of vancomycin (VA), flumequine (FLU), and sulfamethoxazole (SMX) on nitrate reduction rates was studied in river sediments. Nitrate reduction rates were determined by supplying intact sediments for several weeks with both nitrate and antibiotics (ng L(-1), μg L(-1), and mg L(-1) concentrations), including a non-amended control. Furthermore the concentrations of the three investigated antibiotics were measured in the initial (natural) sediments and the sediments supplied with the antibiotics. The antibiotic concentrations in the sediments decreased (on average 62% for FLU and 93% for SMX) during the experiments, indicating loss of antibiotics due to sorption or (bio) degradation. Nitrate reduction rates were not affected by environmental concentrations of VA, FLU and SMX. FLU and SMX only partially inhibited nitrate reduction rates at high, therapeutic concentrations by 41 and 39% respectively. The three tested antibiotics significantly enhanced the production of nitrite, an intermediate in dissimilatory nitrate reduction. Nitrite production increased 1.9 and 1.4 fold for environmental VA concentrations (107 and 187 μg L(-1) respectively), application of 58 mg L(-1) SMX resulted in a 7.5 fold increase and augmented 16 and 8.5 fold in the presence of respectively 13 μg L(-1) and 52 mg L(-1) FLU. Even though inhibition of nitrate reduction rates was observed at therapeutic antibiotic concentrations, nitrate reduction proceeded under all experimental conditions, indicating the presence of resistance toward these antibiotics among the nitrate reducing bacteria. The accumulation of nitrite suggests that the nitrite reduction step was more affected than the overall nitrate reduction process.

  20. Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

    PubMed

    Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

    2016-10-21

    Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427.

  1. Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder.

    PubMed

    Ulrich, S; Neuhof, S; Braun, V; Meyer, F P

    1998-09-01

    Although several studies have been performed on the serum level-therapeutic effect relationship of neuroleptic drugs, the application of therapeutic drug-monitoring of neuroleptics is still a matter of controversy. Until now, haloperidol provided the most promising results. For this reason, an investigation of the dependence of clinical improvement on haloperidol serum levels was conducted in an acute psychiatric ward (Landeskrankenhaus Bernburg). In an open clinical trial haloperidol serum levels were measured in 57 acute schizophrenic patients for at least three weeks and correlated with clinical outcome (percent change of Brief Psychiatric Rating Scale, BPRS). A bisigmoidal model was used for data analysis. After three weeks of treatment, the major result proved to be a significant relationship between haloperidol serum level and therapeutic effect with pseudo-r2=0.316 and p=0.0031. Clinical improvement is enhanced by increasing haloperidol concentration up to about 10 ng/ml. It attains a maximum at about 10 ng/ml and decreases at haloperidol serum levels in a range of 10 ng/ml to 50 ng/ml. A simulation of this dependence of clinical improvement on serum levels, mediated by the variable dose design, can be excluded because of the results of a retrospective analysis of dosing behavior. Further evidence is thus provided for the dependence of therapeutic effect on the serum haloperidol concentration in acute schizophrenia. For practical application the position of a therapeutic window can be defined by a lower threshold level of about 5 ng/ml and an upper threshold of about 17 ng/ml. However, a maximal therapeutic effect is assured at 10 ng/ml. This should be the target value in serum level-guided dose adjustments.

  2. Does It Matter Where Poor Kids Live? A Look at Concentrated Poverty and Achievement.

    ERIC Educational Resources Information Center

    Schellenberg, Stephen J.

    This study sought to separate the effect of concentrated poverty on students' academic achievement and to develop a simple method for demonstrating that effect. The study was conducted in a midwestern urban school district with characteristics particularly suitable for answering these questions. It used two years worth of data on elementary school…

  3. Strategic administration of enrofloxacin in poultry to achieve higher maximal serum concentrations.

    PubMed

    Sumano, L H; Gutierrez, O L; Zamora, Q M

    2003-03-01

    To achieve a higher maximal serum concentration (Cs(max)) of enrofloxacin after oral administration of 10mg/kg/day of three commercial preparations of enrofloxacin to chickens, two concentrations of the drug were tested (0.1 and 0.2%), under controlled laboratory conditions. A single oral bolus dose was delivered directly into the proventriculus of each of 240 chickens, which were equally divided into six groups: three received the customary concentration (0.1%), and three received the higher concentration. A quantitative/qualitative microbiological analytical method to determine serum concentrations of enrofloxacin and a software program to obtain pharmacokinetic variables, revealed that time vs. concentration relationships best fitted double peak shape curves, Cs(max1) and Cs(max2). Statistically significant (P>0.01) increments were obtained when 0.2% enrofloxacin oral solutions from the three different commercial preparations were administered. The increments ranged from 175% to 338% for Cs(max1) and 69% to 342% for Cs(max2). Optimal bactericidal concentrations of enrofloxacin are usually twice the value of their minimal inhibitory concentration. Although clinical trials are now required, it would appear that increments in the serum concentration of enrofloxacin may reduce to the rate at which bacterial resistance occurs and so increase clinical efficacy without affecting the cost per treatment.

  4. Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing.

    PubMed

    Liu, Jia; Shui, Sai-Lan

    2016-12-28

    The advent of site-specific nucleases, particularly CRISPR/Cas9, provides researchers with the unprecedented ability to manipulate genomic sequences. These nucleases are used to create model cell lines, engineer metabolic pathways, produce transgenic animals and plants, perform genome-wide functional screen and, most importantly, treat human diseases that are difficult to tackle by traditional medications. Considerable efforts have been devoted to improving the efficiency and specificity of nucleases for clinical applications. However, safe and efficient delivery methods remain the major obstacle for therapeutic gene editing. In this review, we summarize the recent progress on nuclease delivery methods, highlight their impact on the outcomes of gene editing and discuss the potential of different delivery approaches for therapeutic gene editing.

  5. The enhancement of antibody concentration and achievement of high cell density CHO cell cultivation by adding nucleoside.

    PubMed

    Takagi, Yasuhiro; Kikuchi, Takuya; Wada, Ryuta; Omasa, Takeshi

    2017-03-02

    Recently, with the dramatic increase in demand for therapeutic antibodies, Chinese hamster ovary (CHO) cell culture systems have made significant progress in recombinant antibody production. Over the past two decades, recombinant antibody productivity has been improved by more than 100-fold. Medium optimization has been identified as an important key approach for increasing product concentrations. In this study, we evaluated the effects of deoxyuridine addition to fed-batch cultures of antibody-expressing CHO cell lines. Furthermore, we investigated the effects of combined addition of deoxyuridine, thymidine, and deoxycytidine. Our results suggest that addition of these pyrimidine nucleosides can increase CHO cell growth, with no significant change in the specific production rate. As a result of the increased cell growth, the antibody concentration was elevated and we were able to achieve more than 9 g/L during 16 days of culture. Similar effects of nucleoside addition were observed in fed-batch cultures of a Fab fragment-expressing CHO cell line, and the final Fab fragment concentration was more than 4 g/L. This nucleoside addition strategy could be a powerful platform for efficient antibody production.

  6. Concomitant Raman spectroscopy and dynamic light scattering for characterization of therapeutic proteins at high concentrations.

    PubMed

    Zhou, Chen; Qi, Wei; Lewis, E Neil; Carpenter, John F

    2015-03-01

    A Raman spectrometer and dynamic light scattering system were combined in a single platform (Raman-DLS) to provide concomitant higher order structural and hydrodynamic size data for therapeutic proteins at high concentration. As model therapeutic proteins, we studied human serum albumin (HSA) and intravenous immunoglobulin (IVIG). HSA concentration and temperature interval during heating did not affect the onset temperatures for conformation perturbation or aggregation. The impact of pH on thermal stability of HSA was tested at pHs 3, 5, and 8. Stability was the greatest at pH 8, but distinct unfolding and aggregation behaviors were observed at the different pHs. HSA structural transitions and aggregation kinetics were also studied in real time during isothermal incubations at pH 7. In a forced oxidation study, it was found that hydrogen peroxide (H2O2) treatment reduced the thermal stability of HSA. Finally, the structure and thermal stability of IVIG were studied, and a comprehensive characterization of heating-induced structural perturbations and aggregation was obtained. In conclusion, by providing comprehensive data on protein tertiary and secondary structures and hydrodynamic size during real-time heating or isothermal incubation experiments, the Raman-DLS system offers unique physical insights into the properties of high-concentration protein samples.

  7. Achieving optimum carrier concentrations in p-doped SnS thermoelectrics.

    PubMed

    Bhattacharya, Sandip; Gunda, N S Harsha; Stern, Robin; Jacobs, Stéphane; Chmielowski, Radoslaw; Dennler, Gilles; Madsen, Georg K H

    2015-04-14

    Tin(II)sulfide, SnS, is a commercially viable and environmentally friendly thermoelectric material. Recently it was shown how the carrier concentration and the thermoelectric power factor can be optimized by Ag-doping in a sulphur rich environment. Theoretical calculations lead to a fairly accurate estimation of the carrier concentration, whereas the potential of doping with Li(+) is strongly overestimated. Two principally ubiquitous effects that can result in decreasing the hole concentration, namely the formation of coupled defect complexes and oxidation of the dopant, are discussed as possible origins of this disagreement. It is shown that oxidation limits the chemical potential of Li beyond that already set by the formation of Li2S. This work serves as a comprehensive guide to achieve an efficient p-doped SnS thermoelectric material.

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

    PubMed

    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 < 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P < 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P < 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (P < 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure

  9. Magnetic Heating of Nanoparticles: The Importance of Particle Clustering to Achieve Therapeutic Temperatures.

    PubMed

    Pearce, John; Giustini, Andrew; Stigliano, Robert; Jack Hoopes, P

    2013-02-01

    Hyperthermia therapy for cancer treatment seeks to destroy tumors through heating alone or combined with other therapies at elevated temperatures between 41.8 and 48 °C. Various forms of cell death including apoptosis and necrosis occur depending on temperature and heating time. Effective tumoricidal effects can also be produced by inducing damage to the tissue vasculature and stroma; however, surrounding normal tissue must be spared to a large extent. Magnetic nanoparticles have been under experimental investigation in recent years as a means to provide a favorable therapeutic ratio for local hyperthermia; however, practical numerical models that can be used to study the underlying mechanisms in realistic geometries have not previously appeared to our knowledge. Useful numerical modeling of these experiments is made extremely difficult by the many orders of magnitude in the geometries: from nanometers to centimeters. What has been missing is a practical numerical modeling approach that can be used to more deeply understand the experiments. We develop and present numerical models that reveal the extent and dominance of the local heat transfer boundary conditions, and provide a new approach that may simplify the numerical problem sufficiently to make ordinary computing machinery capable of generating useful predictions. The objectives of this paper are to place the discussion in a convenient interchangeable classical electromagnetic formulation, and to develop useful engineering approximations to the larger multiscale numerical modeling problem that can potentially be used in experiment evaluation; and eventually, may prove useful in treatment planning. We cast the basic heating mechanisms in the framework of classical electromagnetic field theory and provide calibrating analytical calculations and preliminary experimental results on BNF-Starch(®) nanoparticles in a mouse tumor model for perspective.

  10. A Desired PAR-Achieving Precoder Design for Multiuser MIMO OFDM Based on Concentration of Measure

    NASA Astrophysics Data System (ADS)

    Cha, Hyun-Su; Kim, Dong Ku

    2017-03-01

    For multi-user multiple-input and multiple-output (MIMO) wireless communications in orthogonal frequency di- vision multiplexing systems, we propose a MIMO precoding scheme providing a desired peak-to-average power ratio (PAR) at the minimum cost that is defined as received SNR degradation. By taking advantage of the concentration of measure, we formulate a convex problem with constraint on the desired PAR. Consequently, the proposed scheme almost exactly achieves the desired PAR on average, and asymptotically attains the desired PAR at the 0.001 point of its complementary cumulative distribution function, as the number of subcarriers increases.

  11. Concentric Tube Robots as Steerable Needles: Achieving Follow-the-Leader Deployment.

    PubMed

    Gilbert, Hunter B; Neimat, Joseph; Webster, Robert J

    2015-04-01

    Concentric tube robots can enable new clinical interventions if they are able to pass through soft tissue, deploy along desired paths through open cavities, or travel along winding lumens. These behaviors require the robot to deploy in such a way that the curved shape of its shaft remains unchanged as the tip progresses forward (i.e., "follow-the-leader" deployment). Follow-the-leader deployment is challenging for concentric tube robots due to elastic (and particularly torsional) coupling between the tubes that form the robot. However, as we show in this paper, follow-the-leader deployment is possible, provided that tube precurvatures and deployment sequences are appropriately selected. We begin by defining follow-the-leader deployment and providing conditions that must be satisfied for a concentric tube robot to achieve it. We then examine several useful special cases of follow-the-leader deployment, showing that both circular and helical precurvatures can be employed, and provide an experimental illustration of the helical case. We also explore approximate follow-the-leader behavior and provide a metric for the similarity of a general deployment to a follow-the-leader deployment. Finally, we consider access to the hippocampus in the brain to treat epilepsy, as a motivating clinical example for follow-the-leader deployment.

  12. Concentric Tube Robots as Steerable Needles: Achieving Follow-the-Leader Deployment

    PubMed Central

    Gilbert, Hunter B.; Neimat, Joseph; Webster, Robert J.

    2015-01-01

    Concentric tube robots can enable new clinical interventions if they are able to pass through soft tissue, deploy along desired paths through open cavities, or travel along winding lumens. These behaviors require the robot to deploy in such a way that the curved shape of its shaft remains unchanged as the tip progresses forward (i.e., “follow-the-leader” deployment). Follow-the-leader deployment is challenging for concentric tube robots due to elastic (and particularly torsional) coupling between the tubes that form the robot. However, as we show in this paper, follow-the-leader deployment is possible, provided that tube precurvatures and deployment sequences are appropriately selected. We begin by defining follow-the-leader deployment and providing conditions that must be satisfied for a concentric tube robot to achieve it. We then examine several useful special cases of follow-the-leader deployment, showing that both circular and helical precurvatures can be employed, and provide an experimental illustration of the helical case. We also explore approximate follow-the-leader behavior and provide a metric for the similarity of a general deployment to a follow-the-leader deployment. Finally, we consider access to the hippocampus in the brain to treat epilepsy, as a motivating clinical example for follow-the-leader deployment. PMID:26622208

  13. Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations

    PubMed Central

    Boland, I; Vassal, G; Morizet, J; Terrier-Lacombe, M-J; Valteau-Couanet, D; Kalifa, C; Hartmann, O; Gouyette, A

    1999-01-01

    High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg−1), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 μg h ml−1) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 μg h ml−1). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens. 1999 Cancer Research Campaign PMID:10070870

  14. Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

    PubMed Central

    Almeida, M.B.; Costa-Malaquias, A.; Nascimento, J.L.M.; Oliveira, K.R.; Herculano, A.M.; Crespo-López, M.E.

    2014-01-01

    Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting. PMID:24728211

  15. Concentrations of nandrolone metabolites in urine after the therapeutic administration of an ophthalmic solution.

    PubMed

    Avois, Lidia; Mangin, Patrice; Saugy, Martial

    2007-05-09

    Nandrolone, an anabolic steroid, is used for the treatment of several diseases and is available in various pharmaceutical formulations. The most widely used pharmaceutical formulation is Deca-Durabolin, but other products, such as Keratyl eye drops solution, are also currently administered. Nandrolone is one of the most abused anabolic steroid in sports. Analyses for this anabolic steroid according to the World Anti-Doping Agency (WADA) protocol are based on the identification of the nandrolone two main urinary metabolites which, in humans, are glucuronides of 19-norandrosterone and 19-noretiocholanolone. A positive cut off limit of 2 ng/mL has been set by the anti-doping code for the first metabolite, 19-norandrosterone. In this preliminary study, an eye drops solution (Keratyl) containing a therapeutic dose of a nandrolone sodium sulphate was administered to several male volunteers during 3 days and urines were collected during 3 weeks. Surprisingly, contrary to all expectations, the urinary concentrations measured in urines reached 450 ng/mL and 70 ng/mL for norandrosterone and noretiocholanolone, respectively. Moreover, concentration levels near to 2 ng/mL were found, more than 2 weeks after the last administration, depending on individual metabolism. Inter-variability as well as intra-variability of nandrolone excretion kinetic, regarding this particular administration mode, were also evaluated. Quantification of nandrolone metabolites was performed by GC-MS. The method was previously validated in terms of specificity, precision, linearity, LOD, LOQ, robustness, accuracy and the expanded uncertainty was also evaluated.

  16. The Achievement of Therapeutic Objectives Scale: Interrater Reliability and Sensitivity to Change in Short-Term Dynamic Psychotherapy and Cognitive Therapy

    ERIC Educational Resources Information Center

    Valen, Jakob; Ryum, Truls; Svartberg, Martin; Stiles, Tore C.; McCullough, Leigh

    2011-01-01

    This study examined interrater reliability and sensitivity to change of the Achievement of Therapeutic Objectives Scale (ATOS; McCullough, Larsen, et al., 2003) in short-term dynamic psychotherapy (STDP) and cognitive therapy (CT). The ATOS is a process scale originally developed to assess patients' achievements of treatment objectives in STDP,…

  17. Tafenoquine at therapeutic concentrations does not prolong fridericia-corrected QT interval in healthy subjects

    PubMed Central

    Green, Justin A; Patel, Apurva K; Patel, Bela R; Hussaini, Azra; Harrell, Emma J; McDonald, Mirna J; Carter, Nick; Mohamed, Khadeeja; Duparc, Stephan; Miller, Ann K

    2014-01-01

    Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18–65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200 mg versus placebo (ΔΔQTcF) was <10 milliseconds for all pre-defined time points. The maximum ΔΔQTcF with tafenoquine 1200 mg (n = 50) was 6.39 milliseconds (90% CI 2.85, 9.94) at 72 hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300 mg (n = 48) or 600 mg (n = 52) had no effect on ΔΔQTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine–QTcF concentration–effect relationship demonstrated a shallow slope (0.5 ms/μg mL–1) over a wide concentration range. For moxifloxacin (n = 51), maximum ΔΔQTcF was 8.52 milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization. PMID:24700490

  18. The Three-Layer Concentric Model of Glioblastoma: Cancer Stem Cells, Microenvironmental Regulation, and Therapeutic Implications

    PubMed Central

    Persano, Luca; Rampazzo, Elena; Della Puppa, Alessandro; Pistollato, Francesca; Basso, Giuseppe

    2011-01-01

    Tumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called “hypoxic niche” plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing between Glioblastoma (GBM) stem cells and their niche, defining the theory of three-concentric layers model for GBM mass. According to this model, GBM stem cells reside preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk. Moreover, we discuss the possible clinical implications of the creation of this model for future GBM patient management and novel therapeutic strategies development. PMID:22125441

  19. Concentrating solar power in Europe, the Middle East and North Africa: achieving its potential

    NASA Astrophysics Data System (ADS)

    Pitz-Paal, R.; Amin, A.; Bettzüge, M.; Eames, P.; Fabrizi, F.; Flamant, G.; Garcia Novo, F.; Holmes, J.; Kribus, A.; van der Laan, H.; Lopez, C.; Papagiannakopoulos, P.; Pihl, E.; Smith, P.; Wagner, H.-J.

    2012-10-01

    Concentrating solar power (CSP) is a commercially available renewable energy technology capable of harnessing the immense solar resource in Southern Europe, the Middle East and North Africa (the MENA region), and elsewhere. This paper summarises the findings of a study by the European Academies Science Advisory Council which has examined the current status and development challenges of CSP, and consequently has evaluated the potential contribution of CSP in Europe and the MENA region to 2050. It identifies the actions that will be required by scientists, engineers, policy makers, politicians, business and investors alike, to enable this vast solar resource to make a major contribution to establishing a sustainable energy system. The study concludes that cost reductions of 50-60% in CSP electricity may reasonably be expected in the next 10-15 years, enabling the technology to be cost competitive with fossil-fired power generation at some point between 2020 and 2030. Incorporation of storage delivers added value in enabling CSP to deliver dispatchable power. Incentive schemes will be needed in Europe and MENA countries to enable this point to be achieved. Such schemes should reflect the true value of electricity to the grid, effectively drive R&D, and ensure transparency of performance and cost data.

  20. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    PubMed

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.).

  1. Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism

    PubMed Central

    Gong, Xiaowei; Wang, Haiyan; Yuan, Yadong

    2016-01-01

    The present study aimed to investigate the factors affecting the first therapeutic-target-achieving (TTA) time of warfarin therapy in patients with acute pulmonary embolism (PTE). Between January 2008 and June 2013, patients with PTE confirmed by transpulmonary arterial enhanced computed tomographic pulmonary angiography or pulmonary ventilation perfusion scanning were included in the present study. Data collected included demographic information, history of tobacco and alcohol intake, basic diseases (stable and unstable hypertension, diabetes, heart failure, cancer/cerebral infarction, old myocardial infarction and atrial fibrillation), liver and kidney function, the haemoglobin and platelet count of the blood, international normalized ratio monitoring, warfarin dosage adjustment and medication combinations. Dynamic changes in international normalized ratio, anticoagulant efficacy, and adverse events within 90 days were monitored and analyzed. Univariate analysis demonstrated that the following factors affect the first TTA time: Initial dose, body mass index (BMI), liver function, heart failure, and the administration of levofloxacin, cephalosporins, and blood circulation-activating drugs. Logistic regression analysis revealed that the following were independent factors of the first TTA time: Initial dose, BMI, liver function, heart failure and levofloxacin. Therefore, the results of the present study demonstrated that various factors may affect the first TTA time of warfarin therapy, including the initial dose, BMI, liver function, heart function and concomitant medication. PMID:27698722

  2. Real-time analysis of the effects of toxic, therapeutic and sub-therapeutic concentrations of digitoxin on lung cancer cells.

    PubMed

    Eldawud, R; Stueckle, T A; Manivannan, S; Elbaz, H; Chen, M; Rojanasakul, Y; Dinu, C Z

    2014-09-15

    Digitoxin belongs to a naturally occurring class of cardiac glycosides (CG); digitoxin is clinically approved for heart failure and known for its anti-cancer effects against non-small lung cancer cells (NSCLC). However, concerns associated with its narrow therapeutic index and its concentration-dependent mechanism of action are rising. Thus, before digitoxin implementation in designing and developing safer and more effective CG-based anti-cancer therapies, its pharmacological and safety profiles need to be fully elucidated. In this research we used a combinatorial approach to evaluate the anti-cancer mechanisms of digitoxin in real-time. Our approach employed a non-invasive electric cell impedance sensing technique as a proxy to monitor NSCLC behavior post-exposure to toxic, therapeutic and sub-therapeutic concentrations of the drug. By developing structure-function combinatorial relations we showed that digitoxin targets cancer cells in a time and dose-dependant manner by activating pro-apoptotic and anti-proliferative signaling cascades that results in strengthening cellular adhesion and sequestration of key regulatory proliferation protein from the nucleus.

  3. Freeform lens design to achieve 1000X solar concentration with a parabolic trough reflector

    NASA Astrophysics Data System (ADS)

    Wheelwright, Brian M.; Angel, Roger; Coughenour, Blake

    2014-12-01

    Line-focus parabolic trough mirrors for solar thermal generation cannot produce the high concentration required for concentrating photovoltaic (CPV) systems. We describe a freeform lens array with toroidal symmetry which intercepts the low-concentration line focus to produce a series of elongated, high-concentration foci. The design employs 2D Kӧhler illumination to improve the acceptance angle in one direction. The two-stage concentrator has 1000X average geometric concentration with an acceptance angle of +/-1.49° in the azimuthal direction and +/-0.29° in the elevation direction. Preliminary results of a prototype roll-forming process are shown in thermoplastics and B270 glass.

  4. Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

    PubMed Central

    Lahmann, Carolina; Kramer, Holger B.; Ashcroft, Frances M.

    2015-01-01

    Activating mutations in the Kir6.2 (KCNJ11) subunit of the ATP-sensitive potassium channel cause neonatal diabetes (ND). Patients with severe mutations also suffer from neurological complications. Glibenclamide blocks the open KATP channels and is the treatment of choice for ND. However, although glibenclamide successfully restores normoglycaemia, it has a far more limited effect on the neurological problems. To assess the extent to which glibenclamide crosses the blood-brain barrier (BBB) in vivo, we quantified glibenclamide concentrations in plasma, cerebrospinal fluid (CSF), and brain tissue of rats, control mice, and mice expressing a human neonatal diabetes mutation (Kir6.2-V59M) selectively in neurones (nV59M mice). As only small sample volumes can be obtained from rodents, we developed a highly sensitive method of analysis, using liquid chromatography tandem mass spectrometry acquisition with pseudo-selected reaction monitoring, achieving a quantification limit of 10ng/ml (20nM) glibenclamide in a 30μl sample. Glibenclamide was not detectable in the CSF or brain of rats after implantation with subcutaneous glibenclamide pellets, despite high plasma concentrations. Further, one hour after a suprapharmacological glibenclamide dose was administered directly into the lateral ventricle of the brain, the plasma concentration was twice that of the CSF. This suggests the drug is rapidly exported from the CSF. Elacridar, an inhibitor of P-glycoprotein and breast cancer resistance protein (major multidrug resistance transporters at the BBB), did not affect glibenclamide levels in CSF and brain tissue. We also identified a reduced sensitivity to volatile anaesthetics in nV59M mice and showed this was not reversed by systemic delivery of glibenclamide. Our results therefore suggest that little glibenclamide reaches the central nervous system when given systemically, that glibenclamide is rapidly removed across the BBB when given intracranioventricularly, and that any

  5. Deficits in cognitive function and achievement in Mexican first-graders with low blood lead concentrations.

    PubMed

    Kordas, Katarzyna; Canfield, Richard L; López, Patricia; Rosado, Jorge L; Vargas, Gonzalo García; Cebrián, Mariano E; Rico, Javier Alatorre; Ronquillo, Dolores; Stoltzfus, Rebecca J

    2006-03-01

    Elevated blood lead levels in children are associated with lower scores on tests of cognitive functioning. Recent studies have reported inverse relations between lifetime exposure and intellectual functioning at blood lead concentrations below 10 microg/dL, the Centers for Disease Control and Prevention's (CDC) level of concern. We report associations between blood lead and cognitive performance for first-grade Mexican children living near a metal foundry. Using a cross-sectional design, we examined the relation between children's concurrent blood lead concentrations (mean (SD) 11.4 microg/dL (6.1)) and their performance on 14 tests of global or specific cognitive functions. The blood lead-cognition relations were modeled using both linear and nonlinear methods. After adjustment for covariates, a higher blood lead level was associated with poorer cognitive performance on several cognitive tests. Segmented linear regressions revealed significant effects of lead but only for the segments defined by a concurrent blood lead concentration below 10-14 microg/dL. One implication of these findings is that at the age of 7 years, even in the absence of information on lead exposure in infancy and early childhood, a test result with blood lead < 10 microg/dL should not be considered safe. Together with other recent findings, these results add to the empirical base of support available for evaluating the adequacy of current screening guidelines and for motivating efforts at primary prevention of childhood lead exposure.

  6. Ambient Concentrations of Metabolic Disrupting Chemicals and Children’s Academic Achievement in El Paso, Texas

    PubMed Central

    Clark-Reyna, Stephanie E.; Grineski, Sara E.; Collins, Timothy W.

    2016-01-01

    Concerns about children’s weight have steadily risen alongside the manufacture and use of myriad chemicals in the US. One class of chemicals, known as metabolic disruptors, interfere with human endocrine and metabolic functioning and are of specific concern to children’s health and development. This article examines the effect of residential concentrations of metabolic disrupting chemicals on children’s school performance for the first time. Census tract-level ambient concentrations for known metabolic disruptors come from the US Environmental Protection Agency’s National Air Toxics Assessment. Other measures were drawn from a survey of primary caretakers of 4th and 5th grade children in El Paso Independent School District (El Paso, TX, USA). A mediation model is employed to examine two hypothetical pathways through which the ambient level of metabolic disruptors at a child’s home might affect grade point average. Results indicate that concentrations of metabolic disruptors are statistically significantly associated with lower grade point averages directly and indirectly through body mass index. Findings from this study have practical implications for environmental justice research and chemical policy reform in the US. PMID:27598179

  7. Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations.

    PubMed

    Sumano-López, Héctor; Gutiérrez-Olvera, Lilia; Aguilera-Jiménez, Rita; Gutiérrez-Olvera, Carlos; Jiménez-Gómez, Francisco

    2007-01-01

    To test if capsaicin could improve the bioavailability of ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, CAS 85721-33-1, Bay q 3939) in rats, 0.01, 0.1, 0.5 and 1% capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide, trans-8-methyl-N-vanillyl-6-nonenamide, CAS 404-86-4) dissolved in ethanol and mixed with 20 mg/kg of ciprofloxacin were orally administered to groups of 10 rats each. Control groups were dosed with capsaicin-free, ethanol-containing or ethanol-free ciprofloxacin. Reference intravenous pharmacokinetics of ciprofloxacin was also established. The results revealed that capsaicin increased ciprofloxacin bioavailability by approximately 70% in groups receiving preparations containing capsaicin at a rate of 0.01, 0.1 and 0.5%. Higher concentrations failed to further increase bioavailability. However, capsaicin appears to have little or no impact on the rate of absorption or clearance of ciprofloxacin. Considering that 0.01% or 0.1% capsaicin are unlikely to upset the gastrointestinal tract, it may be worth attempting to study if a similar effect occurs in man, and to evaluate if the addition of capsaicin can be used as a method to increase the area under the curve/minimum inhibitory concentration rate, a key variable to improve clinical efficacy of ciprofloxacin.

  8. Achieving environmentally relevant organochlorine pesticide concentrations in eggs through maternal exposure in Alligator mississippiensis

    USGS Publications Warehouse

    Rauschenberger, R.H.; Wiebe, J.J.; Buckland, J.E.; Smith, Joe T.; Sepulveda, M.S.; Gross, T.S.

    2004-01-01

    Alligator mississippiensis eggs from organochlorine pesticide (OCP) contaminated sites in Florida exhibit high rates of embryonic mortality compared to reference sites (p<0.05). The objective of the present study was to use captive adult alligators to test the hypotheses that maternal exposure to OCPs results in increased OCP concentrations in eggs, and that increased exposure is associated with increased embryonic mortality. A total of 24 adult alligators (8 males and 16 females) were housed in eight pens. Eight females in four pens were dosed with a mixture of p,p'-DDE, toxaphene, dieldrin, and chlordane at a rate of 0.2 ? 0.01 mg/kg/day for 274 ? 8 days. Treated females produced eggs containing higher OCP concentrations (12,814 ? 813 ng/g yolk) than controls (38 ? 4 ng/g yolk). Eggs of treated females exhibited decreased viability (13 ? 22%) as compared to controls (45 ? 20%). Results indicated that 0.6% of administered OCPs were maternally transferred to the eggs of American alligators, and that maternal exposure is associated with decreased egg/embryo viability in this species.

  9. Novel DDR Processing of Corn Stover Achieves High Monomeric Sugar Concentrations from Enzymatic Hydrolysis (230 g/L) and High Ethanol Concentration (10% v/v) During Fermentation

    SciTech Connect

    Chen, Xiaowen; Jennings, Ed; Shekiro, Joe; Kuhn, Erik M.; O'Brien, Marykate; Wang, Wei; Schell, Daniel J.; Himmel, Mike; Elander, Richard T.; Tucker, Melvin P.

    2015-04-03

    Distilling and purifying ethanol, butanol, and other products from second and later generation lignocellulosic biorefineries adds significant capital and operating cost for biofuels production. The energy costs associated with distillation affects plant gate and life cycle analysis costs. Lower titers in fermentation due to lower sugar concentrations from pretreatment increase both energy and production costs. In addition, higher titers decrease the volumes required for enzymatic hydrolysis and fermentation vessels. Therefore, increasing biofuels titers has been a research focus in renewable biofuels production for several decades. In this work, we achieved over 200 g/L of monomeric sugars after high solids enzymatic hydrolysis using the novel deacetylation and disc refining (DDR) process on corn stover. The high sugar concentrations and low chemical inhibitor concentrations from the DDR process allowed ethanol titers as high as 82 g/L in 22 hours, which translates into approximately 10 vol% ethanol. To our knowledge, this is the first time that 10 vol% ethanol in fermentation derived from corn stover without any sugar concentration or purification steps has been reported. Techno-economic analysis shows the higher titer ethanol achieved from the DDR process could significantly reduce the minimum ethanol selling price from cellulosic biomass.

  10. Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

    PubMed

    Park, Wan Beom; Cho, Joo-Youn; Park, Sang-In; Kim, Eun Jung; Yoon, Seonghae; Yoon, Seo Hyun; Lee, Jeong-Ok; Koh, Youngil; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Yu, Kyung-Sang; Kim, Eu Suk; Bang, Su Mi; Kim, Nam Joong; Kim, Inho; Oh, Myoung-Don; Kim, Hong Bin; Song, Sang Hoon

    2016-07-01

    Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (<500 ng/mL) on Day 8. In these patients, the frequency of posaconazole administration was increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was <200 ng/mL. This study shows that increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy.

  11. Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients

    PubMed Central

    Obara, Vitor Yuzo; Zacas, Carolina Petrus; Carrilho, Claudia Maria Dantas de Maio; Delfino, Vinicius Daher Alvares

    2016-01-01

    Objective This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. Methods A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Results Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Conclusion Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged. PMID:28099635

  12. Achieving concentrated graphene dispersions in water/acetone mixtures by the strategy of tailoring Hansen solubility parameters

    NASA Astrophysics Data System (ADS)

    Yi, Min; Shen, Zhigang; Zhang, Xiaojing; Ma, Shulin

    2013-01-01

    Although exfoliating graphite to give graphene paves a new way for graphene preparation, a general strategy of low-boiling-point solvents and high graphene concentration is still highly required. In this study, using the strategy of tailoring Hansen solubility parameters (HSP), a method based on exfoliation of graphite in water/acetone mixtures is demonstrated to achieve concentrated graphene dispersions. It is found that in the scope of blending two mediocre solvents, tailoring the HSP of water/acetone mixtures to approach the HSP of graphene could yield graphene dispersions at a high concentration of up to 0.21 mg ml-1. The experimentally determined optimum composition of the mixtures occurs at an acetone mass fraction of ˜75%. The trend of concentration varying with mixture compositions could be well predicated by the model, which relates the concentration to the mixing enthalpy within the scope of HSP theory. The resultant dispersion is highly stabilized. Atomic force microscopic statistical analysis shows that up to ˜50% of the prepared nanosheets are less than 1 nm thick after 4 h sonication and 114g centrifugation. Analyses based on diverse characterizations indicate the graphene sheets to be largely free of basal plane defects and oxidation. The filtered films are also investigated in terms of their electrical and optical properties to show reasonable conductivity and transparency. The strategy of tailoring HSP, which can be easily extended to various solvent systems, and water/acetone mixtures here, extends the scope for large-scale production of graphene in low-boiling-point solutions.

  13. High therapeutic concentration of prazosin up-regulates angiogenic IL6 and CCL2 genes in hepatocellular carcinoma cells.

    PubMed

    Lin, Zu-Yau; Chuang, Wan-Long

    2012-12-01

    Alteration of the oxidative stress of hepatocellular carcinoma (HCC) cells can influence the expressions of genes favored angiogenesis. Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3. Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3. This study was to investigate the influence of therapeutic concentrations of prazosin (0.01 and 0.1μM) on cell proliferation and differential expressions of CCL2, CCL20, CXCL6, CXCL10, IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines. Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress (cell line A; HCC24/KMUH) and one with this effect (cell line B; HCC38/KMUH) were investigated by 0.01 and 0.1μM prazosin. The premixed WST-1 cell proliferation reagent was applied for proliferation assay. Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines. Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes. However, 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion, high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress. Clinical application of prazosin in patients with HCC should consider this possibility.

  14. Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.

    PubMed

    Hone, Arik J; Michael McIntosh, J; Rueda-Ruzafa, Lola; Passas, Juan; de Castro-Guerín, Cristina; Blázquez, Jesús; González-Enguita, Carmen; Albillos, Almudena

    2017-01-01

    Varenicline is a nicotinic acetylcholine receptor (nAChR) agonist used to treat nicotine addiction, but a live debate persists concerning its mechanism of action in reducing nicotine consumption. Although initially reported as α4β2 selective, varenicline was subsequently shown to activate other nAChR subtypes implicated in nicotine addiction including α3β4. However, it remains unclear whether activation of α3β4 nAChRs by therapeutically relevant concentrations of varenicline is sufficient to affect the behavior of cells that express this subtype. We used patch-clamp electrophysiology to assess the effects of varenicline on native α3β4* nAChRs (asterisk denotes the possible presence of other subunits) expressed in human adrenal chromaffin cells and compared its effects to those of nicotine. Varenicline and nicotine activated α3β4* nAChRs with EC50 values of 1.8 (1.2-2.7) μM and 19.4 (11.1-33.9) μM, respectively. Stimulation of adrenal chromaffin cells with 10 ms pulses of 300 μM acetylcholine (ACh) in current-clamp mode evoked sodium channel-dependent action potentials (APs). Under these conditions, perfusion of 50 or 100 nM varenicline showed very little effect on AP firing compared to control conditions (ACh stimulation alone), but at higher concentrations (250 nM) varenicline increased the number of APs fired up to 436 ± 150%. These results demonstrate that therapeutic concentrations of varenicline are unlikely to alter AP firing in chromaffin cells. In contrast, nicotine showed no effect on AP firing at any of the concentrations tested (50, 100, 250, and 500 nM). However, perfusion of 50 nM nicotine simultaneously with 100 nM varenicline increased AP firing by 290 ± 104% indicating that exposure to varenicline and nicotine concurrently may alter cellular behavior such as excitability and neurotransmitter release.

  15. DMR (deacetylation and mechanical refining) processing of corn stover achieves high monomeric sugar concentrations (230 g L-1) during enzymatic hydrolysis and high ethanol concentrations (>10% v/v) during fermentation without hydrolysate purification or concentration

    SciTech Connect

    Chen, Xiaowen; Kuhn, Erik; Jennings, Edward W.; Nelson, Robert; Tao, Ling; Zhang, Min; Tucker, Melvin P.

    2016-04-01

    Distilling and purifying ethanol and other products from second generation lignocellulosic biorefineries adds significant capital and operating costs to biofuel production. The energy usage associated with distillation negatively affects plant gate costs and causes environmental and life-cycle impacts, and the lower titers in fermentation caused by lower sugar concentrations from pretreatment and enzymatic hydrolysis increase energy and water usage and ethanol production costs. In addition, lower ethanol titers increase the volumes required for enzymatic hydrolysis and fermentation vessels increase capital expenditure (CAPEX). Therefore, increasing biofuel titers has been a research focus in renewable biofuel production for several decades. In this work, we achieved approximately 230 g L-1 of monomeric sugars after high solid enzymatic hydrolysis using deacetylation and mechanical refining (DMR) processed corn stover substrates produced at the 100 kg per day scale. The high sugar concentrations and low chemical inhibitor concentrations achieved by the DMR process allowed fermentation to ethanol with titers as high as 86 g L-1, which translates into approximately 10.9% v/v ethanol. To our knowledge, this is the first time that titers greater than 10% v/v ethanol in fermentations derived from corn stover without any sugar concentration or purification steps have been reported. As a result, the potential cost savings from high sugar and ethanol titers achieved by the DMR process are also reported using TEA analysis.

  16. DMR (deacetylation and mechanical refining) processing of corn stover achieves high monomeric sugar concentrations (230 g L-1) during enzymatic hydrolysis and high ethanol concentrations (>10% v/v) during fermentation without hydrolysate purification or concentration

    DOE PAGES

    Chen, Xiaowen; Kuhn, Erik; Jennings, Edward W.; ...

    2016-04-01

    Distilling and purifying ethanol and other products from second generation lignocellulosic biorefineries adds significant capital and operating costs to biofuel production. The energy usage associated with distillation negatively affects plant gate costs and causes environmental and life-cycle impacts, and the lower titers in fermentation caused by lower sugar concentrations from pretreatment and enzymatic hydrolysis increase energy and water usage and ethanol production costs. In addition, lower ethanol titers increase the volumes required for enzymatic hydrolysis and fermentation vessels increase capital expenditure (CAPEX). Therefore, increasing biofuel titers has been a research focus in renewable biofuel production for several decades. In thismore » work, we achieved approximately 230 g L-1 of monomeric sugars after high solid enzymatic hydrolysis using deacetylation and mechanical refining (DMR) processed corn stover substrates produced at the 100 kg per day scale. The high sugar concentrations and low chemical inhibitor concentrations achieved by the DMR process allowed fermentation to ethanol with titers as high as 86 g L-1, which translates into approximately 10.9% v/v ethanol. To our knowledge, this is the first time that titers greater than 10% v/v ethanol in fermentations derived from corn stover without any sugar concentration or purification steps have been reported. As a result, the potential cost savings from high sugar and ethanol titers achieved by the DMR process are also reported using TEA analysis.« less

  17. Therapeutic concentrations of tacrolimus do not interfere with endothelial nitric oxide synthesis in rat thoracic aortas and coronary arteries.

    PubMed

    Can, Cenk; Erol, Ayşe; Cinar, Mehtap; Olukman, Murat; Ulker, Sibel; Evinç, Akgün

    2007-10-01

    This study aimed to investigate the potential effect of in vivo administration of immunosuppressive agent FK-506 (tacrolimus) on the endothelial function of rat thoracic aortas with respect to nitric oxide (NO) synthesis. In vitro effect of the drug on NO synthesis in cultured rat coronary microvascular endothelial cells (CMEC) was also studied.In vivo administration of tacrolimus (1 mg/kg/d, intramuscular) to rats for 14 days resulted in decreased relaxant responses to the higher concentrations (1 to 30 muM) of acetylcholine in the aortas; however, responses to calcium ionophore A23187, sodium nitroprusside, L-arginine, and L-NAME did not change significantly. No changes were observed in phenylephrine-induced contractions in endothelium-denuded or -intact preparations. Administration of the vehicle for 14 days did not affect these parameters. In order to evaluate the in vitro effect of tacrolimus on NO release, CMEC isolated from rat hearts were incubated with either tacrolimus (0.01, 0.1 microM) or the vehicle. Basal, calcium ionophore-stimulated, or interleukin-1 beta-induced NO synthesis was determined by measuring total nitrite in the media. Neither tacrolimus nor the vehicle changed nitrite accumulation. It has been concluded that therapeutic concentrations of tacrolimus do not alter NO production in rat thoracic aorta or cultured CMEC; however, it impairs relaxant responses of rat aorta induced by higher concentrations of acetylcholine, possibly through changes in the downstream of receptor activation or through an imbalance between endothelium-dependent relaxant and contracting factors within the endothelium in favor of the contracting factor(s).

  18. Buccal mucosal delivery of a potent peptide leads to therapeutically-relevant plasma concentrations for the treatment of autoimmune diseases.

    PubMed

    Jin, Liang; Boyd, Ben J; White, Paul J; Pennington, Michael W; Norton, Raymond S; Nicolazzo, Joseph A

    2015-02-10

    Stichodactyla helianthus neurotoxin (ShK) is an immunomodulatory peptide currently under development for the treatment of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis by parenteral administration. To overcome the low patient compliance of conventional self-injections, we have investigated the potential of the buccal mucosa as an alternative delivery route for ShK both in vitro and in vivo. After application of fluorescent 5-Fam-ShK to untreated porcine buccal mucosa, there was no detectable peptide in the receptor chamber using an in vitro Ussing chamber model. However, the addition of the surfactants sodium taurodeoxycholate hydrate or cetrimide, and formulation of ShK in a chitosan mucoadhesive gel, led to 0.05-0.13% and 1.1% of the applied dose, respectively, appearing in the receptor chamber over 5h. Moreover, confocal microscopic studies demonstrated significantly enhanced buccal mucosal retention of the peptide (measured by mucosal fluorescence associated with 5-Fam-ShK) when enhancement strategies were employed. Administration of 5-Fam-ShK to mice (10mg/kg in a mucoadhesive chitosan-based gel (3%, w/v) with or without cetrimide (5%, w/w)) resulted in average plasma concentrations of 2.6-16.2nM between 2 and 6h, which were substantially higher than the pM concentrations required for therapeutic activity. This study demonstrated that the buccal mucosa is a promising administration route for the systemic delivery of ShK for the treatment of autoimmune diseases.

  19. Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations

    PubMed Central

    Brantley, Scott J.; Oberlies, Nicholas H.; Kroll, David J.

    2010-01-01

    Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC50 of 8.2, 18, 74, and >100 μM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9*1 (6.7 versus 12 μM), rCYP2C9*2 (9.3 versus 19 μM), and rCYP2C9*3 (2.4 versus 9.3 μM). Using a matrix of five substrate (1–15 μM) and six inhibitor (1–80 μM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (Ki values of 4.8 and 10 μM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5–75 μM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction. PMID:19934397

  20. Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

    PubMed Central

    W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

    2013-01-01

    Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

  1. Supra-therapeutic plasma concentrations of haloperidol induce moderate inhibition of lipopolysaccharide-induced interleukin-8 release in human monocytes

    PubMed Central

    2016-01-01

    Background The clinical use of antipsychotics and mood-stabilizing drugs with proven efficacy is largely determined by the occurrence of treatment-emergent adverse events and routine clinical chemistry and haematology data, which together define the safety and tolerability profile of these psychopharmaceuticals. Whereas the effects of mood-stabilizing drugs on functional properties of blood cells have been poorly investigated, the effects of antipsychotics have received more attention. Such studies have yielded conflicting results. This study examined the effects of the mood-stabilizing drugs carbamazepine and valproic acid and of the antipsychotic drugs olanzapine, risperidone and haloperidol on the production of the pro-inflammatory chemokine interleukin-8 (IL-8), which is released from human monocytes when activated by Gram-negative lipopolysaccharide (LPS). Methods Peripheral human whole blood was diluted with Roswell Park Memorial Institute (RPMI) cell culture medium and stimulated with LPS. Accumulating IL-8 was quantified in the supernatant with an adapted enzyme-linked immunosorbent assay (ELISA) and the results correlated to the number of monocytes at venipuncture. Results At supra-therapeutic concentrations of 100 µM, haloperidol inhibited the LPS-induced release of IL-8 in peripheral human monocytes moderately, whereas olanzapine, risperidone, carbamazepine and valproic acid showed no such effect. Conclusions The results suggest that these mood-stabilizing drugs and antipsychotics are endowed with clinically favorable inertness rather than pro-inflammatory properties. PMID:27867948

  2. Determination of Voriconazole Serum Concentration by Bioassay, a Valid Method for Therapeutic Drug Monitoring for Clinical Laboratories

    PubMed Central

    Cendejas-Bueno, Emilio; Cuenca-Estrella, Manuel

    2013-01-01

    We describe here a simple, fast, and reliable bioassay method for therapeutic drug monitoring of voriconazole. Fifty-eight clinical and external quality control samples were evaluated with this microbiological assay, and results were compared with those obtained with a previously validated chromatographic method. A good correlation between both assays was observed. This particular microbiological method was demonstrated to be simple and offers enough precision and accuracy to perform voriconazole therapeutic drug monitoring in laboratories without specialized equipment. PMID:23650161

  3. Room-temperature ferromagnetism in Cr-doped Si achieved by controlling atomic structure, Cr concentration, and carrier densities: A first-principles study

    SciTech Connect

    Wei, Xin-Yuan; Yang, Zhong-Qin; Zhu, Yan; Li, Yun

    2015-04-28

    By using first-principles calculations, we investigated how to achieve a strong ferromagnetism in Cr-doped Si by controlling the atomic structure and Cr concentration as well as carrier densities. We found that the configuration in which the Cr atom occupies the tetrahedral interstitial site can exist stably and the Cr atom has a large magnetic moment. Using this doping configuration, room-temperature ferromagnetism can be achieved in both n-type and p-type Si by tuning Cr concentration and carrier densities. The results indicate that the carrier density plays a crucial role in realizing strong ferromagnetism in diluted magnetic semiconductors.

  4. Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

    PubMed

    Pandey, Soumya; Nakagawa, Mayumi; Rosenbaum, Eric R; Arnaoutakis, Konstantinos; Hutchins, Laura F; Makhoul, Issam; Milojkovic, Natasha; Cottler-Fox, Michele

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

  5. Therapeutic concentrations of mitotane (o,p'-DDD) inhibit thyrotroph cell viability and TSH expression and secretion in a mouse cell line model.

    PubMed

    Zatelli, Maria Chiara; Gentilin, Erica; Daffara, Fulvia; Tagliati, Federico; Reimondo, Giuseppe; Carandina, Gianni; Ambrosio, Maria Rosaria; Terzolo, Massimo; Degli Uberti, Ettore C

    2010-06-01

    Mitotane therapy is associated with many side effects, including thyroid function perturbations mimicking central hypothyroidism, possibly due to laboratory test interference or pituitary direct effects of mitotane. We investigated whether increasing concentrations of mitotane in the therapeutic range might interfere with thyroid hormone assays and evaluated the effects of mitotane on a mouse TSH-producing pituitary cell line. TSH, free T(4), and free T(3) levels do not significantly change in sera from hypo-, hyper-, or euthyroid patients after addition of mitotane at concentrations in the therapeutic window. In the mouse TalphaT1 cell line, mitotane inhibits both TSH expression and secretion, blocks TSH response to TRH, and reduces cell viability, inducing apoptosis at concentrations in the therapeutic window. TRH is not capable of rescuing TalphaT1 cells from the inhibitory effects of mitotane on TSH expression and secretion, which appear after short time treatment and persist over time. Our results demonstrate that mitotane does not interfere with thyroid hormone laboratory tests but directly reduces both secretory activity and cell viability on pituitary TSH-secreting mouse cells. These data represent a possible explanation of the biochemical picture consistent with central hypothyroidism in patients undergoing mitotane therapy and open new perspectives on the direct pituitary effects of this drug.

  6. Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro

    PubMed Central

    Ha, Shin-Woo; Sikorski, James A.; Weitzmann, M. Neale; Beck, George R.

    2014-01-01

    Silica-based nanomaterials are generally considered to be excellent candidates for therapeutic applications particularly related to skeletal metabolism however the current data surrounding the safety of silica based nanomaterials is conflicting. This may be due to differences in size, shape, incorporation of composite materials, surface properties, as well as the presence of contaminants following synthesis. In this study we performed extensive in vitro safety profiling of ~50 nm spherical silica nanoparticles with OH-terminated or Polyethylene Glycol decorated surface, with and without a magnetic core, and synthesized by the Stöber method. Nineteen different cell lines representing all major organ types were used to investigate an in vitro lethal concentration (LC) and results revealed little toxicity in any cell type analyzed. To calculate an in vitro therapeutic index we quantified the effective concentration at 50% response (EC50) for nanoparticle-stimulated mineral deposition activity using primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not substantially altered by surface or magnetic core. The calculated Inhibitory concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic cells. These results demonstrate the pharmacological potential of certain silica-based nanomaterial formulations for use in treating bone diseases based on a favorable in vitro therapeutic index. PMID:24333519

  7. Fat-soluble vitamin and micromineral concentrations in preruminant dairy calves fed to achieve different growth rates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calf nutrition programs often limit nutrient intake from milk replacer during the first few weeks of life to promote dry-feed intake and early weaning. Recent studies indicate that feeding increased amounts of milk replacer with higher protein concentration improves growth performance and feed effi...

  8. Ethanol in pre-surgical hand rubs: concentration and duration of application for achieving European Norm EN 12791.

    PubMed

    Suchomel, M; Rotter, M

    2011-03-01

    In Europe, ethanol is a common active agent in hand rub formulations and nowadays it is also recommended in guidelines for hand hygiene published by the Centers for Disease Control and Prevention and by the World Health Organization. However, data on the range of concentrations and durations of application providing a basis for passing the efficacy test of the European norm EN 12791 are still lacking. Therefore, the bactericidal efficacy of rubbing clean hands with pure ethanol in volume concentrations of 95%, 85% or 75% during 3 min was compared with that of the reference procedure of EN 12791 employing n-propanol 60% v/v for 3 min, immediately and 3h after disinfection. Ethanol 85% was also tested at a 5 min application. A Latin-square design was used with 20 randomly allotted volunteers. Whereas the mean immediate bacterial reductions caused by ethanol at concentrations of 75% (log RF 1.68) and 95% (log RF 2.70) were significantly less efficacious compared to that of the reference (log RF 3.27), at 85% they were not significantly less active with both applications, 3 and 5 min (log RFs 2.90 and 3.12, respectively). Three hours after antisepsis, the bacterial reduction on the gloved hand was only significantly less efficacious than that of the reference when 75% ethanol was used. It is concluded that ethanol-based hand rubs have a good chance of meeting the EN 12791 requirements if their ethanol concentration is >75% v/v but <95% v/v and if they are applied for at least 3 min.

  9. Patients’ empowerment, physicians’ perceptions, and achievement of therapeutic goals in patients with type 1 and type 2 diabetes mellitus in Mexico

    PubMed Central

    Lavalle-González, Fernando J; Chiquete, Erwin

    2016-01-01

    Background Physicians’ perception may not parallel objective measures of therapeutic targets in patients with diabetes. This is an issue rarely addressed in the medical literature. We aimed to analyze physicians’ perception and characteristics of adequate control of patients with diabetes. Patients and methods We studied information on physicians and their patients who participated in the third wave of the International Diabetes Management Practices Study registry in Mexico. This analysis was performed on 2,642 patients, 203 with type 1 diabetes mellitus (T1DM) and 2,439 with type 2 diabetes mellitus (T2DM), treated by 200 physicians. Results The patients perceived at target had lower hemoglobin A1c (HbA1c) and fasting blood glucose than those considered not at target. However, overestimation of the frequency of patients with HbA1c <7% was 41.5% in patients with T1DM and 31.7% in patients with T2DM (underestimation: 2.8% and 8.0%, respectively). The agreement between the physicians’ perception and the class of HbA1c was suboptimal (κ: 0.612). Diabetologists and endocrinologists tested HbA1c more frequently than primary care practitioners, internists, or cardiologists; however, no differences were observed in mean HbA1c, for both T1DM (8.4% vs 7.2%, P=0.42) and T2DM (8.03% vs 8.01%, P=0.87) patients. Nevertheless, insulin users perceived at target, who practiced self-monitoring and self-adjustment of insulin, had a lower mean HbA1c than patients without these characteristics (mean HbA1c in T1DM: 6.8% vs 9.6%, respectively; mean HbA1c in T2DM: 7.0% vs 10.1%, respectively). Conclusion Although there is a significant physicians’ overestimation about the optimal glycemic control, this global impression and characteristics of patients’ empowerment, such as self-monitoring and self-adjustment of insulin, are associated with the achievement of targets. PMID:27555751

  10. Achieving the Middle Ground in an Age of Concentrated Extremes: Mixed Middle-Income Neighborhoods and Emerging Adulthood

    PubMed Central

    SAMPSON, ROBERT J.; MARE, ROBERT D.; PERKINS, KRISTIN L.

    2015-01-01

    This article focuses on stability and change in “mixed middle-income” neighborhoods. We first analyze variation across nearly two decades for all neighborhoods in the United States and in the Chicago area, particularly. We then analyze a new longitudinal study of almost 700 Chicago adolescents over an 18-year span, including the extent to which they are exposed to different neighborhood income dynamics during the transition to young adulthood. The concentration of income extremes is persistent among neighborhoods, generally, but mixed middle-income neighborhoods are more fluid. Persistence also dominates among individuals, though Latino-Americans are much more likely than African Americans or whites to be exposed to mixed middle-income neighborhoods in the first place and to transition into them over time, even when adjusting for immigrant status, education, income, and residential mobility. The results here enhance our knowledge of the dynamics of income inequality at the neighborhood level, and the endurance of concentrated extremes suggests that policies seeking to promote mixed-income neighborhoods face greater odds than commonly thought. PMID:26722129

  11. Exceptionally omnidirectional broadband light harvesting scheme for multi-junction concentrator solar cells achieved via ZnO nanoneedles.

    PubMed

    Yeh, Li-Ko; Tian, Wei-Cheng; Lai, Kun-Yu; He, Jr-Hau

    2016-12-14

    GaInP/GaAs/Ge triple-junction concentrator solar cells with significant efficiency enhancement were demonstrated with antireflective ZnO nanoneedles. The novel nanostructure was attained with a Zn(NO3)2-based solution containing vitamin C. Under one sun AM 1.5G solar spectrum, conversion efficiency of the triple-junction device was improved by 23.7% via broadband improvement in short-circuit currents of 3 sub-cells after the coverage by the nanoneedles with a graded refractive index profile. The efficiency enhancement further went up to 45.8% at 100 suns. The performance boost through the nanoneedles also became increasingly pronounced in the conditions of high incident angles and the cloudy weather, e.g. 220.0% of efficiency enhancement was observed at the incident angle of 60°. These results were attributed to the exceptional broadband omnidirectionality of the antireflective nanoneedles.

  12. Exceptionally omnidirectional broadband light harvesting scheme for multi-junction concentrator solar cells achieved via ZnO nanoneedles

    PubMed Central

    Yeh, Li-Ko; Tian, Wei-Cheng; Lai, Kun-Yu; He, Jr-Hau

    2016-01-01

    GaInP/GaAs/Ge triple-junction concentrator solar cells with significant efficiency enhancement were demonstrated with antireflective ZnO nanoneedles. The novel nanostructure was attained with a Zn(NO3)2-based solution containing vitamin C. Under one sun AM 1.5G solar spectrum, conversion efficiency of the triple-junction device was improved by 23.7% via broadband improvement in short-circuit currents of 3 sub-cells after the coverage by the nanoneedles with a graded refractive index profile. The efficiency enhancement further went up to 45.8% at 100 suns. The performance boost through the nanoneedles also became increasingly pronounced in the conditions of high incident angles and the cloudy weather, e.g. 220.0% of efficiency enhancement was observed at the incident angle of 60°. These results were attributed to the exceptional broadband omnidirectionality of the antireflective nanoneedles. PMID:27966621

  13. Exceptionally omnidirectional broadband light harvesting scheme for multi-junction concentrator solar cells achieved via ZnO nanoneedles

    NASA Astrophysics Data System (ADS)

    Yeh, Li-Ko; Tian, Wei-Cheng; Lai, Kun-Yu; He-Hau, Jr.

    2016-12-01

    GaInP/GaAs/Ge triple-junction concentrator solar cells with significant efficiency enhancement were demonstrated with antireflective ZnO nanoneedles. The novel nanostructure was attained with a Zn(NO3)2-based solution containing vitamin C. Under one sun AM 1.5G solar spectrum, conversion efficiency of the triple-junction device was improved by 23.7% via broadband improvement in short-circuit currents of 3 sub-cells after the coverage by the nanoneedles with a graded refractive index profile. The efficiency enhancement further went up to 45.8% at 100 suns. The performance boost through the nanoneedles also became increasingly pronounced in the conditions of high incident angles and the cloudy weather, e.g. 220.0% of efficiency enhancement was observed at the incident angle of 60°. These results were attributed to the exceptional broadband omnidirectionality of the antireflective nanoneedles.

  14. The PFA-100R cannot detect blood group-dependent inhibition of platelet function by eptifibatide or abciximab at therapeutic plasma concentrations.

    PubMed

    Feuring, M; Ruf, A; Schultz, A; Wehling, M

    2010-01-01

    Previous investigations revealed that AB0 blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group 0 compared to subjects with blood group A, B or AB, which might in turn result in a reduced inhibition of platelet aggregation in individuals with blood group 0. The aim of the present in vitro investigation was to elucidate the impact of AB0 blood group-dependent vWF concentrations on eptifibatide and abciximab mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100(R) at baseline and at increasing concentrations of eptifibatide and abciximab. It was stratified for blood group 0 vs A. If measured with the collagen/ADP cartridge, blood group 0 was associated with a prolonged mean baseline closure time in comparison with blood group A (94.3 +/- 14.6 s vs. 74.6 +/- 9.9 s, p = 0.007) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no statistically significant differences in closure times (167.4 +/- 83.9 s vs. 140.1 +/- 99.0 s, p = 0.562) could be found in the presence of eptifibatide (0.1 microg/ml). Higher concentrations of abciximab (1 microg/ml) than those of eptifibatide were needed to increase the closure times in both cartridges of the PFA-100, but at this concentration of abciximab differences in closure times could not be detected most probably due to higher variability at these drug concentrations. The PFA-100(R) is not suitable for monitoring abciximab or eptifibatide within the therapeutic concentration range because the highest concentrations where the PFA-100(R) had measurable closure times of below 300 s is much too low to lead to the necessary platelet inhibition and, consequently, does not resemble the in vivo situation.

  15. A prospective study of cyclosporine concentration in relation to its therapeutic effect and toxicity after renal transplantation.

    PubMed Central

    Lindholm, A; Dahlqvist, R; Groth, G G; Sjöqvist, F

    1990-01-01

    1. Cyclosporine (CsA) concentrations in plasma and whole blood were monitored prospectively in 66 consecutive kidney transplant recipients for 6 months after transplantation or until graft loss. Immunosuppression was based on treatment with CsA and prednisolone in 27 patients and CsA, azathioprine and prednisolone in 39 patients. 2. Whole blood and plasma samples (separated at 37 degrees C) were collected 10-12 h after CsA dosage twice weekly over the first 3 months and thereafter once weekly. CsA concentrations were measured by high pressure liquid chromatography (h.p.l.c.) in plasma, by specific and non-specific monoclonal radioimmunoassays (r.i.a.) in whole blood, and by polyclonal r.i.a. and polyclonal fluorescence polarization immunoassay (f.p.i.a.) in whole blood and plasma. 3. There were no differences between the treatment schedules regarding graft or patient survival, occurrence of acute rejection, nephrotoxicity or infection. 4. CsA concentrations were significantly lower at the time of acute rejection than one week earlier based on all of the analytical methods used except f.p.i.a. 5. The lowest CsA concentration, recorded during the first month after transplantation, was significantly lower in patients with than in patients without experience of acute rejection episodes when the CsA concentrations were measured by polyclonal r.i.a. in whole blood and plasma and by specific and non-specific monoclonal r.i.a. in whole blood, but not by h.p.l.c. in plasma or polyclonal f.p.i.a. in whole blood or plasma. 6. The highest CsA concentration recorded during the second post-transplantation month, was higher in patients with acute nephrotoxicity than in those without nephrotoxicity when CsA was measured by specific monoclonal r.i.a. in whole blood (471 +/- 409 ng ml-1 vs 327 +/- 150 ng ml-1, P less than 0.05), but not by the other methods. 7. The mean plasma h.p.l.c. concentration of CsA measured by h.p.l.c. during the first month after transplantation was

  16. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

    PubMed Central

    Anand, P.; Bley, K.

    2011-01-01

    Summary Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies. PMID:21852280

  17. "I am a scientist": How setting conditions that enhance focused concentration positively relate to student motivation and achievement outcomes in inquiry-based science

    NASA Astrophysics Data System (ADS)

    Ellwood, Robin B.

    This research investigated how student social interactions within two approaches to an inquiry-based science curriculum could be related to student motivation and achievement outcomes. This qualitative case study consisted of two cases, Off-Campus and On-Campus, and used ethnographic techniques of participant observation. Research participants included eight eighth grade girls, aged thirteen to fourteen years old. Data sources included formal and informal participant interviews, participant journal reflections, curriculum artifacts including quizzes, worksheets, and student-generated research posters, digital video and audio recordings, photographs, and researcher field notes. Data were transcribed verbatim and coded, then collapsed into emergent themes using NVIVO 9. The results of this research illustrate how setting conditions that promote focused concentration and communicative interactions can be positively related to student motivation and achievement outcomes in inquiry-based science. Participants in the Off-Campus case experienced more frequent states of focused concentration and out performed their peers in the On-Campus case on forty-six percent of classroom assignments. Off-Campus participants also designed and implemented a more cognitively complex research project, provided more in-depth analyses of their research results, and expanded their perceptions of what it means to act like a scientist to a greater extent than participants in the On-Campus case. These results can be understood in relation to Flow Theory. Student interactions that promoted the criteria necessary for initiating flow, which included having clearly defined goals, receiving immediate feedback, and maintaining a balance between challenges and skills, fostered enhanced student motivation and achievement outcomes. This research also illustrates the positive gains in motivation and achievement outcomes that emerge from student experiences with extended time in isolated areas referred to

  18. Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

    PubMed

    Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

    2016-10-01

    A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.

  19. Therapeutic Drug Monitoring (TDM) in psychiatry (part I): why studies attempting to correlate drug concentration and antidepressant response don't work.

    PubMed

    Preskorn, Sheldon H

    2014-03-01

    In this column, the first in a series discussing why therapeutic drug monitoring (TDM) is a seriously underutilized tool in psychiatry, the author explains why standard antidepressant registration trials are not able to establish a correlation between antidepressant response and the plasma concentration of biogenic amine antidepressants, such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. The problem is that such studies have a poor signal-to- noise ratio. In such studies, approximately one third of participants receiving drug respond specifically because of the drug, one third of participants receiving drug respond not because of the drug but rather because of the "placebo" effect inherent in participating in such a study, and one third of participants on drug do not respond sufficiently to be counted as responders. In analyzing the results of such studies, the data from these last two groups make it impossible to identify whether there is any relationship between drug concentration and antidepressant response. The next column in this series will discuss how TDM can be used as a "personalized medicine" tool to evaluate patients who are at risk for less than optimum response either because they may have much more rapid or much slower clearance of a drug than is usual as well as to identify adherence problems.

  20. Achieving low effluent NO3-N and TN concentrations in low influent chemical oxygen demand (COD) to total Kjeldahl nitrogen (TKN) ratio without using external carbon source

    NASA Astrophysics Data System (ADS)

    Cao, Jiashun; Oleyiblo, Oloche James; Xue, Zhaoxia; Otache, Y. Martins; Feng, Qian

    2015-07-01

    Two mathematical models were used to optimize the performance of a full-scale biological nutrient removal (BNR) activated treatment plant, a plug-flow bioreactors operated in a 3-stage phoredox process configuration, anaerobic anoxic oxic (A2/O). The ASM2d implemented on the platform of WEST2011 software and the BioWin activated sludge/anaerobic digestion (AS/AD) models were used in this study with the aim of consistently achieving the designed effluent criteria at a low operational cost. Four ASM2d parameters (the reduction factor for denitrification , the maximum growth rate of heterotrophs (µH), the rate constant for stored polyphosphates in PAOs ( q pp), and the hydrolysis rate constant ( k h)) were adjusted. Whereas three BioWin parameters (aerobic decay rate ( b H), heterotrophic dissolved oxygen (DO) half saturation ( K OA), and Y P/acetic) were adjusted. Calibration of the two models was successful; both models have average relative deviations (ARD) less than 10% for all the output variables. Low effluent concentrations of nitrate nitrogen (N-NO3), total nitrogen (TN), and total phosphorus (TP) were achieved in a full-scale BNR treatment plant having low influent chemical oxygen demand (COD) to total Kjeldahl nitrogen (TKN) ratio (COD/TKN). The effluent total nitrogen and nitrate nitrogen concentrations were improved by 50% and energy consumption was reduced by approximately 25%, which was accomplished by converting the two-pass aerobic compartment of the plug-flow bioreactor to anoxic reactors and being operated in an alternating mode. Findings in this work are helpful in improving the operation of wastewater treatment plant while eliminating the cost of external carbon source and reducing energy consumption.

  1. Stereoselective metabolism of donepezil and steady-state plasma concentrations of S-donepezil based on CYP2D6 polymorphisms in the therapeutic responses of Han Chinese patients with Alzheimer's disease.

    PubMed

    Lu, Jin; Wan, Lili; Zhong, Yuan; Yu, Qi; Han, Yonglong; Chen, Pengguo; Wang, Beiyun; Li, Wei; Miao, Ya; Guo, Cheng

    2015-11-01

    The therapeutic response rates of patients to donepezil vary from 20% to 60%, one of the reasons is their genetic differences in donepezil-metabolizing enzymes, which directly influence liver metabolism. However, the mechanism of donepezil metabolism and that of its enantiomers is unknown. This study evaluated CYP2D6 polymorphisms to elucidate the stereoselective metabolism of donepezil and to confirm the association between the steady-state plasma concentrations of the pharmaco-effective S-donepezil and the therapeutic responses of Han Chinese patients with Alzheimer's disease. The in vitro study of the stereoselective metabolism demonstrated that CYP2D6 is the predominant P450 enzyme that metabolizes donepezil and that different CYP2D6 alleles differentially affect donepezil enantiomers metabolism. A total of 77 Han Chinese patients with Alzheimer's disease were recruited to confirm these results, by measuring their steady-state plasma concentrations of S-donepezil. The related CYP2D6 genes were genotyped. Plasma concentrations of S-donepezil (based on CYP2D6 polymorphisms) were significantly associated with therapeutic responses. This finding suggests that plasma concentrations of S-donepezil influence therapeutic outcomes following treatment with donepezil in Han Chinese patients with Alzheimer's disease. Therefore, determining a patient's steady-state plasma concentration of S-donepezil in combination with their CYP2D6 genotype might be useful for clinically monitoring the therapeutic efficacy of donepezil.

  2. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  3. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  4. Achieving high-pressure and high-temperature within a TEM: Crystallographic defects as hosts for concentrating and storing carbon deep within Earth

    NASA Astrophysics Data System (ADS)

    Wu, J.; Buseck, P. R.

    2013-12-01

    Transmission electron microscopy in combination with in-situ high-pressure and high-temperature measurements is uniquely able to provide high-resolution data about materials under conditions resembling those in Earth's interior. By using nanocontainers of graphitized carbon, it is possible to achieve pressures and temperatures up to 40 GPa and 1200 °C, respectively. A wide range of relatively simple minerals and mineral analogs have been examined using this approach. By studying alpha-PbO2-type titanium dioxide (TiO2) and perovskite-structured nickel-doped lanthanum chromate (LaCr0.5Ni0.5O3), we show the influence of crystallographic defects in concentrating and storing carbon within these analogs to minerals occurring deep inside Earth. Such in-situ observations are impossible by using existing conventional high-pressure techniques. Figure 1. Temporal compression sequence of an anatase nanocrystal with two visible fault planes inside a multi-walled graphitic cage. (a)-(g) The times indicated in each panel are from the start of irradiation. Pressure was generated by shrinkage of the cage resulting from displacement damage by electrons (30 A/cm2) at 770 C. The disappearance of anatase (101) planes and emergence of alpha-PbO2-type TiO2 (110) planes indicates a phase transition between (e) and (f) (see insets).

  5. Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide, Cross-Sectional 3B Study

    PubMed Central

    Zhou, Xianghai; Ji, Linong; Ran, Xingwu; Su, Benli; Ji, Qiuhe; Pan, Changyu; Weng, Jianping; Ma, Changsheng; Hao, Chuanming; Zhang, Danyi; Hu, Dayi

    2016-01-01

    Background There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients. Methods Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24–27.9kg/m2 and ≥28.0kg/m2. Central obesity was defined as a waist circumference ≥80cm in women and ≥85cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90mmHg and LDL-C<2.6mmol/L. Results Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals. Conclusions Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients. PMID:26726883

  6. Decreasing aqueous mercury concentrations to achieve safe levels in fish: examining the water-fish relationship in two point-source contaminated streams

    SciTech Connect

    Mathews, Teresa J; Southworth, George R; Peterson, Mark J; Roy, W Kelly; Ketelle, Richard H; Valentine, Charles S; Gregory, Scott M

    2013-01-01

    East Fork Poplar Creek (EFPC) and White Oak Creek (WOC) are two mercury-contaminated streams located on the Department of Energy s Oak Ridge Reservation in east Tennessee. East Fork Poplar Creek is the larger and more contaminated of the two, with average aqueous mercury (Hg) concentrations exceeding those in reference streams by several hundred-fold. Remedial actions over the past 20 years have decreased aqueous Hg concentrations in EFPC by 85 %. Fish fillet concentrations, however, have not responded to this decrease in aqueous Hg and remain above the U.S. Environmental Protection Agency s ambient water quality criterion (AWQC) of 0.3 mg/kg. The lack of correlation between aqueous and fish tissue Hg concentrations in this creek has led to questions regarding the usefulness of target aqueous Hg concentrations and strategies for future remediation efforts. White Oak Creek has a similar contamination history but aqueous Hg concentrations in WOC are an order of magnitude lower than in EFPC. Despite the lower aqueous Hg concentrations, fish fillet concentrations in WOC have also been above the AWQC, making the most recent aqueous Hg target of 200 ng/L in EFPC seem unlikely to result in an effective decrease in fillet Hg concentrations. Recent monitoring efforts in WOC, however, suggest an aqueous total Hg threshold above which Hg bioaccumulation in fish may not respond. This new information could be useful in guiding remedial actions in EFPC and in other point-source contaminated streams.

  7. Acyclovir achieves a lower concentration in African HIV-seronegative, herpes simplex virus 2-seropositive women than in non-African populations.

    PubMed

    Lu, Yanhui; Celum, Connie; Wald, Anna; Baeten, Jared M; Cowan, Frances; Delany-Moretlwe, Sinead; Reid, Stewart E; Hughes, James P; Wilcox, Ellen; Corey, Lawrence; Hendrix, Craig W

    2012-05-01

    Acyclovir pharmacokinetics was evaluated in 68 HIV-seronegative, herpes simplex virus 2 (HSV-2)-seropositive African women, who received a single oral 400-mg dose of acyclovir, with plasma acyclovir concentrations measured over 8 h. Geometric mean peak concentration and area under the concentration-time curve were 0.31 μg/ml and 1.59 h · μg/ml, respectively, 54% and 52% lower than values from non-Africans. Lower acyclovir concentrations may partly explain the reduced acyclovir suppression of HSV-2 genital ulcer recurrence in HPTN 039 African women participants.

  8. [Therapeutic drug monitoring of zonisamide].

    PubMed

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

    2010-01-01

    Zonisamide is a second generation antiepileptic drug available in France since 2005. It provides a mechanism of action similar to those of phenytoin or carbamazepine. It is indicated in association in the treatment of partial epilepsy with or without secondary generalization. Zonisamide is well absorbed with maximum concentration achieved in 2 to 5 h. It is partly metabolized by the CYP3A4. Its elimination half-life is very long, around 60 h. Studies in adults and children show low concentration-efficacy and concentration-toxicity correlations, but a therapeutic range has been determined between 10 and 40 mg/L. Zonisamide is sensitive to the inductive molecules of CYP which will increase its clearance and decrease its half-life. A specific monitoring of patient is recommended in renal impairment. For this molecule, the interest of TDM has been evaluated: possibly useful.

  9. "I Am a Scientist": How Setting Conditions That Enhance Focused Concentration Positively Relate to Student Motivation and Achievement Outcomes in Inquiry-Based Science

    ERIC Educational Resources Information Center

    Ellwood, Robin B.

    2013-01-01

    This research investigated how student social interactions within two approaches to an inquiry-based science curriculum could be related to student motivation and achievement outcomes. This qualitative case study consisted of two cases, Off-Campus and On-Campus, and used ethnographic techniques of participant observation. Research participants…

  10. Combination therapeutics in complex diseases.

    PubMed

    He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

    2016-12-01

    The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases.

  11. Supraphysiological serum relaxin concentration during pregnancy achieved by in-vitro fertilization is strongly correlated to the number of growing follicles in the treatment cycle.

    PubMed

    Kristiansson, P; Svärdsudd, K; von Schoultz, B; Wramsby, H

    1996-09-01

    In order to analyse the relationship between the ovarian response to stimulation in in-vitro fertilization (IVF) treatment cycles and relaxin concentrations during subsequent pregnancies, 31 healthy women pregnant after IVF treatment were studied prospectively. The maximum number of follicles observed from day -4 to day -2 in relation to ovum retrieval and the number of oocytes recovered were recorded. In addition, blood samples were drawn in the follicular phase, the luteal phase, early pregnancy and at gestational weeks 12, 16, 20, 27 and 35 to assess oestradiol, progesterone, human chorionic gonadotrophin and relaxin. The maximum numbers (mean +/- SEM) of follicles observed and oocytes recovered were 9.0 +/- 0.6 and 6.1 +/- 0.5 respectively. The supraphysiological mean relaxin values were strongly correlated to the maximum number of follicles observed (r = 0.72, P < 0.0001) and the number of oocytes recovered (r = 0.64, P < 0.0001), indicating that the source of increased relaxin production during IVF pregnancy might be the ovary. These results are supported by experimental data. In the present study, the occurrence of multiple pregnancy was not associated with higher relaxin concentrations, which is further support for the hypothesis that the ovary is the main source of serum relaxin.

  12. In vitro and in vivo characterization of a high-purity, solvent/detergent-treated factor VIII concentrate: evidence for its therapeutic efficacy in von Willebrand's disease.

    PubMed

    Mazurier, C; De Romeuf, C; Parquet-Gernez, A; Goudemand, M

    1989-07-01

    A factor VIII (FVIII) concentrate, virus-inactivated by the solvent/detergent procedure, was studied in vitro. In contrast with most high-purity, virus-inactivated FVIII concentrates, it contains not only high levels of von Willebrand factor (vWF) antigen and ristocetin cofactor activity but also high molecular weight forms of von Willebrand factor. Furthermore, it is able to promote platelet adhesion on collagen in a perfusion system. In vivo studies performed in patients with different types of von Willebrand's disease provided evidence that this concentrate corrects Duke's bleeding time and prevents or stops haemorrhages. Thus, the particular advantages of this FVIII/vWF preparation are safety, low content of contamination proteins, and efficacy in von Willebrand's disease.

  13. Effect of carbon source on acclimatization of nitrifying bacteria to achieve high-rate partial nitrification of wastewater with high ammonium concentration

    NASA Astrophysics Data System (ADS)

    Mousavi, Seyyed Alireza; Ibrahim, Shaliza; Aroua, Mohamed Kheireddine

    2014-08-01

    Experiments in two laboratory-scale sequential batch reactors were carried out to investigate the effect of heterotrophic bacteria on nitrifying bacteria using external carbon sources. Partial nitrification of ammonium-rich wastewater during short-term acclimatization enriched the activity of ammonia-oxidizing bacteria in both reactors. Heterotrophic bacteria exhibited a minor effect on nitrifying bacteria, and complete removal of ammonium occurred at a rate of 41 mg L-1 h-1 in both reactors. The main strategy of this research was to carry out partial nitrification using high-activity ammonia-oxidizing bacteria with a high concentration of free ammonia (70 mg L-1). The NO2 -/(NO3 - + NO2 -) ratio was greater than 0.9 in both reactors most of the time.

  14. Achieving extremely concentrated aqueous dispersions of graphene flakes and catalytically efficient graphene-metal nanoparticle hybrids with flavin mononucleotide as a high-performance stabilizer.

    PubMed

    Ayán-Varela, M; Paredes, J I; Guardia, L; Villar-Rodil, S; Munuera, J M; Díaz-González, M; Fernández-Sánchez, C; Martínez-Alonso, A; Tascón, J M D

    2015-05-20

    The stable dispersion of graphene flakes in an aqueous medium is highly desirable for the development of materials based on this two-dimensional carbon structure, but current production protocols that make use of a number of surfactants typically suffer from limitations regarding graphene concentration or the amount of surfactant required to colloidally stabilize the sheets. Here, we demonstrate that an innocuous and readily available derivative of vitamin B2, namely the sodium salt of flavin mononucleotide (FMNS), is a highly efficient dispersant in the preparation of aqueous dispersions of defect-free, few-layer graphene flakes. Most notably, graphene concentrations in water as high as ∼50 mg mL(-1) using low amounts of FMNS (FMNS/graphene mass ratios of about 0.04) could be attained, which facilitated the formation of free-standing graphene films displaying high electrical conductivity (∼52000 S m(-1)) without the need of carrying out thermal annealing or other types of post-treatment. The excellent performance of FMNS as a graphene dispersant could be attributed to the combined effect of strong adsorption on the sheets through the isoalloxazine moiety of the molecule and efficient colloidal stabilization provided by its negatively charged phosphate group. The FMNS-stabilized graphene sheets could be decorated with nanoparticles of several noble metals (Ag, Pd, and Pt), and the resulting hybrids exhibited a high catalytic activity in the reduction of nitroarenes and electroreduction of oxygen. Overall, the present results should expedite the processing and implementation of graphene in, e.g., conductive inks, composites, and hybrid materials with practical utility in a wide range of applications.

  15. Effect of 3.2 vs. 3.8% sodium citrate concentration on anti-Xa levels for patients on therapeutic low molecular weight heparin.

    PubMed

    Payne, S; MacKinnon, K; Keeney, M; Morrow, B; Kovacs, M J

    2003-10-01

    In this study, we compared the effect of sodium citrate, a sample collection variable, on the anti-Xa levels of patients (n = 28) on dalteparin, a low molecular weight heparin. The median anti-Xa level for 3.2% sodium citrate was 0.235 U/ml while the median level for 3.8% sodium citrate was 0.230 U/ml. We conclude that different sodium citrate concentrations give statistically equivalent anti-Xa levels for the same samples. This conclusion is in contrast to the findings of the effect of sodium citrate concentration on International Normalized Ratio (INR) and activated partial-thromboplastin time (aPTT). In accordance with previous recommendations, we advocate the exclusive use of 3.2% sodium citrate in an effort to standardize coagulation testing.

  16. Therapeutic drug monitoring for antidepressant drug treatment.

    PubMed

    Ostad Haji, Elnaz; Hiemke, Christoph; Pfuhlmann, Bruno

    2012-01-01

    The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

  17. Therapeutic Recreation

    ERIC Educational Resources Information Center

    Parks and Recreation, 1971

    1971-01-01

    Graphic profiles of (1) the professional membership of the National Therapeutic Recreation Society, (2) state-level employment opportunities in the field, and (3) educational opportunities at U.S. colleges and universities. (MB)

  18. MACROMOLECULAR THERAPEUTICS

    PubMed Central

    Yang, Jiyuan; Kopeček, Jindřich

    2014-01-01

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

  19. Macromolecular therapeutics.

    PubMed

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated.

  20. Therapeutic proteins.

    PubMed

    Dimitrov, Dimiter S

    2012-01-01

    Protein-based therapeutics are highly successful in clinic and currently enjoy unprecedented recognition of their potential. More than 100 genuine and similar number of modified therapeutic proteins are approved for clinical use in the European Union and the USA with 2010 sales of US$108 bln; monoclonal antibodies (mAbs) accounted for almost half (48%) of the sales. Based on their pharmacological activity, they can be divided into five groups: (a) replacing a protein that is deficient or abnormal; (b) augmenting an existing pathway; (c) providing a novel function or activity; (d) interfering with a molecule or organism; and (e) delivering other compounds or proteins, such as a radionuclide, cytotoxic drug, or effector proteins. Therapeutic proteins can also be grouped based on their molecular types that include antibody-based drugs, Fc fusion proteins, anticoagulants, blood factors, bone morphogenetic proteins, engineered protein scaffolds, enzymes, growth factors, hormones, interferons, interleukins, and thrombolytics. They can also be classified based on their molecular mechanism of activity as (a) binding non-covalently to target, e.g., mAbs; (b) affecting covalent bonds, e.g., enzymes; and (c) exerting activity without specific interactions, e.g., serum albumin. Most protein therapeutics currently on the market are recombinant and hundreds of them are in clinical trials for therapy of cancers, immune disorders, infections, and other diseases. New engineered proteins, including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs, and proteins with optimized pharmacokinetics, are currently under development. However, in the last several decades, there are no conceptually new methodological developments comparable, e.g., to genetic engineering leading to the development of recombinant therapeutic proteins. It appears that a paradigm change in methodologies and understanding of mechanisms is needed to overcome major

  1. Deriving the therapeutic concentrations for clozapine and haloperidol: the apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor varies with the affinity of the competing radioligand.

    PubMed

    Seeman, P; Van Tol, H H

    1995-10-15

    The apparent dissociation constant, Ki, for a neuroleptic at the dopamine D2 or D4 receptor was consistently higher when competed against [3H]nemonapride than against [3H]spiperone which was in turn higher than that against [3H]raclopride. This finding obtained for all four types of dopamine receptors studied, including the native dopamine D2 receptor in the anterior pituitary tissue, the human D2long receptor, the human D2short receptor and the human D4.4 receptor. Some neuroleptics revealed a difference of over 10-fold between the Ki using [3H]nemonapride and the Ki using [3H]raclopride. The KD values of the three 3H-ligands and the neuroleptic Ki values were lower when using a much lower concentration of tissue, indicating that depletion of ligand presumably accounted for the phenomenon. The Ki values of each neuroleptic were related to the the tissue/buffer partition coefficients of the three 3H-ligands. Extrapolating the neuroleptic Ki value down to a tissue/buffer partition coefficient of unity or zero led to a Ki value for competition versus a water-soluble ligand such as dopamine. Clozapine extrapolated to a Ki value of 1.3 nM. Direct measurement gave a Ki value of 1.6 nM for [3H]clozapine at the dopamine D4 receptor. When competing versus endogenous dopamine, this clozapine value of 1.6 nM would rise to 20 nM for the blockade of 75% of dopamine D4 receptors, matching the observed therapeutic concentration of 18 nM. These data also explain why clozapine occupies 48% of the D2 receptors in patients when measured with [11C]raclopride, but between 0% and 22% when measured with [18F]methylspiperone or [18F]fluoroethylspiperone.

  2. Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

    PubMed

    Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William

    2012-06-01

    The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

  3. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.

  4. Engineering human cells for in vivo secretion of antibody and non-antibody therapeutic proteins.

    PubMed

    Sánchez-Martín, David; Sanz, Laura; Álvarez-Vallina, Luis

    2011-12-01

    Purified proteins such as antibodies are widely used as therapeutic agents in clinical medicine. However, clinical-grade proteins for therapeutic use require sophisticated technologies and are extremely expensive to produce. In vivo secretion of therapeutic proteins by genetically engineered human cells may advantageously replace injection of highly purified proteins. The use of gene transfer methods circumvents problems related to large-scale production and purification and offers additional benefits by achieving sustained concentrations of therapeutic protein with a syngenic glycosylation pattern that make the protein potentially less immunogenic. The feasibility of the in vivo production of therapeutic proteins by diverse cells/tissues has now been demonstrated using different techniques, such as ex vivo genetically modified cells and in vivo gene transfer mediated by viral vectors.

  5. Therapeutic cancer vaccines

    PubMed Central

    Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

    2015-01-01

    The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

  6. Pharmacodynamic Modeling of Clarithromycin against Macrolide-Resistant [PCR-Positive mef(A) or erm(B)] Streptococcus pneumoniae Simulating Clinically Achievable Serum and Epithelial Lining Fluid Free-Drug Concentrations

    PubMed Central

    Noreddin, Ayman M.; Roberts, Danielle; Nichol, Kim; Wierzbowski, Aleksandra; Hoban, Daryl J.; Zhanel, George G.

    2002-01-01

    The association between macrolide resistance mechanisms and clinical outcomes remains understudied. The present study, using an in vitro pharmacodynamic model, assessed clarithromycin (CLR) activity against mef(A)-positive and erm(B)-negative Streptococcus pneumoniae isolates by simulating free-drug concentrations in serum and both total (protein-bound and free) and free drug in epithelial lining fluid (ELF). Five mef(A)-positive and erm(B)-negative strains, one mef(A)-negative and erm(B)-positive strain, and a control [mef(A)-negative and erm(B)-negative] strain of S. pneumoniae were tested. CLR was modeled using a one-compartment model, simulating a dosage of 500 mg, per os, twice a day (in serum, free-drug Cp maximum of 2 μg/ml, t1/2 of 6 h; in ELF, CELF(total) maximum of 35μg/ml, t1/2 of 6 h; CELF(free) maximum of 14 μg/ml, t1/2 of 6 h). Starting inocula were 106 CFU/ml in Mueller-Hinton broth with 2% lysed horse blood. With sampling at 0, 4, 8, 12, 20, and 24 h, the extent of bacterial killing was assessed. Achieving CLR T/MIC values of ≥90% (AUC0-24/MIC ratio, ≥61) resulted in bacterial eradication, while T>MIC values of 40 to 56% (AUC0-24/MIC ratios of ≥30.5 to 38) resulted in a 1.2 to 2.0 log10 CFU/ml decrease at 24 h compared to that for the initial inoculum. CLR T/MIC values of ≤8% (AUC0-24/MIC ratio, ≤17.3) resulted in a static effect or bacterial regrowth. The high drug concentrations in ELF that were obtained clinically with CLR may explain the lack of clinical failures with mef(A)-producing S. pneumoniae strains, with MICs up to 8 μg/ml. However, mef(A) isolates for which MICs are ≥16 μg/ml along with erm(B) may result in bacteriological failures. PMID:12435719

  7. Pharmacodynamic modeling of clarithromycin against macrolide-resistant [PCR-positive mef(A) or erm(B)] Streptococcus pneumoniae simulating clinically achievable serum and epithelial lining fluid free-drug concentrations.

    PubMed

    Noreddin, Ayman M; Roberts, Danielle; Nichol, Kim; Wierzbowski, Aleksandra; Hoban, Daryl J; Zhanel, George G

    2002-12-01

    The association between macrolide resistance mechanisms and clinical outcomes remains understudied. The present study, using an in vitro pharmacodynamic model, assessed clarithromycin (CLR) activity against mef(A)-positive and erm(B)-negative Streptococcus pneumoniae isolates by simulating free-drug concentrations in serum and both total (protein-bound and free) and free drug in epithelial lining fluid (ELF). Five mef(A)-positive and erm(B)-negative strains, one mef(A)-negative and erm(B)-positive strain, and a control [mef(A)-negative and erm(B)-negative] strain of S. pneumoniae were tested. CLR was modeled using a one-compartment model, simulating a dosage of 500 mg, per os, twice a day (in serum, free-drug C(p) maximum of 2 micro g/ml, t(1/2) of 6 h; in ELF, C(ELF(total)) maximum of 35 micro g/ml, t(1/2) of 6 h; C(ELF(free)) maximum of 14 micro g/ml, t(1/2) of 6 h). Starting inocula were 10(6) CFU/ml in Mueller-Hinton broth with 2% lysed horse blood. With sampling at 0, 4, 8, 12, 20, and 24 h, the extent of bacterial killing was assessed. Achieving CLR T/MIC values of > or =90% (AUC(0-24)/MIC ratio, > or =61) resulted in bacterial eradication, while T>MIC values of 40 to 56% (AUC(0-24)/MIC ratios of > or =30.5 to 38) resulted in a 1.2 to 2.0 log(10) CFU/ml decrease at 24 h compared to that for the initial inoculum. CLR T/MIC values of < or =8% (AUC(0-24)/MIC ratio, < or =17.3) resulted in a static effect or bacterial regrowth. The high drug concentrations in ELF that were obtained clinically with CLR may explain the lack of clinical failures with mef(A)-producing S. pneumoniae strains, with MICs up to 8 micro g/ml. However, mef(A) isolates for which MICs are > or =16 micro g/ml along with erm(B) may result in bacteriological failures.

  8. [Therapeutic drug monitoring of levetiracetam].

    PubMed

    Dailly, Eric; Bouquié, Régis; Bentué-Ferrer, Danièle

    2010-01-01

    Levetiracetam is an anticonvulsant drug used to treat partial seizures, myoclonic seizures of juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures. A review of the literature with an evidence-based medicine method highlighted parameters (age, renal failure, pregnancy, combination with other anticonvulsant drugs) which affect levetiracetam pharmacokinetics but no significant relationship between plasma concentration of levetiracetam and efficacy or toxicity. Concentrations usually observed in therapeutics is from 6 to 18 mg/L. However, the determination of an individual therapeutic concentration, associated with an effective and well tolerated therapy, could be recommended particularly before pregnancy. Consequently, therapeutic drug monitoring of levetiracetam which is not currently recommended could be possibly useful in specific clinical situations.

  9. [Therapeutic drug monitoring of oxcarbazepine].

    PubMed

    Bouquié, Régis; Dailly, Eric; Bentué-Ferrer, Danièle

    2010-01-01

    Oxcarbazepine is an analogue of carbamazepine, used for the treatment of partial seizure with or without secondary generalization. The two forms R and S of the mono-hydroxylated derivatives (MHD) are responsible for most of the anti-convulsant activity and it is the concentrations of MHD that are relevant in therapeutic drug monitoring (TDM). Analysis of currently literature provides no well-established relationship between plasma concentration of MHD and efficiency or toxicity. Although there is not a validated therapeutic range, the residual concentrations of usually observed therapeutic MHD are situated between 12 and 30 mg/L. In certain pathological or physiological circumstances, the pharmacokinetic variability of the oxcarbazepine can be considerable, but this strong unpredictability does not nevertheless justify the TDM of the MHD. Based on the available evidence, TDM of MHD is not routinely warranted but may be possibly useful in specific situations such as pregnancy or renal insufficiency.

  10. The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients

    PubMed Central

    Hassine, Anis; Laouani, Aicha; Amor, Sana Ben; Nouira, Manel; Ammou, Sofiène Ben

    2016-01-01

    Introduction The prescribed dose and carbamazepine plasma concentration to achieve the optimal therapeutic efficacy are highly variable from one patient to the other. Our study aimed to determine whether biological parameters may be used as plasma markers that can individually adjust the carbamazepine dose necessary to optimize therapeutic efficacy. Material and methods Ninety-four epileptic patients under carbamazepine monotherapy and who have never used combination therapy were recruited from the consecutive admissions at the Department of Neurology “CHU Sahloul” of Sousse Central Hospital in Tunisia from February 2010 to April 2011. The patients were monitored for epilepsy for three years on average. Carbamazepine and 10,11-epoxide-carbamazepine concentrations were analyzed through high-performance liquid chromatography. Simultaneously, therapeutic efficacy was assessed through the annual number of seizures in each patient. Results Our results showed the absence of any significant correlations between specific dose (mg/kg/day), carbamazepine plasma concentrations and therapeutic efficacy (r = 0.0025, p = 0.30; r = 0.1584, p = 0.38 respectively), whereas both plasma 10,11-epoxide-carbamazepine concentration and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with therapeutic efficacy (r = 0.34, p = 0.03; r = 0.45, p = 0.008 respectively). The optimum therapeutic response was observed among patients who simultaneously had a plasma concentration of 0.8 μg/ml of metabolite and 5.5 μg/ml of carbamazepine. Conclusions The results suggest that plasma levels of both carbamazepine and of 10,11-epoxide-carbamazepine must be set to achieve an optimum therapeutic response.

  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.

    PubMed

    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. Accolades or Achievement? Addressing the Unforeseen Consequences of Therapeutic Pedagogy

    ERIC Educational Resources Information Center

    McWilliam, Erica

    2015-01-01

    In June this year, Wellesley High School became a focus of attention worldwide, following a graduation speech made by a teacher at the school. Departing from the traditional rhetoric of such ceremonies, English teacher David McCullough told the assembled graduates that they were neither special nor exceptional, but may well believe they were…

  13. Ethics Audit of a Therapeutic Recreation Course

    ERIC Educational Resources Information Center

    Nisbett, Nancy; Hinton, Jennifer

    2008-01-01

    The purpose of this study was to enhance awareness of the presence of ethics education within the allied health discipline of therapeutic recreation. To achieve this end, a curriculum audit was conducted in a therapeutic recreation course to determine the existence of ethics education within the course. Included topics, methods of delivery, and…

  14. [Therapeutic drug monitoring of clozapine].

    PubMed

    Djerada, Zoubir; Daviet, Françoise; Llorca, Pierre-Michel; Eschalier, Alain; Saint-Marcoux, Franck; Bentué-Ferrer, Danièle; Libert, Fréderic

    2016-08-24

    Clozapine is a prototypical atypical antipsychotic used to treat severe schizophrenia and for which a therapeutic drug monitoring (TDM) is quite commonly proposed. Clozapine is rapidly absorbed (maximum concentration reached within 1 to 4hours), and is extensively metabolized in the liver by CYP1A2 to an active metabolite (and to a lesser extent, to inactive metabolites via other enzymes). Its half-life is 8 to 16h. A therapeutic range has been proposed for clozapine as some studies have reported both a relationship between low plasmatic concentrations and resistance to treatment (threshold level is likely between 250 and 400μg/L), and a relationship between high plasmatic concentrations and an increase in the occurrence of toxicity (alert level=1000μg/L). Given the data obtained in different studies, the TDM was evaluated for this molecule, to recommended.

  15. Graded Achievement, Tested Achievement, and Validity

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2015-01-01

    Twenty-eight studies of grades, over a century, were reviewed using the argument-based approach to validity suggested by Kane as a theoretical framework. The review draws conclusions about the meaning of graded achievement, its relation to tested achievement, and changes in the construct of graded achievement over time. "Graded…

  16. Flat high concentration devices

    SciTech Connect

    Minano, J.C.; Gonzalez, J.C.; Zanesco, I.

    1994-12-31

    During the last five years new concentrators achieving the theoretical maximum acceptance-angle-concentration product have appeared. In addition, some of these concentrators are very compact (concentrator depth/aperture diameter smaller than 1/3). The feasibility of these concentrators for photovoltaic applications is studied. It is concluded that these concentrators may be useful for high concentration cells (irradiance for maximum efficiency greater than 800 suns) if these cells have a small size (diameter smaller than 5 mm). The concentrators may provide for this case an acceptance angle of {approx} {+-}2.7 degrees with concentration factor around 1,000x and a concentrator depth 10 times the cell diameter. Instantaneous direct insolation and ambient temperature measurements of Madrid and a thermal model of the heat sink is used to calculate the annual electric energy output with which different concentration factors are compared. Concentration of 1,000x is close to the one giving the maximum annual electrical output.

  17. [Evidence-based therapeutic drug monitoring for saquinavir].

    PubMed

    Muret, Patrice; Solas, Caroline

    2011-01-01

    The human immunodeficiency virus (HIV) protease inhibitor saquinavir displays a large inter-individual variability in its pharmacokinetic parameters, related to a low absorption rate and an important hepatic metabolism. Based on literature, is the saquinavir therapeutic drug monitoring relevant? In naïve HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a saquinavir plasma trough concentration >100 ng/mL. Two studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of virologic response with a threshold value around 40 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 abdominal pains was more frequently associated with high concentrations of saquinavir, but without threshold value determination. Several studies, one of which was randomized, have reported the interest of saquinavir therapeutic drug monitoring to optimize the virologic response. Therefore, the level of evidence of the interest of saquinavir therapeutic drug monitoring is "recommended".

  18. [Therapeutic drug monitoring of olanzapine].

    PubMed

    Djerada, Zoubir; Brousse, Georges; Niel, Philippe; Llorca, Pierre-Michel; Eschalier, Alain; Bentue-Ferrer, Danièle; Libert, Fréderic

    2016-10-25

    Olanzapine, atypical antipsychotic, is used to treat schizophrenia and bipolar disorder. Its therapeutic drug monitoring (TDM) is quite commonly done. Olanzapine is well absorbed orally (bioavailability: 85 %), with peak plasma occurring between 4 and 6hours after oral administration. It is extensively metabolized by different hepatic enzymes (including CYP1A2 and CYP2D6 isoforms) to a large number of inactive metabolites, and its half-life is between 30 and 60hours. No specific therapeutic range, or threshold concentration could not be a consensus, but the higher intra- and interindividual variability, as well as the existence of studies suggesting a correlation between circulating concentrations of olanzapine and occurrence of therapeutic relapse or toxic phenomena appear to justify the STP for this molecule. Given these data, the interest of the STP was evaluated for this molecule to: recommended with therapeutic window of 20μg/L to 80μg/L.

  19. [Therapeutic drug monitoring of clobazam].

    PubMed

    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.

  20. Thin solar concentrator with high concentration ratio

    NASA Astrophysics Data System (ADS)

    Lin, Jhe-Syuan; Liang, Chao-Wen

    2013-09-01

    Solar concentrators are often used in conjunction with III-V multi-junction solar cells for cost reduction and efficiency improvement purposes. High flux concentration ratio, high optical efficiency and high manufacture tolerance are the key features required for a successful solar concentrator design. This paper describes a novel solar concentrator that combines the concepts, and thus the advantages, of both the refractive type ad reflective type. The proposed concentrator design adopts the Etendue-cascading concept that allows the light beams from all the concentric annular entrance pupils to be collected and transferred to the solar cell with minimal loss. This concept enables the system to perform near its Etendue-Limit and have a high concentration ratio simultaneously. Thereby reducing the costs of solar cells and therefor achieves a better the per watts cost. The concentrator demonstrated has a thing aspect ratio of 0.19 with a zero back focal distance. The numerical aperture at the solar cell immersed inside the dielectric concentrator is as high as 1.33 achieving a unprecedented high optical concentration ratio design.

  1. Development of new RNAi therapeutics.

    PubMed

    Liu, G; Wong-Staal, F; Li, Q-X

    2007-02-01

    RNAi-mediated gene inactivation has become a cornerstone of the present day gene function studies that are the foundation of mechanism and target based drug discovery and development, which could potentially shorten the otherwise long process of drug development. In particular, the coming of age of "RNAi drug" could provide new promising therapeutics bypassing traditional approaches. However, there are technological hurdles need to overcome and the biological limitations need to consider for achieving effective therapeutics. Major hurdles include the intrinsic poor pharmacokinetic property of siRNA and major biological restrictions include off-target effects, interferon response and the interference with endogenous miRNA. Recent innovations in nucleic acid chemistry, formulations and delivery methods have gradually rendered it possible to develop effective RNAi-based therapeutics. Careful design based on the newest RNAi/miRNA biology can also help to minimize the potential tissue toxicity. If successful with systemic application, RNAi drug will no doubt revolutionize the whole drug development process. This review attempts to describe the progress in this area, including applications in preclinical models and recent favorable experience in a number of human trials of local diseases, along with the discussion on the potential limitations of RNAi therapeutics.

  2. Designing phage therapeutics.

    PubMed

    Goodridge, Lawrence D

    2010-01-01

    Phage therapy is the application of phages to bodies, substances, or environments to effect the biocontrol of pathogenic or nuisance bacteria. To be effective, phages, minimally, must be capable of attaching to bacteria (adsorption), killing those bacteria (usually associated with phage infection), and otherwise surviving (resisting decay) until they achieve attachment and subsequent killing. While a strength of phage therapy is that phages that possess appropriate properties can be chosen from a large diversity of naturally occurring phages, a more rational approach to phage therapy also can include post-isolation manipulation of phages genetically, phenotypically, or in terms of combining different products into a single formulation. Genetic manipulation, especially in these modern times, can involve genetic engineering, though a more traditional approach involves the selection of spontaneously occurring phage mutants during serial transfer protocols. While genetic modification typically is done to give rise to phenotypic changes in phages, phage phenotype alone can also be modified in vitro, prior to phage application for therapeutic purposes, as for the sake of improving phage lethality (such as by linking phage virions to antibacterial chemicals such as chloramphenicol) or survival capabilities (e.g., via virion PEGylation). Finally, phages, both naturally occurring isolates or otherwise modified constructs, can be combined into cocktails which provide collectively enhanced capabilities such as expanded overall host range. Generally these strategies represent different routes towards improving phage therapy formulations and thereby efficacy through informed design.

  3. Leader as achiever.

    PubMed

    Dienemann, Jacqueline

    2002-01-01

    This article examines one outcome of leadership: productive achievement. Without achievement one is judged to not truly be a leader. Thus, the ideal leader must be a visionary, a critical thinker, an expert, a communicator, a mentor, and an achiever of organizational goals. This article explores the organizational context that supports achievement, measures of quality nursing care, fiscal accountability, leadership development, rewards and punishments, and the educational content and teaching strategies to prepare graduates to be achievers.

  4. Therapeutic angiogenesis in cardiovascular disease

    PubMed Central

    Al Sabti, Hilal

    2007-01-01

    Atherosclerotic disease of the arteries is a major cause of coronary artery disease, peripheral vascular disease and stroke. Some patients are however not candidate for the standard treatment of angioplasty or bypass surgery. Hence there is tremendous enthusiasm for the utilization of angiogenesis as a therapeutic modality for atherosclerotic arterial disease. This augmentation of physiological neo-vascularization in cardiovascular disease can be achieved through different pathways. In this article we are reviewing the Use of Gene therapy, Protein therapy and cellular therapy. PMID:18021404

  5. Comparing Science Achievement Constructs: Targeted and Achieved

    ERIC Educational Resources Information Center

    Ferrara, Steve; Duncan, Teresa

    2011-01-01

    This article illustrates how test specifications based solely on academic content standards, without attention to other cognitive skills and item response demands, can fall short of their targeted constructs. First, the authors inductively describe the science achievement construct represented by a statewide sixth-grade science proficiency test.…

  6. [Therapeutic drug monitoring of quinine].

    PubMed

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

    2011-01-01

    Quinine is an antimalarial agent whose main mechanism of action on Plasmodium is to inhibit the transformation of toxic haem to polymeric non-toxic haemozoin. After oral and intramuscular administration, quinine is well absorbed, with peak plasma concentration reached in 1 to 3 hours. The pharmacokinetic of quinine differs depending on the severity of the disease: the volume of distribution and the clearance decrease proportionally to the infection, while the half-life increases. Plasma concentrations are approximately 50% higher in patients in the acute phase than in convalescence. Quinine is metabolized primarily by CYP3A4, implying changing the dosage when combined with inhibitors or inducers of CYP. The efficacy of quinine has been proved for residual concentrations above 5 mg/L (15 μmol/L) throughout the duration of treatment. Some side effects are concentration-dependent and a concentration of 20 mg/L (60 μmol/L) is considered as the threshold for toxicity. The 2007 consensus conference of the French Language Infectious Diseases Society calls for daily monitoring of plasma concentrations during the first 3 days of treatment targeting a trough concentration between 10 and 12 mg/L (30-36 μmol/L). For this compound, the level of evidence of the interest of therapeutic drug monitoring has been evaluated and the latter is recommended.

  7. Which Achievement Gap?

    ERIC Educational Resources Information Center

    Anderson, Sharon; Medrich, Elliott; Fowler, Donna

    2007-01-01

    From the halls of Congress to the local elementary school, conversations on education reform have tossed around the term "achievement gap" as though people all know precisely what that means. As it's commonly used, "achievement gap" refers to the differences in scores on state or national achievement tests between various…

  8. [Therapeutic drug monitoring of clonazepam].

    PubMed

    Debruyne, Danièle; Pailliet-Loilier, Magalie; Lelong-Boulouard, Véronique; Coquerel, Antoine; Bentué-Ferrer, Danièle

    2010-01-01

    Clonazepam is a 1-4 benzodiazepine mainly used to treat epilepsy and epileptiform convulsion state. Rapidly absorbed after oral administration, it is widely distributed in the organism and is extensively converted in metabolites, poorly or not active, eliminated mainly in urine (70%) and feces. Elimination half-life is long, around 40 h. In adult and child, several studies showed a concentration-effect relation. Meanwhile, a large inter-individual variability in the dose-concentration relation was observed. A 15-50 microg/L range of clonazepam blood concentrations appears to be retained as an acceptable target to control a majority of epileptic seizures. The Therapeutic Drug Monitoring (TDM) of clonazepam can be considered as possibly useful in case of association with CYP450 inducers or inhibitors, suspicion of poor observance, or toxicity signs.

  9. Photovoltaic concentrators

    NASA Astrophysics Data System (ADS)

    Boes, E. C.

    1980-01-01

    A status report on photovoltaic (PV) concentrators technology is presented. The major topics covered are as follows: (1) current PV concentrator arrays; designs, performances, and costs; (2) current PV concentrator array components; cells and cell assemblies, optical concentrators, support structures, tracking, and drive; (3) design of PV concentrator arrays; and (4) array manufacturing technology.

  10. [Evidence-based therapeutic drug monitoring for nevirapine].

    PubMed

    Muret, Patrice; Piedoux, Sarah; Solas, Caroline; Quaranta, Sylvie

    2011-01-01

    Nevirapine, a HIV non nucleosidic reverse transcriptase inhibitor, displays an inter-individual variability in its pharmacokinetics parameters, related to its hepatic metabolism. Based on literature, is the nevirapine therapeutic drug monitoring relevant? In naïve and pre-treated HIV infected patients, the probability of achieving and maintaining an undetectable HIV viral load was significantly associated with a nevirapine plasma trough concentration (C(trough)) > 4 000 ng/mL. The probability of virologic failure was significantly associated with a C(trough) < 3 000 ng/mL. Concerning the exposure-toxicity relationship, the emergence of hepatotoxicity was more frequently associated with high C(trough), especially in case of HCV coinfection. Non-randomized studies have reported the interest of nevirapine therapeutic drug monitoring to optimize the virologic response and, to a lesser extent, to prevent hepatotoxicity. Therefore, the level of evidence of the interest of nevirapine therapeutic drug monitoring is "recommended".

  11. [Evidence-based therapeutic drug monitoring of atazanavir].

    PubMed

    Solas, Caroline; Muret, Patrice

    2011-01-01

    The HIV protease inhibitor atazanavir presents a wide inter-individual variability related to an intense hepatic metabolism. Dose-dependent elevations of bilirubin have been frequently reported with atazanavir. Relative to literature, the atazanavir therapeutic drug monitoring can it be proposed? In naïve HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a plasma trough concentration (C(min)) of atazanavir >200 ng/mL. Studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of the virologic response with a threshold value around 200 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 hyperbilirubinemia was more frequently associated with C(min) > 750-800 ng/mL. Non-randomized studies have reported the interest of atazanavir therapeutic drug monitoring to optimize the virologic response and prevent severe bilirubin elevations. Therefore, the level of evidence of the interest of atazanavir therapeutic drug monitoring is recommended.

  12. Trends in Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Smith, Ralph W.

    1995-01-01

    Discusses the implications of the rapid, dramatic changes taking place in therapeutic recreation for individuals with physical disabilities. The article notes the impact of changes in managed care, examines programming trends in therapeutic recreation (adventure/outdoor education, competitive sports, handcycling, health enhancement activities, and…

  13. Therapeutic Recreation Practicum Manual.

    ERIC Educational Resources Information Center

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  14. Chicanoizing the Therapeutic Community

    ERIC Educational Resources Information Center

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  15. Impact of Therapeutic Camping

    ERIC Educational Resources Information Center

    Shniderman, Craig M.

    1974-01-01

    There has been little interest in, and only slight illumination of, the impact of therapeutic camping for emotionally disturbed children. This study seeks to validate the belief that camping is therapeutic. Subjects were 52 boys, 5 to 11 1/2 years of age. Results support the hypothesis. (Author/HMV)

  16. Enzyme therapeutics for systemic detoxification.

    PubMed

    Liu, Yang; Li, Jie; Lu, Yunfeng

    2015-08-01

    Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed.

  17. [Therapeutic drug monitoring of valproate].

    PubMed

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

    2010-01-01

    Valproic acid is an anticonvulsant drug available in France since 1967. It is a broad spectrum molecule indicated in various forms of epilepsy of the adult and the child, but it is also prescribed in the treatment of different other pathologies of nervous system. The divalproate sodium is indicated in the treatment of bipolar disorders. The valproic acid is marketed under various pharmaceutical forms, with different corresponding tmax values. But, whatever the administered preparation, the circulating active molecule is the ion valproate. Elimination half-life is from 11 to 20 h. Metabolization of valproate is important and represents its main route of elimination. Valpromide is comparable to a prodrug which metabolizes in valproate. The inter and intraindividual variability of the plasma concentrations are important. Several studies show a concentration-effect relationship, but two interventional trials ended in the lack of interest of the Therapeutic Drug Monitoring (TDM), although it is of current practice. However, numerous drug interactions may modify the plasma concentrations of valproate. The therapeutic range is from 50 to 100 mg/L (346-693 micromol/L). The level of proof of the interest of the TDM for this molecule was estimated in: recommended.

  18. Engineered microRNA therapeutics.

    PubMed

    Gibson, N W

    2014-01-01

    Targeting of microRNAs that are overexpressed or replacement of microRNAs whose expression is lost are two distinct and novel approaches to treat disease(s) driven by microRNA dysregulation. This can be achieved by chemical modification of either a single stranded oligonucleotide called an antimiR or a double stranded nucleic acid molecule termed a microRNA mimic.With hundreds of microRNAs identified and knowledge of their role in disease becoming clearer there is the prospect, over the coming years, to harness engineered microRNA therapeutics to revolutionise the way diseases are treated.Both types of engineered microRNA therapeutics have advanced into clinical development with human proof of concept achieved with an anti-miR targeting miR-122 (one of the most abundant microRNAs in human hepatocytes that is utilised by the hepatitis C virus to enable its function and replication). Rather than targeting individual proteins or enzymes involved in human disease, an opportunity now exists to modulate multiple different proteins/enzymes which act in concert in the progression of disease.

  19. Therapeutic surfactant-stripped frozen micelles

    NASA Astrophysics Data System (ADS)

    Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.

    2016-05-01

    Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like `top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and `bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

  20. Therapeutic surfactant-stripped frozen micelles

    PubMed Central

    Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.

    2016-01-01

    Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like ‘top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and ‘bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2–3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated. PMID:27193558

  1. [Therapeutic drug monitoring of tiagabine].

    PubMed

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

    2010-01-01

    Tiagabine, a second-generation anticonvulsant drug, is marketed in France since 1997. It is also prescribed outside marketing authorization in the treatment of anxiety. They are few studies allowing arguing a relation exposure efficiency or toxicity, but intra and inter individual important variations in serum concentrations are described. Hepatic insufficiency requires a dose adaptation. In patients treated with therapeutic dose, serum levels are between 20 and 100 microg/L (50-250 nmol/L). For this molecule, the level of proof of the interest of TDM was estimated in: remaining to estimate.

  2. [Therapeutic drug monitoring of gabapentin].

    PubMed

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

    2010-01-01

    Gabapentin is a structural analogue of GABA used in the treatment of the partial epilepsies of adult and child of more than 12 years, in monotherapy or in association with other anticonvulsant drugs. In association, gabapentin presents the advantage of not interfering with the other anticonvulsant drugs. The interindividual pharmacokinetic variability and the saturable absorption are, with the adaptation in case of renal insufficiency, the only arguments in favor of TDM. During clinical studies, the plasma concentrations of gabapentin were generally included between 2 and 20 mg/L. For this molecule, the level of proof of the interest of therapeutic drug monitoring was estimated in: possibly useful.

  3. [Therapeutic drug monitoring of pregabaline].

    PubMed

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

    2010-01-01

    Pregabaline, a second generation antiepileptic, is marketed in France since 2005. It is also indicated in the treatment of painful neuropathy and in generalized anxious disorder. Its pharmacokinetic profile: low metabolism and no binding to plasma proteins, is not in favour of the necessity of a TDM. But other studies would be necessary to concluded more definitively. Pregabalin however, required a dosage adjustment in case of renal insufficiency. The values of the plasma concentrations found after various doses are in agreement in the different studies, without that we can define a therapeutic range. For this molecule, the level of proof of the interest of TDM was estimated in: remaining to estimate.

  4. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

    In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

  5. Biomimetic particles as therapeutics.

    PubMed

    Meyer, Randall A; Sunshine, Joel C; Green, Jordan J

    2015-09-01

    In recent years, there have been major advances in the development of novel nanoparticle- and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health.

  6. 'No delays achiever'.

    PubMed

    2007-05-01

    The latest version of the NHS Institute for Innovation and Improvement's 'no delays achiever', a web based tool created to help NHS organisations achieve the 18-week target for GP referrals to first treatment, is available at www.nodelaysachiever.nhs.uk.

  7. Vicarious Achievement Orientation.

    ERIC Educational Resources Information Center

    Leavitt, Harold J.; And Others

    This study tests hypotheses about achievement orientation, particularly vicarious achievement. Undergraduate students (N=437) completed multiple-choice questionnaires, indicating likely responses of one person to the success of another. The sex of succeeder and observer, closeness of relationship, and setting (medical school or graduate school of…

  8. Heritability of Creative Achievement

    ERIC Educational Resources Information Center

    Piffer, Davide; Hur, Yoon-Mi

    2014-01-01

    Although creative achievement is a subject of much attention to lay people, the origin of individual differences in creative accomplishments remain poorly understood. This study examined genetic and environmental influences on creative achievement in an adult sample of 338 twins (mean age = 26.3 years; SD = 6.6 years). Twins completed the Creative…

  9. Confronting the Achievement Gap

    ERIC Educational Resources Information Center

    Gardner, David

    2007-01-01

    This article talks about the large achievement gap between children of color and their white peers. The reasons for the achievement gap are varied. First, many urban minorities come from a background of poverty. One of the detrimental effects of growing up in poverty is receiving inadequate nourishment at a time when bodies and brains are rapidly…

  10. Achievement-Based Resourcing.

    ERIC Educational Resources Information Center

    Fletcher, Mike; And Others

    1992-01-01

    This collection of seven articles examines achievement-based resourcing (ABR), the concept that the funding of educational institutions should be linked to their success in promoting student achievement, with a focus on the application of ABR to postsecondary education in the United Kingdom. The articles include: (1) "Introduction" (Mick…

  11. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  12. PK and PK/PD of doxycycline in drinking water after therapeutic use in pigs.

    PubMed

    Prats, C; El Korchi, G; Giralt, M; Cristòfol, C; Peña, J; Zorrilla, I; Saborit, J; Pérez, B

    2005-12-01

    A commercial doxycycline formulation was administered in drinking water to 12 pigs at the recommended dose of 10 mg/kg daily for 5 days. The mean plasma concentration at steady-state was 1.37 +/- 1.21 microg/mL, which was reached at 68 +/- 27.2 h postadministration. Absorption and elimination half-life values were 7.20 +/- 2.42 and 7.01 +/- 2.10 h, respectively. Most plasma concentrations during dosing were higher than the minimum inhibitory concentrations (MICs) described for the main porcine bacterial pathogens of the respiratory tract (Pasteurella multocida, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica and Mycoplasma hyopneumoniae). It is concluded that when pigs were treated with doxycycline in drinking water at the recommended rate, therapeutically effective concentrations were achieved throughout the treatment period, supporting the clinical use of this tetracycline in the control of respiratory infections. However, inter-animal differences were marked.

  13. [Therapeutic drug monitoring of felbamate].

    PubMed

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

    2010-01-01

    Felbamate is a derivative of meprobamate used in second-line partial epilepsy and in the Lennox-Gastaut syndrome. Felbamate is well absorbed and has linear kinetics: C(max) and AUC increasing linearly with dose. The metabolism takes place in the liver. Metabolites represent 40 to 60% of excretion and are eliminated via the urine. The half-life is between 15 and 23 hours. Clearance is dependent on renal function. There is a concentration - efficacy and concentration - toxicity relationship. These arguments are in favour of a TDM but the therapeutic range is not clearly established. Potentially fatal side effects can be caused by felbamate (aplastic anemia, acute liver failure), which limits its use because they are dose-independant.

  14. Recent Patents on Emerging Therapeutics for the Treatment of Glaucoma, Age Related Macular Degeneration and Uveitis

    PubMed Central

    Vadlapudi, Aswani Dutt; Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K.

    2014-01-01

    Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis. PMID:25414810

  15. Achievability for telerobotic systems

    NASA Astrophysics Data System (ADS)

    Kress, Reid L.; Draper, John V.; Hamel, William R.

    2001-02-01

    Methods are needed to improve the capabilities of autonomous robots to perform tasks that are difficult for contemporary robots, and to identify those tasks that robots cannot perform. Additionally, in the realm of remote handling, methods are needed to assess which tasks and/or subtasks are candidates for automation. We are developing a new approach to understanding the capability of autonomous robotic systems. This approach uses formalized methods for determining the achievability of tasks for robots, that is, the likelihood that an autonomous robot or telerobot can successfully complete a particular task. Any autonomous system may be represented in achievability space by the volume describing that system's capabilities within the 3-axis space delineated by perception, cognition, and action. This volume may be thought of as a probability density with achievability decreasing as the distance from the centroid of the volume increases. Similarly, any task may be represented within achievability space. However, as tasks have more finite requirements for perception, cognition, and action, each may be represented as a point (or, more accurately, as a small sphere) within achievability space. Analysis of achievability can serve to identify, a priori, the survivability of robotic systems and the likelihood of mission success; it can be used to plan a mission or portions of a mission; it can be used to modify a mission plan to accommodate unpredicted occurrences; it can also serve to identify needs for modifications to robotic systems or tasks to improve achievability. .

  16. Culture and Achievement Motivation

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    1974-01-01

    A framework is suggested for the cross-cultural study of motivation that stresses the importance of contextual conditions in eliciting achievement motivation and emphasizes cultural relativity in the definition of the concept. (EH)

  17. Achieving Salary Equity

    ERIC Educational Resources Information Center

    Nevill, Dorothy D.

    1975-01-01

    Three techniques are outlined for use by higher education institutions to achieve salary equity: salary prediction (using various statistical procedures), counterparting (comparing salaries of persons of similar rank), and grievance procedures. (JT)

  18. High concentration biotherapeutic formulation and ultrafiltration: Part 1 pressure limits.

    PubMed

    Lutz, Herb; Arias, Joshua; Zou, Yu

    2017-01-01

    High therapeutic dosage requirements and the desire for ease of administration drive the trend to subcutaneous administration using delivery systems such as subcutaneous pumps and prefilled syringes. Because of dosage volume limits, prefilled syringe administration requires higher concentration liquid formulations, limited to about 30 cP or roughly 100-300 g L(-1) for mAb's. Ultrafiltration (UF) processes are routinely used to formulate biological therapeutics. This article considers pressure constraints on the UF process that may limit its ability to achieve high final product concentrations. A system hardware analysis shows that the ultrafiltration cassette pressure drop is the major factor limiting UF systems. Additional system design recommendations are also provided. The design and performance of a new cassette with a lower feed channel flow resistance is described along with 3D modeling of feed channel pressure drop. The implications of variations in cassette flow channel resistance for scaling up and setting specifications are considered. A recommendation for a maximum pressure specification is provided. A review of viscosity data and theory shows that molecular engineering, temperature, and the use of viscosity modifying excipients including pH adjustment can be used to achieve higher concentrations. The combined use of a low pressure drop cassette with excipients further increased final concentrations by 35%. Guidance is provided on system operation to control hydraulics during final concentration. These recommendations should allow one to design and operate systems to routinely achieve the 30 cP target final viscosity capable of delivery using a pre-filled syringe. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:113-124, 2017.

  19. Joined concentric tubes

    DOEpatents

    DeJonghe, Lutgard; Jacobson, Craig; Tucker, Michael; Visco, Steven

    2013-01-01

    Tubular objects having two or more concentric layers that have different properties are joined to one another during their manufacture primarily by compressive and friction forces generated by shrinkage during sintering and possibly mechanical interlocking. It is not necessary for the concentric tubes to display adhesive-, chemical- or sinter-bonding to each other in order to achieve a strong bond. This facilitates joining of dissimilar materials, such as ceramics and metals.

  20. [Effect of therapeutic hyperventilation on blood lactate concentration].

    PubMed

    Brandt, L; Filos, K; Link, J

    1983-10-01

    The increase of blood lactate is a well known side effect of active and passive hyperventilation. In 22 patients who underwent controlled respiration after head injury or elective neurosurgical operations, we measured lactate, pyruvate, pH, and bicarbonate in central venous blood and investigated their interference by hypocapnia. The level of ventilation was between pCO2 equal 25 mmHg and pCO2 equal 45 mmHg, measured in the central venous blood. With decreasing pCO2, pH showed an increasing (from 7.40 +/- 0.015 to 7.50 +/- 0.068) and bicarbonate a decreasing tendency (from 25.46 +/- 1.32 mMol/l to 23.28 +/- 3.76 mMol/l). Lactate and pyruvate remained within the normal range down to a central venous pCO2 of 31 mmHg. But then with increasing hypocapnia both increased significantly (lactate 2.001 +/- 1.08 mMol/l, 0.098 +/- 0.068 mMol/l). At a pCO2-range of 25-27 mmHg (central venous) lactate continued increasing to 2.212 +/- 0.995 mMol/l whereas pyruvate dropped to 0.087 +/- 0.05 mMol/l. Therefore the possibility of hypocapnia-induced lacticemia seems to arise at a ventilation level less than 30 mmHg (pCO2 central venous). Production of excess-lactate may begin at a central venous pCO2 of 27 mmHg.

  1. Host modulation by therapeutic agents

    PubMed Central

    Elavarasu, Sugumari; Sekar, Santhosh; Murugan, Thamaraiselvan

    2012-01-01

    Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, nitrous oxide (NO) synthase inhibitors, recombinant human interleukin-11 (rhIL-11), omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA), mitogen-activated protein kinase (MAPK) inhibitors, nuclear factor-kappa B (NF-kb) inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α) are some of the therapeutic agents that have host modulation properties. PMID:23066265

  2. Therapeutic options for lip augmentation.

    PubMed

    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  3. Recent advances in cancer therapeutics.

    PubMed

    Chessum, Nicola; Jones, Keith; Pasqua, Elisa; Tucker, Michael

    2015-01-01

    In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry.

  4. Relationships between pharmacokinetic parameters of carbamazepine and therapeutic response in patients with bipolar disease.

    PubMed

    Chbili, Chahra; Bannour, Souhail; Khlifi, Saida; Ben Hadj Ali, Bechir; Saguem, Saad

    2014-01-01

    This study aimed to assess the relationship between plasma levels of carbamazepine and its active metabolite 10,11-epoxide-carbamazepine, and the therapeutic response in patients with bipolar disease. Thirteen patients were kept on a fixed individual dose of carbamazepine for 19 weeks under psychiatric care. Steady-state plasma concentrations of carbamazepine and its metabolite 10,11-epoxide-carbamazepine were measured at weeks 4, 12, and 20 by HPLC essay. Simultaneously, the psychopathologic state was assessed using the Brief Psychiatric rating scale (BPRS). Upon correlational analysis, mean BPRS scores did not correlate with the plasma levels of carbamazepine, whereas both mean plasma levels of 10, 11-epoxide-carbamazepine concentrations and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with mean values of BPRS scores (r = 0.80, p =10(-4), r= -0.89, p =10(-3) respectively). Optimum therapeutic response was observed among patients who had a plasma metabolite level of 1.4 μg/mL and a plasma carbamazepine concentrations of 7 μg/mL simultaneously. These results suggest that both plasma carbamazepine and 10,11-epoxide-carbamazepine levels must be fixed to achieve optimum therapeutic response. In order to reach these conditions, inhibitor drugs (such as valproic acid) or inductor drugs (such as phenobarbital) of epoxyde-hydrolase might be coadministered with the carbamazepine in order to adapt the plasma level of 10,11-epoxide-carbamazepine.

  5. Pluristem Therapeutics, Inc.

    PubMed

    Prather, William

    2008-01-01

    Pluristem Therapeutics, Inc., based in Haifa, Israel, is a regenerative, biotherapeutics Company dedicated to the commercialization of nonpersonalized (allogeneic) cell therapy products. The Company is expanding noncontroversial placental-derived mesenchymal stem cells via a proprietary 3D process, named PluriX, into therapeutics for a variety of degenerative, malignant and autoimmune disorders. Pluristem will be conducting Phase I trials in the USA with its first product, PLX-I, which addresses the global shortfall of matched tissue for bone marrow transplantation by improving the engraftment of hematopoietic stem cells contained in umbilical cord blood.

  6. Therapeutics for cognitive aging.

    PubMed

    Shineman, Diana W; Salthouse, Timothy A; Launer, Lenore J; Hof, Patrick R; Bartzokis, George; Kleiman, Robin; Luine, Victoria; Buccafusco, Jerry J; Small, Gary W; Aisen, Paul S; Lowe, David A; Fillit, Howard M

    2010-04-01

    This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people-approximately 200 in all-the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.

  7. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  8. Therapeutic Antioxidant Medical Gas

    PubMed Central

    Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

    2009-01-01

    Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

  9. Cytochrome P450 and therapeutic drug monitoring with respect to clozapine.

    PubMed

    Buur-Rasmussen, B; Brøsen, K

    1999-12-01

    Clozapine is an atypical antipsychotic drug that is mainly used for the treatment of refractory schizophrenia. Clozapine is eliminated by oxidation in the liver, predominantly by cytochrome P4501A2 (CYP1A2). Due to the influence of inhibitors, inducers and genetic factors on CYP1A2-activity, several studies have reported a very large interindividual variability in clozapine plasma concentrations at a fixed dose. A number of methods have been published for the measurement of clozapine and metabolites in plasma. Plasma concentrations are most frequently measured by high-performance liquid chromatography. Most methods measure clozapine and the main metabolite, norclozapine, whereas two methods measure clozapine and two metabolites. Several studies suggest that a minimum effective clozapine plasma concentration of >350 microg/l must be achieved in order to ensure acceptable clinical response, whereas the upper limit of the therapeutic interval not yet has been clearly defined. The occurrence of agranulocytosis, the most serious side-effect of clozapine treatment does not seem to be dose-related and it is not possible to predict which patients are at risk of developing agranulocytosis. The risk of central nervous system side-effects seems to increase with concentrations above 1300 microg/l. Monitoring of clozapine plasma concentrations is recommended during concomitant use of other drugs that are known to interact with the oxidation of clozapine, such as carbamazepine (inducer) or fluvoxamine (inhibitor). Overall, it is concluded that therapeutic drug monitoring may be of value in the clinical management of clozapine.

  10. Therapeutic Angiogenesis in Critical Limb Ischemia

    PubMed Central

    Ouma, Geoffrey O.; Zafrir, Barak; Mohler, Emile R.; Flugelman, Moshe Y.

    2013-01-01

    Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis. PMID:23129733

  11. Concentrating collectors

    SciTech Connect

    Not Available

    1981-06-01

    Selected specifications from sixteen concentrating collector manufacturers are tabulated. Eleven are linear parabolic trough collectors, and the others include slats, cylindrical trough, linear Fresnel lens, parabolic cylindrical Fresnel lens, and two point focus parabolic dish collectors. Also included is a brief discussion of the operating temperatures and other design considerations for concentrating collectors. (LEW)

  12. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  13. Developing Therapeutic Listening

    ERIC Educational Resources Information Center

    Lee, Billy; Prior, Seamus

    2013-01-01

    We present an experience-near account of the development of therapeutic listening in first year counselling students. A phenomenological approach was employed to articulate the trainees' lived experiences of their learning. Six students who had just completed a one-year postgraduate certificate in counselling skills were interviewed and the…

  14. Measuring Therapeutic Effectiveness.

    ERIC Educational Resources Information Center

    Callister, Sheldon L.

    In the recent past, there has been a great deal of effort directed toward developing techniques for documenting therapeutic outcome. Funding sources and the general public seem to be demanding more meaningful data which indicate, in a clear manner, whether or not the services they are paying for are of value. Mental health centers, like other…

  15. Antibody Therapeutics in Oncology

    PubMed Central

    Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

    2016-01-01

    One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment. PMID:27081677

  16. SALT and Spelling Achievement.

    ERIC Educational Resources Information Center

    Nelson, Joan

    A study investigated the effects of suggestopedic accelerative learning and teaching (SALT) on the spelling achievement, attitudes toward school, and memory skills of fourth-grade students. Subjects were 20 male and 28 female students from two self-contained classrooms at Kennedy Elementary School in Rexburg, Idaho. The control classroom and the…

  17. Iowa Women of Achievement.

    ERIC Educational Resources Information Center

    Ohrn, Deborah Gore, Ed.

    1993-01-01

    This issue of the Goldfinch highlights some of Iowa's 20th century women of achievement. These women have devoted their lives to working for human rights, education, equality, and individual rights. They come from the worlds of politics, art, music, education, sports, business, entertainment, and social work. They represent Native Americans,…

  18. Schools Achieving Gender Equity.

    ERIC Educational Resources Information Center

    Revis, Emma

    This guide is designed to assist teachers presenting the Schools Achieving Gender Equity (SAGE) curriculum for vocational education students, which was developed to align gender equity concepts with the Kentucky Education Reform Act (KERA). Included in the guide are lesson plans for classes on the following topics: legal issues of gender equity,…

  19. Achieving Peace through Education.

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    While it is generally agreed that peace is desirable, there are barriers to achieving a peaceful world. These barriers are classified into three major areas: (1) an erroneous view of human nature; (2) injustice; and (3) fear of world unity. In a discussion of these barriers, it is noted that although the consciousness and conscience of the world…

  20. Explorations in achievement motivation

    NASA Technical Reports Server (NTRS)

    Helmreich, Robert L.

    1982-01-01

    Recent research on the nature of achievement motivation is reviewed. A three-factor model of intrinsic motives is presented and related to various criteria of performance, job satisfaction and leisure activities. The relationships between intrinsic and extrinsic motives are discussed. Needed areas for future research are described.

  1. Increasing Male Academic Achievement

    ERIC Educational Resources Information Center

    Jackson, Barbara Talbert

    2008-01-01

    The No Child Left Behind legislation has brought greater attention to the academic performance of American youth. Its emphasis on student achievement requires a closer analysis of assessment data by school districts. To address the findings, educators must seek strategies to remedy failing results. In a mid-Atlantic district of the Unites States,…

  2. Appraising Reading Achievement.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    To determine quality sequence in pupil progress, evaluation approaches need to be used which guide the teacher to assist learners to attain optimally. Teachers must use a variety of procedures to appraise student achievement in reading, because no one approach is adequate. Appraisal approaches might include: (1) observation and subsequent…

  3. Cognitive Processes and Achievement.

    ERIC Educational Resources Information Center

    Hunt, Dennis; Randhawa, Bikkar S.

    For a group of 165 fourth- and fifth-grade students, four achievement test scores were correlated with success on nine tests designed to measure three cognitive functions: sustained attention, successive processing, and simultaneous processing. This experiment was designed in accordance with Luria's model of the three functional units of the…

  4. Graders' Mathematics Achievement

    ERIC Educational Resources Information Center

    Bond, John B.; Ellis, Arthur K.

    2013-01-01

    The purpose of this experimental study was to investigate the effects of metacognitive reflective assessment instruction on student achievement in mathematics. The study compared the performance of 141 students who practiced reflective assessment strategies with students who did not. A posttest-only control group design was employed, and results…

  5. Achieving All Our Ambitions

    ERIC Educational Resources Information Center

    Hartley, Tricia

    2009-01-01

    National learning and skills policy aims both to build economic prosperity and to achieve social justice. Participation in higher education (HE) has the potential to contribute substantially to both aims. That is why the Campaign for Learning has supported the ambition to increase the proportion of the working-age population with a Level 4…

  6. Improving Educational Achievement.

    ERIC Educational Resources Information Center

    New York University Education Quarterly, 1979

    1979-01-01

    This is a slightly abridged version of the report of the National Academy of Education panel, convened at the request of HEW Secretary Joseph Califano and Assistant Secretary for Education Mary F. Berry, to study recent declines in student achievement and methods of educational improvement. (SJL)

  7. The Achievement Club

    ERIC Educational Resources Information Center

    Rogers, Ibram

    2009-01-01

    When Gabrielle Carpenter became a guidance counselor in Northern Virginia nine years ago, she focused on the academic achievement gap and furiously tried to close it. At first, she was compelled by tremendous professional interest. However, after seeing her son lose his zeal for school, Carpenter joined forces with other parents to form an…

  8. Achievement in Problem Solving

    ERIC Educational Resources Information Center

    Friebele, David

    2010-01-01

    This Action Research Project is meant to investigate the effects of incorporating research-based instructional strategies into instruction and their subsequent effect on student achievement in the area of problem-solving. The two specific strategies utilized are the integration of manipulatives and increased social interaction on a regular basis.…

  9. Essays on Educational Achievement

    ERIC Educational Resources Information Center

    Ampaabeng, Samuel Kofi

    2013-01-01

    This dissertation examines the determinants of student outcomes--achievement, attainment, occupational choices and earnings--in three different contexts. The first two chapters focus on Ghana while the final chapter focuses on the US state of Massachusetts. In the first chapter, I exploit the incidence of famine and malnutrition that resulted to…

  10. Advancing Student Achievement

    ERIC Educational Resources Information Center

    Walberg, Herbert J.

    2010-01-01

    For the last half century, higher spending and many modern reforms have failed to raise the achievement of students in the United States to the levels of other economically advanced countries. A possible explanation, says Herbert Walberg, is that much current education theory is ill informed about scientific psychology, often drawing on fads and…

  11. NCLB: Achievement Robin Hood?

    ERIC Educational Resources Information Center

    Bracey, Gerald W.

    2008-01-01

    In his "Wall Street Journal" op-ed on the 25th of anniversary of "A Nation At Risk", former assistant secretary of education Chester E. Finn Jr. applauded the report for turning U.S. education away from equality and toward achievement. It was not surprising, then, that in mid-2008, Finn arranged a conference to examine the…

  12. Recent patents and emerging therapeutics for HIV infections: a focus on protease inhibitors.

    PubMed

    Patel, Mitesh; Mandava, Nanda K; Vadlapatla, Ramya Krishna; Mitra, Ashim K

    2013-07-01

    The inclusion of protease inhibitors (PIs) in highly active antiretroviral therapy has significantly improved clinical outcomes in HIV-1-infected patients. To date, PIs are considered to be the most important therapeutic agents for the treatment of HIV infections. Despite high anti-HIV-1 potency, poor oral bioavailability of PIs has been a major concern. For achieving therapeutic concentrations, large doses of PIs are administered, which results in unacceptable systemic toxicities. Such severe and long-term toxicities necessitate the development of safer and potentially promising PIs. Recently, considerable attention has been paid to the development of newer compounds capable of inhibiting wild-type and resistant HIV-1 protease. Some of these PIs have displayed potent HIV-1 protease inhibitory activity. In this review, we have made an attempt to provide an overview on clinically approved and newly developing PIs, and related recent patents in the development of novel PIs.

  13. [Therapeutic drug monitoring of topiramate].

    PubMed

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

    2010-01-01

    Topiramate, a second generation anticonvulsant drug, is marketed in France since 1997. It is also indicated in the prophylaxis of headache and is used, except legal notices, in the treatment of neuropathic pains and bipolar disorders. The efficiency and the risk of adverse reactions are dose dependent. However, the good correlation between the dosage and the plasmatic concentrations, and the relatively low interindividual variability, when we take into account the age and the association with an enzyme inducer, are not in favour of the interest of a dosage. Furthermore, there is a covering range between the effective and not effective concentrations, and levels susceptible or not to facilitate the appearance of an adverse event. There is no validated therapeutic range, but to the usual dosages the plasma concentrations are included between 5 and 20 mg/L (15-60 micromol/L), mostly in the low part of this interval. For this molecule, the level of proof of the interest of the TDM was estimated in: possibly useful.

  14. [Therapeutic drug monitoring of lamotrigine].

    PubMed

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

    2010-01-01

    Lamotrigine is a second generation anticonvulsant drug available in France since 1996. As other anticonvulsant drugs, lamotrigine is also used in type I bipolar disorders and except legal notices, in the treatment of neuropathic pains. It is mainly metabolized by the UDP-glucuronyltransferase in inactive metabolites. Its average half-life of elimination is of the order of 22 h, but it is reduced approximately at 14 h if it is associated with enzymatic inductors and increased at 70 h if lamotrigine is administered with sodium valproate. The pharmacokinetic parameters are modified at the young child's, but not in the old population. During the pregnancy, the plasmatic concentrations are lowered and re-increase strongly after the delivery, if dosages were adapted. The renal insufficiency does not require adaptation of dosage, on the other hand in case of severe hepatic insufficiency a decrease of the dose is to be considered. The correlation concentration-efficiency does not seem demonstrated, but there are not enough published studies and they included few patients. Furthermore, they were led with a methodology more pragmatic than rigorous. The correlation concentration-toxicity is better argued. The recommended therapeutic range is from 2.5 to 15 mg/L. For this molecule, the level of proof of the interest of the TDM was estimated in: possibly useful.

  15. Therapeutic targets in malignant glioblastoma microenvironment.

    PubMed

    Barcellos-Hoff, Mary Helen; Newcomb, Elizabeth W; Zagzag, David; Narayana, Ashwatha

    2009-07-01

    There is considerable evidence that the tissue microenvironment can suppress cancer and that microenvironment disruption is required for cancer growth and progression. Distortion of the microenvironment by tumor cells can promote growth, recruit nonmalignant cells that provide physiological resources, and facilitate invasion. Compared with the variable routes taken by cells to become cancers, the response of normal tissue to cancer is relatively consistent such that controlling cancer may be more readily achieved indirectly via the microenvironment. Here, we discuss 3 ideas about how the microenvironment, consisting of a vasculature, inflammatory cells, immune cells, growth factors, and extracellular matrix, might provide therapeutic targets in glioblastoma (GBM) in the context of radiotherapy (RT): (1) viable therapeutic targets exist in the GBM microenvironment, (2) RT alters the microenvironment of tissues and tumors; and (3) a potential benefit may be achieved by targeting the microenvironments induced by RT.

  16. [Therapeutic drug monitoring of vigabatrin].

    PubMed

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

    2010-01-01

    Vigabatrin is a second generation anticonvulsant drug available in France since 1995. It is an amino acid analogue of the GABA, marketed under the racemic form [R(-)/S(+)50/50], but only the S(+)-enantiomer is active. Neither the mechanism of action of vigabatrin, an irreversible enzymatic inhibition, nor its pharmacokinetic characteristics (no binding to plasma proteins, low metabolism, no interaction with CYP), are in favour of TDM. There is no validated therapeutic range, but to the recommended dosage of 1 to 3 g a day correspond plasma concentrations ranging from 0,8 to 36 mg/L (6 - 279 micromol/L). For this molecule, the level of proof of the interest of the TDM was estimated in: to be useless.

  17. Toward Intracellular Targeted Delivery of Cancer Therapeutics

    PubMed Central

    Pandya, Hetal; Debinski, Waldemar

    2013-01-01

    A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells. PMID:22671766

  18. Faculty achievement tracking tool.

    PubMed

    Pettus, Sarah; Reifschneider, Ellen; Burruss, Nancy

    2009-03-01

    Faculty development and scholarship is an expectation of nurse educators. Accrediting institutions, such as the Commission on Collegiate Nursing Education, the National League for Nursing Accrediting Commission, and the Higher Learning Commission, all have criteria regarding faculty achievement. A faculty achievement tracking tool (FATT) was developed to facilitate documentation of accreditation criteria attainment. Based on criteria from accrediting organizations, the roles that are addressed include scholarship, service, and practice. Definitions and benchmarks for the faculty as an aggregate are included. Undergoing reviews from different accrediting organizations, the FATT has been used once for accreditation of the undergraduate program and once for accreditation of the graduate program. The FATT is easy to use and has become an excellent adjunct for the preparation for accreditation reports. In addition, the FATT may be used for yearly evaluations, advancement, and merit.

  19. Project ACHIEVE final report

    SciTech Connect

    1997-06-13

    Project ACHIEVE was a math/science academic enhancement program aimed at first year high school Hispanic American students. Four high schools -- two in El Paso, Texas and two in Bakersfield, California -- participated in this Department of Energy-funded program during the spring and summer of 1996. Over 50 students, many of whom felt they were facing a nightmare future, were given the opportunity to work closely with personal computers and software, sophisticated calculators, and computer-based laboratories -- an experience which their regular academic curriculum did not provide. Math and science projects, exercises, and experiments were completed that emphasized independent and creative applications of scientific and mathematical theories to real world problems. The most important outcome was the exposure Project ACHIEVE provided to students concerning the college and technical-field career possibilities available to them.

  20. Concentrating Radioactivity

    ERIC Educational Resources Information Center

    Herrmann, Richard A.

    1974-01-01

    By concentrating radioactivity contained on luminous dials, a teacher can make a high reading source for classroom experiments on radiation. The preparation of the source and its uses are described. (DT)

  1. 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

    PubMed Central

    Shuster, Constantin; DeMarco, Mari L.; Rosenfeld, Gregory

    2016-01-01

    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. PMID:27957480

  2. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation†

    PubMed Central

    Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M.; Radovic-Moreno, Aleksandar F.; Farokhzad, Omid C.

    2013-01-01

    Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development

  3. [Level of evidence for therapeutic drug monitoring for docetaxel].

    PubMed

    Gerritsen-van Schieveen, Pauline; Royer, Bernard

    2010-01-01

    Pharmacokinetic properties of docetaxel, an anticancer drug, are though to be interesting for therapeutic drug monitoring: high inter- and intra-variability, relationship between exposure and efficacy and especially toxicity. Moreover, the 3-weekly administration, which is the more effective scheme, is also the more toxic. However, neutropenia can be modeled and be efficiently predicted without needing plasma drug concentrations. The level evidence of therapeutic drug monitoring is thus weak regarding the possibility to adapt dose regimen without drug concentrations.

  4. Sex Differences in Achievement.

    ERIC Educational Resources Information Center

    Cross, David

    1983-01-01

    Evaluates the commonly held idea that girls are better language learners than boys. Results indicate that boys are not weaker in any of the language skill areas tested. Recommends that future research concentrate on the sex and image of the teacher. (EKN)

  5. Personal Achievement Reading: Business.

    ERIC Educational Resources Information Center

    Swinton, Janet R.

    Exercises are provided in this set of four workbooks designed to aid students in business programs in building vocabulary and reading skills. Each workbook borrows from business terminology to provide explanations and exercises for a sequential series of instructional objectives. One workbook concentrates on developing the ability to determine…

  6. Multistage vector (MSV) therapeutics.

    PubMed

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers.

  7. Multistage vector (MSV) therapeutics

    PubMed Central

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-01-01

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  8. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

    The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

  9. A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient.

    PubMed

    Chang, Jeremy B; Quinnies, Kayla M; Realubit, Ronald; Karan, Charles; Rand, Jacob H; Tatonetti, Nicholas P

    2016-07-21

    A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7 ± 0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5 ± 1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay.

  10. Mild Hyperthermia Enhances Transport of Liposomal Gemcitabine and Improves in vivo Therapeutic Response

    PubMed Central

    Kirui, Dickson K; Celia, Christian; Molinaro, Roberto; Bansal, Shyam S.; Cosco, Donato; Fresta, Massimo; Shen, Haifa; Ferrari, Mauro

    2015-01-01

    Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod-mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery and anti-tumor efficacy in pancreatic cancer CAPAN-1 tumor model. MHT treatment led to a 3-fold increase in accumulation of 80-nm liposomes and enhanced spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment led to a 3-fold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg/kg Gem Lip led to a 2-fold increase in therapeutic efficacy and inhibition of CAPAN-1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect was confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg/kg Gem Lip achieved similar therapeutic efficacy as the use of 60 mg/kg free gemcitabine. In conclusion, we demonstrated improvements in vivo efficacy resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines. PMID:25721343

  11. Mild hyperthermia enhances transport of liposomal gemcitabine and improves in vivo therapeutic response.

    PubMed

    Kirui, Dickson K; Celia, Christian; Molinaro, Roberto; Bansal, Shyam S; Cosco, Donato; Fresta, Massimo; Shen, Haifa; Ferrari, Mauro

    2015-05-01

    Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod-mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery, and antitumor efficacy in pancreatic cancer CAPAN-1 tumor model. MHT treatment leads to a threefold increase in accumulation of 80-nm liposomes and enhances spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment lead to a threefold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg kg(-1) Gem Lip leads to a twofold increase in therapeutic efficacy and inhibition of CAPAN-1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect is confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg kg(-1) Gem Lip achieves similar therapeutic efficacy as the use of 60 mg kg(-1) free gemcitabine. In conclusion, improvements in vivo efficacy are demonstrated resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.

  12. [Therapeutic and toxic theophylline levels in asthma attacks--is there a need for additional theophylline?].

    PubMed

    Zeidman, A; Gardyn, J; Fradin, Z; Fink, G; Mittelman, M

    1997-07-01

    Although first-line therapy for bronchial asthma has changed over the past decade to anti-inflammatory medication such as inhaled corticosteroids and cromolyn with possible addition of beta-agonists, theophylline is still useful and therefore widely used. However, several studies have raised serious questions regarding its efficacy in acute asthmatic exacerbations. These studies, the narrow therapeutic range of the drug, the frequency of side effects and interactions with common drugs, and individual variation in clearance and metabolism, have prompted its reevaluation in the management of asthma. Therapeutic serum levels of theophylline are between 10 to 20 mcg/ml. Most adults achieve these concentrations with daily slow-release oral theophylline preparations, 200-400 mg (approximately 10 mg/Kg) twice a day. However, when such a patient presents to the emergency room (ER) in an asthmatic attack, immediate intravenous theophylline is often given, regardless of maintenance treatment. Since the rationale for this common therapeutic approach has been challenged, the current study was undertaken. Serum theophylline levels were measured in 23 consecutive asthmatics presenting to the ER in an acute attack. 15 (68%) had therapeutic levels (above 10 mcg/ml) and 2 had toxic levels (above 20 mcg/ml), prior to receiving the standard intravenous theophylline dose given for an attack. These data indicate that most patients with bronchial asthma on oral maintenance theophylline do not require additional intravenous theophylline when in an attack. It probably will not benefit them and may even induce serious theophylline toxicity.

  13. Antioxidant therapeutics for schizophrenia.

    PubMed

    Reddy, Ravinder; Reddy, Rajiv

    2011-10-01

    Pharmaceutical treatment for millions worldwide who have schizophrenia is limited to a handful of antipsychotics. Despite the proven efficacy of these drugs, the overall outcome for schizophrenia remains suboptimal. Thus, alternative treatment options are urgently needed. One possible approach may be antioxidant therapy. The extant evidence for the role of oxidative stress in the pathophysiology of schizophrenia offers a hypothesis-derived therapeutic approach in the form of antioxidants. Vitamins C and E, for example, are suitable for human clinical trials because they are readily available, inexpensive, and relatively safe. Research into the therapeutic use of antioxidants in schizophrenia can be grouped into two main clusters: for psychopathology and for side effects. Of these studies, some have been carefully conducted, but majority are open label. Use of antioxidants for treatment-related side effects has been more extensively investigated. The totality of the evidence to date suggests that specific antioxidants, such as N-acetyl cysteine, may offer tangible benefits for the clinical syndrome of schizophrenia, and vitamin E may offer salutary effects on glycemic effects of antipsychotics. However, a great deal of fundamental clinical research remains to be done before antioxidants can be routinely used therapeutically for schizophrenia and treatment-related complications.

  14. Polycyclic peptide therapeutics.

    PubMed

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases.

  15. Proteases as therapeutics

    PubMed Central

    Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

    2015-01-01

    Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

  16. Therapeutic antibody engineering

    PubMed Central

    Parren, Paul W.H.I.; Lugovskoy, Alexey A.

    2013-01-01

    It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.

  17. Data Concentrator

    NASA Technical Reports Server (NTRS)

    Willett, Mike

    2015-01-01

    Orbital Research, Inc., developed, built, and tested three high-temperature components for use in the design of a data concentrator module in distributed turbine engine control. The concentrator receives analog and digital signals related to turbine engine control and communicates with a full authority digital engine control (FADEC) or high-level command processor. This data concentrator follows the Distributed Engine Controls Working Group (DECWG) roadmap for turbine engine distributed controls communication development that operates at temperatures at least up to 225 C. In Phase I, Orbital Research developed detailed specifications for each component needed for the system and defined the total system specifications. This entailed a combination of system design, compiling existing component specifications, laboratory testing, and simulation. The results showed the feasibility of the data concentrator. Phase II of this project focused on three key objectives. The first objective was to update the data concentrator design modifications from DECWG and prime contractors. Secondly, the project defined requirements for the three new high-temperature, application-specific integrated circuits (ASICs): one-time programmable (OTP), transient voltage suppression (TVS), and 3.3V. Finally, the project validated each design by testing over temperature and under load.

  18. Therapeutic Drug Monitoring By Reverse Iontophoresis

    PubMed Central

    Nair, Anroop B; Goel, Ankit; Prakash, Shashi; Kumar, Ashok

    2011-01-01

    Therapeutic molecules possessing distinct pharmacokinetic variation, narrow therapeutic index and concentration dependent therapeutic/adverse effects demand constant monitoring. The current methods for blood sampling are invasive and possess low patient compliance. Human skin, selective and effective membrane to chemical permeation, offers an alternative route for the extraction of endogenous molecules in the body. Significant attention has been received in the application of reverse iontophoresis in extracting drugs/biomaterials from the subdermal region. This technique involves transiting of a low electric current across the skin usually with couple of skin electrodes to extract charged as well as neutral molecules. Electromigration and electroosmosis are the two basic mechanisms involved in transport of molecules. Several in vitro and in vivo experiments demonstrated the potential of reverse iontophoresis as a noninvasive tool in clinical chemistry and therapeutic drug monitoring. This technology is currently being used in device such as Glucowatch Biogrpaher which allows blood glucose detection across skin layers. Advances in technology and rapid progress in research has widely improved the opportunity of this system, and the recent trend indicates that several products are likely to be developed very soon. This review provides an overview about the recent developments in reverse iontophoresis for therapeutic drug monitoring. PMID:24826025

  19. Novel bioequivalence approach for narrow therapeutic index drugs.

    PubMed

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

    2015-03-01

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

  20. Therapeutic enhancement of newly derived bacteriocins against Giardia lamblia.

    PubMed

    Amer, Eglal I; Mossallam, Shereen F; Mahrous, Hoda

    2014-11-01

    Trials for identifying efficient anti-giardial agents are still ongoing. Nowadays, bacteriocins have attracted the attention as potential antimicrobial compounds. For the first time, the current study evaluated the therapeutic efficacy of bacteriocins derived from newly isolated Egyptian strains of probiotics Lactobacilli; L. acidophilus (P106) and L. plantarum (P164) against Giardia lamblia. Bacteriocins' efficacy was evaluated both in vitro; by growth inhibition and adherence assays, and in vivo; through estimation of parasite density, intestinal histopathological examination and ultrastructural analysis of Giardia trophozoites. In vivo bacteriocins' clinical safety was assessed. In vitro results proved that 50 µg of L. acidophilus bacteriocin induced reduction of the mean Giardia lamblia trophozoites by 58.3 ± 4.04%, while at lower concentrations of 10 and 20 µg of both L. acidophilus and L. plantarum, non significant reduction of the mean parasite density was achieved. In vitro trophozoites adherence was susceptible to the tested bacteriocins at all studied concentrations with variable degrees, while the highest adherence reduction was demonstrated using 50 µg of L acidophilus bacteriocin. In vivo, oral inoculation of 50 µg/mouse L. acidophilus bacteriocin for 5 successive days resulted in a noteworthy decline of the intestinal parasite density, along with amelioration of intestinal pathology of infected mice. Ultrastructural examination proved thatfive doses of L. acidophilus bacteriocin showed marked changes in cellular architecture of the trophozoites with evident disorganization of the cell membrane, adhesive disc and cytoplasmic components. This is the first reported study of the safe anti-giardial efficacy of L. acidophilus (P106) derived bacteriocin, hence highlighting its great promise as a potential therapeutic safe alternative to existing commercial drugs.

  1. The Therapeutic Roller Coaster

    PubMed Central

    CHU, JAMES A.

    1992-01-01

    Survivors of severe childhood abuse often encounter profound difficulties. In addition to posttraumatic and dissociative symptomatology, abuse survivors frequently have characterologic problems, particularly regarding self-care and maintaining relationships. Backgrounds of abuse, abandonment, and betrayal are often recapitulated and reenacted in therapy, making the therapeutic experience arduous and confusing for therapists and patients. Efforts must be directed at building an adequate psychotherapeutic foundation before undertaking exploration and abreaction of past traumatic experiences. This discussion sets out a model for treatment of childhood abuse survivors, describing stages of treatment and suggesting interventions. Common treatment dilemmas or "traps" are discussed, with recommendations for their resolution. PMID:22700116

  2. Achieving closure at Fernald

    SciTech Connect

    Bradburne, John; Patton, Tisha C.

    2001-02-25

    When Fluor Fernald took over the management of the Fernald Environmental Management Project in 1992, the estimated closure date of the site was more than 25 years into the future. Fluor Fernald, in conjunction with DOE-Fernald, introduced the Accelerated Cleanup Plan, which was designed to substantially shorten that schedule and save taxpayers more than $3 billion. The management of Fluor Fernald believes there are three fundamental concerns that must be addressed by any contractor hoping to achieve closure of a site within the DOE complex. They are relationship management, resource management and contract management. Relationship management refers to the interaction between the site and local residents, regulators, union leadership, the workforce at large, the media, and any other interested stakeholder groups. Resource management is of course related to the effective administration of the site knowledge base and the skills of the workforce, the attraction and retention of qualified a nd competent technical personnel, and the best recognition and use of appropriate new technologies. Perhaps most importantly, resource management must also include a plan for survival in a flat-funding environment. Lastly, creative and disciplined contract management will be essential to effecting the closure of any DOE site. Fluor Fernald, together with DOE-Fernald, is breaking new ground in the closure arena, and ''business as usual'' has become a thing of the past. How Fluor Fernald has managed its work at the site over the last eight years, and how it will manage the new site closure contract in the future, will be an integral part of achieving successful closure at Fernald.

  3. Therapeutic drug monitoring and tyrosine kinase inhibitors

    PubMed Central

    Herviou, Pauline; Thivat, Emilie; Richard, Damien; Roche, Lucie; Dohou, Joyce; Pouget, Mélanie; Eschalier, Alain; Durando, Xavier; Authier, Nicolas

    2016-01-01

    The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs. PMID:27446421

  4. Chloride extrusion enhancers as novel therapeutics for neurological diseases.

    PubMed

    Gagnon, Martin; Bergeron, Marc J; Lavertu, Guillaume; Castonguay, Annie; Tripathy, Sasmita; Bonin, Robert P; Perez-Sanchez, Jimena; Boudreau, Dominic; Wang, Bin; Dumas, Lionel; Valade, Isabelle; Bachand, Karine; Jacob-Wagner, Mariève; Tardif, Christian; Kianicka, Irenej; Isenring, Paul; Attardo, Giorgio; Coull, Jeffrey A M; De Koninck, Yves

    2013-11-01

    The K(+)-Cl(-) cotransporter KCC2 is responsible for maintaining low Cl(-) concentration in neurons of the central nervous system (CNS), which is essential for postsynaptic inhibition through GABA(A) and glycine receptors. Although no CNS disorders have been associated with KCC2 mutations, loss of activity of this transporter has emerged as a key mechanism underlying several neurological and psychiatric disorders, including epilepsy, motor spasticity, stress, anxiety, schizophrenia, morphine-induced hyperalgesia and chronic pain. Recent reports indicate that enhancing KCC2 activity may be the favored therapeutic strategy to restore inhibition and normal function in pathological conditions involving impaired Cl(-) transport. We designed an assay for high-throughput screening that led to the identification of KCC2 activators that reduce intracellular chloride concentration ([Cl(-)]i). Optimization of a first-in-class arylmethylidine family of compounds resulted in a KCC2-selective analog (CLP257) that lowers [Cl(-)]i. CLP257 restored impaired Cl(-) transport in neurons with diminished KCC2 activity. The compound rescued KCC2 plasma membrane expression, renormalized stimulus-evoked responses in spinal nociceptive pathways sensitized after nerve injury and alleviated hypersensitivity in a rat model of neuropathic pain. Oral efficacy for analgesia equivalent to that of pregabalin but without motor impairment was achievable with a CLP257 prodrug. These results validate KCC2 as a druggable target for CNS diseases.

  5. Mechanisms of Plasma Therapeutics

    NASA Astrophysics Data System (ADS)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  6. Therapeutic endoscopy in gastroenterology.

    PubMed

    Celiński, K; Cichoz-Lach, H

    2007-08-01

    The role of therapeutic endoscopy in current gastroenterology is very important. Therapuetic endoscopy is useful in treatment of gastrointestinal bleeding. Endoscopic control of gastrointestinal bleeding includes the following procedures of haemostasis techniques: photocoagulation, electrocoagulation, thermocoagulation and injection method. Owing to these procedures mortality has significantly decreased. Endoscopic hemostasis eliminates the risk of surgery, is less expensive and better tolerated by patients. Colonoscopic polypectomy is a widely used technique. By removal of polyps the incidence of colon cancer can be decreased. The "hot biopsy" forceps can be used to excise polyps of up to 6 mm. Larger polyps can be removed safely by snare electrocautery and retrieved for histologic study. Endoscopic retrograde cholangiopancreatography has a therapeutic application designed to cut the sphincter of Oddi fibers of the distal common bile duct, what is indicated currently in choledocholithiasis and papillary stenosis with ascending cholangitis, acute gallstone pancreatitis. Endoscopic sphincterotomy in now an established procedure that is indicated in patients with common bile duct calculi. Endoscopic decompression of the biliary tree - dilatation benign structures of the biliary tree with baloon catheters and placement an internal endoprothesis allows the nonoperative decompression and significant palliation for patients with obstructing tumors.

  7. Person-centered Therapeutics

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many challenges. The Temperament and Character Inventory (TCI) provides an effective way to describe personality thoroughly and to predict both the positive and negative aspects of health. Strengths and weaknesses in TCI personality traits allow strong predictions of individual differences of all aspects of well-being. Diverse therapeutic techniques, such as diet, exercise, mood self-regulation, meditation, or acts of kindness, influence health and personality development in ways that are largely indistinguishable from one another or from effective allopathic treatments. Hence the development of well-being appears to be the result of activating a synergistic set of mechanisms of well-being, which are expressed as fuller functioning, plasticity, and virtue in adapting to life’s challenges PMID:26052429

  8. Engineering therapeutic protein disaggregases

    PubMed Central

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  9. Nitrones as Therapeutics

    PubMed Central

    Floyd, Robert A.; Kopke, Richard D.; Choi, Chul-Hee; Foster, Steven B.; Doblas, Sabrina; Towner, Rheal A.

    2008-01-01

    Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes can not readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our observations and others where the use of selected nitrones as novel therapeutics have been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases. PMID:18793715

  10. Review of "Our Immense Achievement Gap"

    ERIC Educational Resources Information Center

    Eaton, Susan

    2012-01-01

    This report misrepresents and then criticizes recommendations from the Minnesota Department of Education, a think tank and two independent study groups, each of which recently encouraged particular voluntary efforts to reduce concentrated poverty and achieve racial and socioeconomic integration in schools and housing in Minnesota. In building its…

  11. Therapeutic targeting of replicative immortality.

    PubMed

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy.

  12. Therapeutic targeting of replicative immortality

    PubMed Central

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S. Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  13. Materials innovation for co-delivery of diverse therapeutic cargos

    PubMed Central

    Godsey, Megan E; Suryaprakash, Smruthi; Leong, Kam W

    2014-01-01

    Co-delivery is a rapidly growing sector of drug delivery that aspires to enhance therapeutic efficacy through controlled delivery of diverse therapeutic cargoes with synergistic activities. It requires the design of carriers capable of simultaneously transporting to and releasing multiple therapeutics at a disease site. Co-delivery has arisen from the emerging trend of combination therapy, where treatment with two or more therapeutics at the same time can succeed where single therapeutics fail. However, conventional combination therapy offers little control over achieving an optimized therapeutic ratio at the target site. Co-delivery via inclusion of multiple therapeutic cargos within the same carrier addresses this issue by not only ensuring delivery of both therapeutics to the same cell, but also offering a platform for control of the delivery process, from loading to release. Co-delivery systems have been formulated using a number of carriers previously developed for single-therapeutic delivery. Liposomes, polymeric micelles, PLGA nanoparticles, and dendrimers have all been adapted for co-delivery. Much of the effort focuses on dealing with drugs having dissimilar properties, increasing loading efficiencies, and controlling loading and release ratios. In this review, we highlight the innovations in carrier designs and formulations to deliver combination cargoes of drug/drug, drug/siRNA, and drug/pDNA toward disease therapy. With rapid advances in mechanistic understanding of interrelating molecular pathways and development of molecular medicine, the future of co-delivery will become increasingly promising and prominent. PMID:24818000

  14. Achievement Goals and Achievement Emotions: A Meta-Analysis

    ERIC Educational Resources Information Center

    Huang, Chiungjung

    2011-01-01

    This meta-analysis synthesized 93 independent samples (N = 30,003) in 77 studies that reported in 78 articles examining correlations between achievement goals and achievement emotions. Achievement goals were meaningfully associated with different achievement emotions. The correlations of mastery and mastery approach goals with positive achievement…

  15. The relationship between patients' educational level and therapeutic process in an acute patient therapeutic community.

    PubMed

    Isohanni, I; Nieminen, P; Isohanni, M

    1997-01-01

    Traditional custodial care in mental hospitals has given way to brief hospitalizations and a variety of active inpatient treatment milieus, eg, therapeutic communities. But can only well-educated patients utilize this kind of complex, even demanding form of psychosocial care? A total of 1,538 patients and their first admissions from 1977 to 1993 at a closed therapeutic community ward at the Department of Psychiatry, University of Oulu (Finland) were assessed to analyze the association of the patient's educational level with some treatment and outcome characteristics. Educational levels were non-professional education (46% of all patients), lower professional (39%) and higher professional education (15%). There were no statistically significant differences in the treatment and outcome variables of patients in any educational level. The result indicates the achievement of one treatment goal on the therapeutic community model, ie, patient equality in spite of different educational status. This result may be especially important for less educated persons.

  16. Therapeutic interventions in acute stroke.

    PubMed Central

    Lees, K R

    1992-01-01

    1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; intravenous glycerol is unproven. 3. Haemodilution to reduce whole blood viscosity and improve perfusion is ineffective. Thrombolytic drugs have not been adequately tested but several randomised multicentre trials are now commencing. Early treatment and CT scanning are essential. 4. Anticoagulants and antiplatelet drugs may have wide applicability but have not been tested in the acute phase of stroke. A multi-centre trial will address this issue. 5. Neuronal cytoprotection offers exciting prospects for acute stroke treatment. Antagonists of glutamate at the NMDA receptor, calcium and sodium channel blocking agents and free radical scavenging drugs have potent effects experimentally. Several agents are now reaching clinical trials. The calcium antagonist nimodipine has been disappointing in large scale trials but some studies were flawed by late treatment. 6. Successful treatment of acute stroke is likely to combine several approaches. 7. Therapeutic trials in stroke must include CT scanning, early treatment and a multicentre approach to achieve large numbers of patients. PMID:1493080

  17. Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

    PubMed Central

    Youn, Gilmer; Jones, Brenda; Jelliffe, Roger W.; Drusano, George L.; Rodvold, Keith A.; Lodise, Thomas P.

    2014-01-01

    The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter. PMID:24165176

  18. High-efficiency solar concentrator

    NASA Technical Reports Server (NTRS)

    Lansing, F. L.; Dorman, J.

    1976-01-01

    A new type of solar concentrator is presented using liquid lenses and simple translational tracking mechanism. The concentrator achieves a 100:1 nominal concentration ratio and is compared in performance with a flat-plate collector having two sheets of glazing and non-selective coating. The results of the thermal analysis show that higher temperatures can be obtained with the concentrator than is possible with the non-concentrator flat-plate type. Furthermore, the thermal efficiency far exceeds that of the comparative flat-plate type for all operating conditions.

  19. High-efficiency solar concentrator

    NASA Technical Reports Server (NTRS)

    Lansing, F. L.; Dorman, J.

    1980-01-01

    A new type of solar concentrator is presented using liquid lenses and simple translational tracking mechanism. The concentrator achieves a 100:1 nominal concentration ratio and is compared in performance with a flat-plate collector having two sheets of glazing and non-selective coating. The results of the thermal analysis show that higher temperatures can be obtained with the concentrator than is possible with the non-concentrator flat-plate type. Furthermore, the thermal efficiency far exceeds that of the comparative flat-plate type for all operating conditions.

  20. Combined approach with therapeutic drug monitoring and pharmacogenomics in renal transplant recipients.

    PubMed

    Manvizhi, S; Mathew, B S; Fleming, D H; Basu, G; John, G T

    2013-01-01

    In patients undergoing renal transplantation, dose individualization for tacrolimus is routinely achieved with therapeutic drug monitoring (TDM). The patient started on 5.5 mg/day of tacrolimus had a significantly elevated tacrolimus trough concentration. The tacrolimus dose was regularly reduced following TDM at many time periods in the post transplant period but the tacrolimus concentration was consistently elevated. Genomic analysis done after four years revealed mutations in the genes encoding for CYP3A5 and MDR1 (2677G > T). Pharmacogenomics alongside TDM, will soon emerge as the backbone of dose individualization. But for genomics to be beneficial, it should be advocated in the pre-transplant or early post transplant period.

  1. Therapeutic oligonucleotides and delivery technologies: Research topics in Japan.

    PubMed

    Murakami, Masahiro

    2016-01-01

    Oligonucleotides have been gaining considerable attention as promising and effective candidate therapeutics against various diseases. This special issue is aimed at providing a better understanding of the recent progress in the development of oligonucleotide-based therapeutics to encourage further research and innovation in this field to achieve these advancements. Several Japanese scientists have been invited to contribute to this issue by describing their recent findings, overviews, insights, or commentaries on rational designing of therapeutic oligonucleotide molecules and their novel delivery technologies, especially nanocarrier systems.

  2. Fairy tales as a trance experience: possible therapeutic uses.

    PubMed

    Stevens-Guille, M E; Boersma, F J

    1992-04-01

    The psychological literature contains little documentation of the therapeutic use of fairy tales. We suggest that fairy tales are uniquely suitable for hypnotherapy and for helping clients reframe existential issues. We propose that the structure of fairy tales allows the meaning of the story to be applied personally and that they also stimulate unconscious search. We examine the way in which hypnosis is achieved when fairy tales are read to children, as well as possible therapeutic uses of this learning set in therapy with both children and adults. We conclude by suggesting that fairy tales need to be given serious consideration as an alternative therapeutic trance procedure.

  3. Antibody Engineering and Therapeutics

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  4. Outpatient therapeutic nuclear oncology.

    PubMed

    Turner, J Harvey

    2012-05-01

    In the beginning, nuclear medicine was radionuclide therapy, which has evolved into molecular tumour-targeted control of metastatic cancer. Safe, efficacious, clinical practice of therapeutic nuclear oncology may now be based upon accurate personalised dosimetry by quantitative gamma SPECT/CT imaging to prescribe tumoricidal activities without critical organ toxicity. Preferred therapy radionuclides possess gamma emission of modest energy and abundance to enable quantitative SPECT/CT imaging for calculation of the beta therapy dosimetry, without radiation exposure risk to hospital personnel, carers, family or members of the public. The safety of outpatient radiopharmaceutical therapy of cancer with Iodine-131, Samarium-153, Holmium-166, Rhenium-186, Rhenium-188, Lutetium-177 and Indium-111 is reviewed. Measured activity release rates and radiation exposure to carers and the public are all within recommendations and guidelines of international regulatory agencies and, when permitted by local regulatory authorities allow cost-effective, safe, outpatient radionuclide therapy of cancer without isolation in hospital.

  5. Mitochondrial Energetics and Therapeutics

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei; Procaccio, Vincent

    2011-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics. PMID:20078222

  6. Antimicrobial peptides: therapeutic potentials.

    PubMed

    Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

    2014-12-01

    The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.

  7. Aptamers in Therapeutics

    PubMed Central

    2016-01-01

    Aptamers are single strand DNA or RNA molecules, selected by an iterative process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to various advantages of aptamers such as high temperature stability, animal free, cost effective production and its high affinity and selectivity for its target make them attractive alternatives to monoclonal antibody for use in diagnostic and therapeutic purposes. Aptamer has been generated against vesicular endothelial growth factor 165 involved in age related macular degeneracy. Macugen was the first FDA approved aptamer based drug that was commercialized. Later other aptamers were also developed against blood clotting proteins, cancer proteins, antibody E, agents involved in diabetes nephropathy, autoantibodies involved in autoimmune disorders, etc. Aptamers have also been developed against viruses and could work with other antiviral agents in treating infections. PMID:27504277

  8. Microfabricated therapeutic actuators

    DOEpatents

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  9. Microfabricated therapeutic actuators

    DOEpatents

    Lee, A.P.; Northrup, M.A.; Ciarlo, D.R.; Krulevitch, P.A.; Benett, W.J.

    1999-06-15

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use. 8 figs.

  10. Race-based therapeutics.

    PubMed

    Yancy, Clyde W

    2008-08-01

    The issue of race in medicine is problematic. Race is not a physiologic grouping, and all persons of a given race do not necessarily share the same clinical phenotype or genetic substrate. Despite clear signals that certain risk factors and diseases vary as a function of race, translating those differences into race-based therapeutics has been awkward and has done little to change the natural history of cardiovascular disease as it affects special populations. Among the varied special populations, the African American population appears to have the most significant and adverse variances for cardiovascular disease as well as worrisome signals that drug responsiveness varies. Recent guideline statements have now acknowledged certain treatment options that are most appropriate for African Americans with cardiovascular disease, especially hypertension and heart failure. As more physiologic markers of disease and drug responsiveness become available, the need for racial designations in medicine may lessen, and therapies can be optimized for all patients without regard to race or ethnicity.

  11. Airborne agent concentration analysis

    DOEpatents

    Gelbard, Fred

    2004-02-03

    A method and system for inferring airborne contaminant concentrations in rooms without contaminant sensors, based on data collected by contaminant sensors in other rooms of a building, using known airflow interconnectivity data. The method solves a least squares problem that minimizes the difference between measured and predicted contaminant sensor concentrations with respect to an unknown contaminant release time. Solutions are constrained to providing non-negative initial contaminant concentrations in all rooms. The method can be used to identify a near-optimal distribution of sensors within the building, when then number of available sensors is less than the total number of rooms. This is achieved by having a system-sensor matrix that is non-singular, and by selecting that distribution which yields the lowest condition number of all the distributions considered. The method can predict one or more contaminant initial release points from the collected data.

  12. A panic attack in therapeutic recreation over being considered therapeutic.

    PubMed

    Lee, L L

    1987-01-01

    Ancillary professions have been called upon to account for therapeutic benefits from their services or be eliminated from the health care system. A singular focus on therapy, however, would negate the unique contribution of therapeutic recreation within, while simultaneously restricting services to health care settings. It is proposed that panic over therapeutic recreation services meeting health care goals has hindered evaluation and solidification of the leisure-based philosophy presented in the NTRS Philosophical Position Statement (NTRS, 1982). It is argued that emphasizing the leisure orientation of the philosophical position statement can secure therapeutic recreation's position within, yet, not deny services to those outside of the health care system. An overview is presented on the adequacy of the position statement philosophy for therapeutic recreation. A potential danger of attempting to explain therapeutic recreation in terms of non-leisure based philosophies is also discussed.

  13. Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels)

    PubMed Central

    Schaefer, Elizabeth; Walsh, Mary; Newman, Donna; Salmon, Jacklyn; Amin, Rasidul; Weiss, Sidney; Grau, Ulrich; Velagaleti, Poonam

    2016-01-01

    Objective. To evaluate thermosensitive, biodegradable pentablock copolymers (PTSgel) for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods. Five PTSgels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTSgels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTSgel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTSgel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results. IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTSgel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTSgels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo. Conclusions. Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTSgel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTSgel remains after drug release is complete. PMID:27800184

  14. Engineered therapeutic-releasing nanoporous anodic alumina-aluminum wires with extended release of therapeutics.

    PubMed

    Law, Cheryl Suwen; Santos, Abel; Kumeria, Tushar; Losic, Dusan

    2015-02-18

    In this study, we present a nanoengineered therapeutic-releasing system based on aluminum wires featuring nanoporous anodic alumina layers and chitosan coatings. Nanoporous anodic alumina layers are produced on the surface of aluminum wires by electrochemical anodization. These nanoporous layers with precisely engineered nanopore geometry are used as nanocontainers for bovine serum albumin molecules labeled with fluorescein isothiocyanate (BSA-FITC), which is selected as a model drug. The surface of these therapeutic-releasing implants is coated with a biocompatible and biodegradable polymer, chitosan, in order to achieve a sustained release of protein over extended periods of time. The performance of this therapeutic-releasing device is systematically assessed through a series of experiments under static and dynamic flow conditions. In these experiments, the effect of such parameters as the number of layers of chitosan coating and the temperature and pH of the eluting medium is established. The obtained results reveal that the proposed therapeutic-releasing system based on nanoporous aluminum wires can be engineered with sustained release performance for up to 6.5 weeks, which is a critical factor for medical treatments using sensitive therapeutics such as proteins and genes when a localized delivery is desired.

  15. [Nuclear transfer and therapeutic cloning].

    PubMed

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  16. Therapeutic use of nicergoline.

    PubMed

    Winblad, Bengt; Fioravanti, Mario; Dolezal, Tomas; Logina, Inara; Milanov, Ivan Gospodinov; Popescu, Dinu Cristian; Solomon, Alina

    2008-01-01

    The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are

  17. Lifting Minority Achievement: Complex Answers. The Achievement Gap.

    ERIC Educational Resources Information Center

    Viadero, Debra; Johnston, Robert C.

    2000-01-01

    This fourth in a four-part series on why academic achievement gaps exist describes the Minority Achievement Committee scholars program at Shaker Heights High School in Cleveland, Ohio, a powerful antidote to the achievement gap between minority and white and Asian American students. It explains the need to break down stereotypes about academic…

  18. Achievement Motivation of Women: Effects of Achievement and Affiliation Arousal.

    ERIC Educational Resources Information Center

    Gama, Elizabeth Maria Pinheiro

    1985-01-01

    Assigned 139 Brazilian women to neutral, affiliation arousal, and achievement arousal conditions based on their levels of achievement (Ach) and affiliative (Aff) needs. Results of story analyses revealed that achievement arousal increased scores of high Ach subjects and that high Aff subjects obtained higher scores than low Aff subjects. (BL)

  19. Attitude Towards Physics and Additional Mathematics Achievement Towards Physics Achievement

    ERIC Educational Resources Information Center

    Veloo, Arsaythamby; Nor, Rahimah; Khalid, Rozalina

    2015-01-01

    The purpose of this research is to identify the difference in students' attitude towards Physics and Additional Mathematics achievement based on gender and relationship between attitudinal variables towards Physics and Additional Mathematics achievement with achievement in Physics. This research focused on six variables, which is attitude towards…

  20. The Impact of Reading Achievement on Overall Academic Achievement

    ERIC Educational Resources Information Center

    Churchwell, Dawn Earheart

    2009-01-01

    This study examined the relationship between reading achievement and achievement in other subject areas. The purpose of this study was to determine if there was a correlation between reading scores as measured by the Standardized Test for the Assessment of Reading (STAR) and academic achievement in language arts, math, science, and social studies…

  1. 'Smartening' anticancer therapeutic nanosystems using biomolecules.

    PubMed

    Núñez-Lozano, Rebeca; Cano, Manuel; Pimentel, Belén; de la Cueva-Méndez, Guillermo

    2015-12-01

    To be effective, anticancer agents must induce cell killing in a selective manner, something that is proving difficult to achieve. Drug delivery systems could help to solve problems associated with the lack of selectivity of classical chemotherapeutic agents. However, to realize this, such systems must overcome multiple physiological barriers. For instance, they must evade surveillance by the immune system, attach selectively to target cells, and gain access to their interior. Furthermore, there they must escape endosomal entrapment, and release their cargoes in a controlled manner, without affecting their functionality. Here we review recent efforts aiming at using biomolecules to confer these abilities to bare nanoparticles, to transform them into smart anticancer therapeutic nanosystems.

  2. Therapeutic cloning: The ethical limits

    SciTech Connect

    Whittaker, Peter A. . E-mail: p.whittaker@lancaster.ac.uk

    2005-09-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated.

  3. Clinical applications of therapeutic phlebotomy

    PubMed Central

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. PMID:27486346

  4. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  5. Therapeutic antibody technology 97.

    PubMed

    Larrick, J W; Gavilondo, J

    1998-01-01

    Almost 200 antibody aficionados attended the Therapeutic Antibody Technology 97 meeting, held September 21-24, 1997 at the Holiday Inn, Union Square in the heart of San Francisco, CA. The meeting was sponsored by the Palo Alto Institute of Molecular Medicine and organized by James W. Larrick (PAIMM) and Dennis R. Burton (Scripps Research Institute). The meeting featured excellent discussions on many interesting talks and a number of poster presentations. It is likely that another meeting will be organized in 2 years, however in the meantime, an effort is underway to organize a 'Virtual Antibody Society' to be set up on the web server at Scripps Research Institute in La Jolla, CA (Questions and comments on this project can be sent to: Jwlarrick@aol.com or Burton@scripps.edu). Richard Lerner (Scripps) gave the keynote address on 'Catalytic Antibodies', describing recent work with Carlos Barbas on so-called reactive immunization to generate a high activity aldolase catalytic antibody. This antibody, soon to be described in an article in Science, is the first commercially available catalytic antibody.

  6. Leech Therapeutic Applications

    PubMed Central

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  7. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  8. Triggered Nanoparticles as Therapeutics

    PubMed Central

    Kim, Chang Soo; Duncan, Bradley; Creran, Brian; Rotello, Vincent M.

    2013-01-01

    Summary Drug delivery systems (DDSs) face several challenges including site-specific delivery, stability, and the programmed release of drugs. Engineered nanoparticle (NP) surfaces with responsive moieties can enhance the efficacy of DDSs for in vitro and in vivo systems. This triggering process can be achieved through both endogenous (biologically controlled release) and exogenous (external stimuli controlled release) activation. In this review, we will highlight recent examples of the use of triggered release strategies of engineered nanomaterials for in vitro and in vivo applications. PMID:24159362

  9. [Therapeutic strategies in the first psychotic episode].

    PubMed

    Douki, S; Taktak, M J; Ben Zineb, S; Cheour, M

    1999-11-01

    A first psychotic episode includes a wide range of disorders with different outcomes: schizophrenia, bipolar disorder, schizophreniform disorder, schizoaffective disorder, drug-induced psychosis, brief reactive psychosis, organic psychoses and delusional disorder. The course and outcome of a first psychotic episode is greatly dependent on its initial management. Major clinical, etiopathogenic and therapeutic advances have been achieved in this field and have allowed specific management strategies to be adopted. The primary task of therapists involved in the management of patients who have experienced a first episode of psychosis is promotion of recovery and prevention of secondary morbidity, relapse and persistent disability. The main guidelines of an early psychosis management are:--to keep in mind that early psychosis is not early schizophrenia. Thus, clinicians and therapists should avoid an early diagnosis of schizophrenia. Diagnosis in early psychosis can be highly unstable. A diagnosis of schizophrenia, with its implications of pessimism, relapse and disability, does not contribute anything positive in terms of guiding treatment. On the contrary, such a diagnosis may damage the patient and family by stigmatizing them and affecting the way they are viewed and managed by healthcare professionals.--To integrate biological, psychological and social interventions: effective medications is useful in reducing the risk of relapse, but is not a guarantee against it. Psychological and social interventions can greatly help promote recovery.--To tailor the various strategies to met the needs of an individual: as an example, it is important to formulate appropriate strategies for the different stages of the illness (prodromal phase, acute phase, early recovery phase and late recovery phase) because patients have different therapeutic needs at each stage.--In the acute treatment, not to concentrate on short-term goals in indicating antipsychotic treatment: prescribing

  10. Inhibition of AMP deaminase as therapeutic target in cardiovascular pathology.

    PubMed

    Zabielska, Magdalena A; Borkowski, Tomasz; Slominska, Ewa M; Smolenski, Ryszard T

    2015-08-01

    AMP deaminase (AMPD; EC 3.5.4.6) catalyzes hydrolysis of the amino group from the adenine ring of AMP resulting in production of inosine 5'-monophosphate (IMP) and ammonia. This reaction helps to maintain healthy cellular energetics by removing excess AMP that accumulates in energy depleted cells. Furthermore, AMPD permits the synthesis of guanine nucleotides from the larger adenylate pool. This enzyme competes with cytosolic 5'-nucleotidases (c5NT) for AMP. Adenosine, a product of c5NT is a vasodilator, antagonizes inotropic effects of catecholamines and exerts anti-platelet, anti-inflammatory and immunosuppressive activities. The ratio of AMPD/c5NT defines the amount of adenosine produced in adenine nucleotide catabolic pathway. Inhibition of AMPD could alter this ratio resulting in increased adenosine production. Besides the potential effect on adenosine production, elevation of AMP due to inhibition of AMPD could also lead to activation of AMP regulated protein kinase (AMPK) with myriad of downstream events including enhanced energetic metabolism, mitochondrial biogenesis and cytoprotection. While the benefits of these processes are well appreciated in cells such as skeletal or cardiac myocytes its role in protection of endothelium could be even more important. Therapeutic use of AMPD inhibition has been limited due to difficulties with obtaining compounds with adequate characteristics. However, endothelium seems to be the easiest target as effective inhibition of AMPD could be achieved at much lower concentration than in the other types of cells. New generation of AMPD inhibitors has recently been established and its testing in context of endothelial and organ protection could provide important basic knowledge and potential therapeutic tools.

  11. Therapeutic phytogenic compounds for obesity and diabetes.

    PubMed

    Jung, Hee Soong; Lim, Yun; Kim, Eun-Kyoung

    2014-11-21

    Natural compounds have been used to develop drugs for many decades. Vast diversities and minimum side effects make natural compounds a good source for drug development. However, the composition and concentrations of natural compounds can vary. Despite this inconsistency, half of the Food and Drug Administration (FDA)-approved pharmaceuticals are natural compounds or their derivatives. Therefore, it is essential to continuously investigate natural compounds as sources of new pharmaceuticals. This review provides comprehensive information and analysis on natural compounds from plants (phytogenic compounds) that may serve as anti-obesity and/or anti-diabetes therapeutics. Our growing understanding and further exploration of the mechanisms of action of the phytogenic compounds may afford opportunities for development of therapeutic interventions in metabolic diseases.

  12. Therapeutic Phytogenic Compounds for Obesity and Diabetes

    PubMed Central

    Jung, Hee Soong; Lim, Yun; Kim, Eun-Kyoung

    2014-01-01

    Natural compounds have been used to develop drugs for many decades. Vast diversities and minimum side effects make natural compounds a good source for drug development. However, the composition and concentrations of natural compounds can vary. Despite this inconsistency, half of the Food and Drug Administration (FDA)-approved pharmaceuticals are natural compounds or their derivatives. Therefore, it is essential to continuously investigate natural compounds as sources of new pharmaceuticals. This review provides comprehensive information and analysis on natural compounds from plants (phytogenic compounds) that may serve as anti-obesity and/or anti-diabetes therapeutics. Our growing understanding and further exploration of the mechanisms of action of the phytogenic compounds may afford opportunities for development of therapeutic interventions in metabolic diseases. PMID:25421245

  13. Cholangiocarcinoma: Molecular Pathways and Therapeutic Opportunities

    PubMed Central

    Rizvi, Sumera; Borad, Mitesh J.; Patel, Tushar; Gores, Gregory J.

    2015-01-01

    Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with limited treatment options and low survival rates. Currently, there are no curative medical therapies for CCA. Recent advances have enhanced our understanding of the genetic basis of this disease, and elucidated therapeutically relevant targets. Therapeutic efforts in development are directed at several key pathways due to genetic aberrations including receptor tyrosine kinase pathways, mutant IDH enzymes, the PI3K-AKT-mTOR pathway, and chromatin remodeling networks. A highly desmoplastic, hypovascular stroma is characteristic of CCAs and recent work has highlighted the importance of targeting this pathway via stromal myofibroblast depletion. Future efforts should concentrate on combination therapies with action against the cancer cell and the surrounding tumor stroma. As the mutational landscape of CCA is being illuminated, molecular profiling of patient tumors will enable identification of specific mutations and the opportunity to offer directed, personalized treatment options. PMID:25369307

  14. [Level of evidence for therapeutic drug monitoring for paclitaxel].

    PubMed

    Gerritsen-van Schieveen, Pauline; Royer, Bernard

    2010-01-01

    Paclitaxel is an anticancer drug which displays pharmacokinetic properties which can lead to therapeutic drug monitoring requirement. The most effective pharmacokinetic parameter seems to be the time during which the plasma concentration is over 0.05 micromol/L. However, this target needs to be validated with new weekly schedules of administration. These reasons lead to consider the level of evidence of therapeutic drug monitoring of paclitaxel as potentially useful.

  15. When not to trust therapeutic drug monitoring

    PubMed Central

    Westergreen-Thorne, Mathew; Lee, Sook Yan; Shah, Nilesh; Dodd, Alan

    2016-01-01

    Therapeutic drug monitoring (TDM) is the measurement of serum or plasma drug concentration to allow the individualization of dosing. We describe the case of a patient who was prescribed inappropriately large doses of vancomycin due to inaccurate TDM. Specifically, our laboratory reported progressively lower vancomycin concentrations despite dose increases. Eventually, when duplicate samples were sent to a different laboratory vancomycin concentrations were found to be in the toxic range. We hypothesize this was due to the patient generating immunoglobulin antibodies against her infection that interfered with the original TDM immunoassay. Immunogenic TDM interference has been known to rarely occur in patients with immune related comorbidities; however, if we are correct, this is a unique case as this patient did not have such a background. This case illustrates the importance of using clinical judgement when interpreting TDM as, in this case, substantial harm to the patient was likely only narrowly avoided. PMID:27606069

  16. Achievements in Stratospheric Ozone Protection

    EPA Pesticide Factsheets

    This report describes achievements in protecting the ozone layer, the benefits of these achievements, and strategies involved (e.g., using alternatives to ozone-depleting substances, phasing out harmful substances, and creating partnerships).

  17. Magnetic Microspheres for Therapeutical Applications

    NASA Technical Reports Server (NTRS)

    Mazuruk, K.; Ramachandran, N.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady. The basic obstacle of the present heating methods are non-uniform thermal properties of the tissue. Our approach is to develop a novel class of magnetic fluids which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as a suitable nano-particle material. The objective is to synthesize, characterize and evaluate the efficacy of TRMF for hyperthermia therapy.

  18. Concentrated Solar Thermoelectric Power

    SciTech Connect

    Chen, Gang; Ren, Zhifeng

    2015-07-09

    The goal of this project is to demonstrate in the lab that solar thermoelectric generators (STEGs) can exceed 10% solar-to-electricity efficiency, and STEGs can be integrated with phase-change materials (PCM) for thermal storage, providing operation beyond daylight hours. This project achieved significant progress in many tasks necessary to achieving the overall project goals. An accurate Themoelectric Generator (TEG) model was developed, which included realistic treatment of contact materials, contact resistances and radiative losses. In terms of fabricating physical TEGs, high performance contact materials for skutterudite TE segments were developed, along with brazing and soldering methods to assemble segmented TEGs. Accurate measurement systems for determining device performance (in addition to just TE material performance) were built for this project and used to characterize our TEGs. From the optical components’ side, a spectrally selective cermet surface was developed with high solar absorptance and low thermal emittance, with thermal stability at high temperature. A measurement technique was also developed to determine absorptance and total hemispherical emittance at high temperature, and was used to characterize the fabricated spectrally selective surfaces. In addition, a novel reflective cavity was designed to reduce radiative absorber losses and achieve high receiver efficiency at low concentration ratios. A prototype cavity demonstrated that large reductions in radiative losses were possible through this technique. For the overall concentrating STEG system, a number of devices were fabricated and tested in a custom built test platform to characterize their efficiency performance. Additionally, testing was performed with integration of PCM thermal storage, and the storage time of the lab scale system was evaluated. Our latest testing results showed a STEG efficiency of 9.6%, indicating promising potential for high performance concentrated STEGs.

  19. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  20. Mitochondrial diseases: therapeutic approaches.

    PubMed

    DiMauro, Salvatore; Mancuso, Michelangelo

    2007-06-01

    Therapy of mitochondrial encephalomyopathies (defined restrictively as defects of the mitochondrial respiratory chain) is woefully inadequate, despite great progress in our understanding of the molecular bases of these disorders. In this review, we consider sequentially several different therapeutic approaches. Palliative therapy is dictated by good medical practice and includes anticonvulsant medication, control of endocrine dysfunction, and surgical procedures. Removal of noxious metabolites is centered on combating lactic acidosis, but extends to other metabolites. Attempts to bypass blocks in the respiratory chain by administration of electron acceptors have not been successful, but this may be amenable to genetic engineering. Administration of metabolites and cofactors is the mainstay of real-life therapy and is especially important in disorders due to primary deficiencies of specific compounds, such as carnitine or coenzyme Q10. There is increasing interest in the administration of reactive oxygen species scavengers both in primary mitochondrial diseases and in neurodegenerative diseases directly or indirectly related to mitochondrial dysfunction. Aerobic exercise and physical therapy prevent or correct deconditioning and improve exercise tolerance in patients with mitochondrial myopathies due to mitochondrial DNA (mtDNA) mutations. Gene therapy is a challenge because of polyplasmy and heteroplasmy, but interesting experimental approaches are being pursued and include, for example, decreasing the ratio of mutant to wild-type mitochondrial genomes (gene shifting), converting mutated mtDNA genes into normal nuclear DNA genes (allotopic expression), importing cognate genes from other species, or correcting mtDNA mutations with specific restriction endonucleases. Germline therapy raises ethical problems but is being considered for prevention of maternal transmission of mtDNA mutations. Preventive therapy through genetic counseling and prenatal diagnosis is

  1. The Evolution of Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Riley, Bob; Skalko, Thomas K.

    1998-01-01

    Reviews elements that impact the delivery of therapeutic recreation services, emphasizing elements that are external to the discipline and influence practice and elements that are internal to the discipline and must be addressed if therapeutic recreation is to continue its evolution as a competitive health and human service discipline.…

  2. Toward Constructing the Therapeutic System.

    ERIC Educational Resources Information Center

    Andolfi, Maurizio; Angelo, Claudio

    1988-01-01

    Describes the therapist as an active participant in the construction of the therapeutic system, explaining how the therapist constructs complex relationships within the evolving therapeutic process. Reevaluates the importance of the individual in the family as an agent of change and as a mediator of triangular relational messages. (Author/NB)

  3. Students’ Achievement Goals, Learning-Related Emotions and Academic Achievement

    PubMed Central

    Lüftenegger, Marko; Klug, Julia; Harrer, Katharina; Langer, Marie; Spiel, Christiane; Schober, Barbara

    2016-01-01

    In the present research, the recently proposed 3 × 2 model of achievement goals is tested and associations with achievement emotions and their joint influence on academic achievement are investigated. The study was conducted with 388 students using the 3 × 2 Achievement Goal Questionnaire including the six proposed goal constructs (task-approach, task-avoidance, self-approach, self-avoidance, other-approach, other-avoidance) and the enjoyment and boredom scales from the Achievement Emotion Questionnaire. Exam grades were used as an indicator of academic achievement. Findings from CFAs provided strong support for the proposed structure of the 3 × 2 achievement goal model. Self-based goals, other-based goals and task-approach goals predicted enjoyment. Task-approach goals negatively predicted boredom. Task-approach and other-approach predicted achievement. The indirect effects of achievement goals through emotion variables on achievement were assessed using bias-corrected bootstrapping. No mediation effects were found. Implications for educational practice are discussed. PMID:27199836

  4. Therapeutic applications of hydrogels in oral drug delivery

    PubMed Central

    Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

    2015-01-01

    Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

  5. Metrics for antibody therapeutics development.

    PubMed

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  6. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  7. Bacteriophage Procurement for Therapeutic Purposes

    PubMed Central

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  8. Exubera. Inhale therapeutic systems.

    PubMed

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  9. Drug resistance confounding prion therapeutics

    PubMed Central

    Berry, David B.; Lu, Duo; Geva, Michal; Watts, Joel C.; Bhardwaj, Sumita; Oehler, Abby; Renslo, Adam R.; DeArmond, Stephen J.; Prusiner, Stanley B.; Giles, Kurt

    2013-01-01

    There is not a single pharmaceutical that halts or even slows any neurodegenerative disease. Mounting evidence shows that prions cause many neurodegenerative diseases, and arguably, scrapie and Creutzfeldt–Jakob disease prions represent the best therapeutic targets. We report here that the previously identified 2-aminothiazoles IND24 and IND81 doubled the survival times of scrapie-infected, wild-type mice. However, mice infected with Rocky Mountain Laboratory (RML) prions, a scrapie-derived strain, and treated with IND24 eventually exhibited neurological dysfunction and died. We serially passaged their brain homogenates in mice and cultured cells. We found that the prion strain isolated from IND24-treated mice, designated RML[IND24], emerged during a single passage in treated mice. Although RML prions infect both the N2a and CAD5 cell lines, RML[IND24] prions could only infect CAD5 cells. When passaged in CAD5 cells, the prions remained resistant to high concentrations of IND24. However, one passage of RML[IND24] prions in untreated mice restored susceptibility to IND24 in CAD5 cells. Although IND24 treatment extended the lives of mice propagating different prion strains, including RML, another scrapie-derived prion strain ME7, and chronic wasting disease, it was ineffective in slowing propagation of Creutzfeldt–Jakob disease prions in transgenic mice. Our studies demonstrate that prion strains can acquire resistance upon exposure to IND24 that is lost upon passage in mice in the absence of IND24. These data suggest that monotherapy can select for resistance, thus intermittent therapy with mixtures of antiprion compounds may be required to slow or stop neurodegeneration. PMID:24128760

  10. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  11. Nanoparticle-Based Delivery of RNAi Therapeutics: Progress and Challenges

    PubMed Central

    Zhou, Jiehua; Shum, Ka-To; Burnett, John C.; Rossi, John J.

    2013-01-01

    RNA interference (RNAi) is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. Although RNAi therapeutics have recently progressed through the pipeline toward clinical trials, the application of these as ideal, clinical therapeutics requires the development of safe and effective delivery systems. Inspired by the immense progress with nanotechnology in drug delivery, efforts have been dedicated to the development of nanoparticle-based RNAi delivery systems. For example, a precisely engineered, multifunctional nanocarrier with combined passive and active targeting capabilities may address the delivery challenges for the widespread use of RNAi as a therapy. Therefore, in this review, we introduce the major hurdles in achieving efficient RNAi delivery and discuss the current advances in applying nanotechnology-based delivery systems to overcome the delivery hurdles of RNAi therapeutics. In particular, some representative examples of nanoparticle-based delivery formulations for targeted RNAi therapeutics are highlighted. PMID:23667320

  12. Natural Products as Source of Therapeutics against Parasitic Diseases.

    PubMed

    Hertweck, Christian

    2015-12-01

    An end to suffering: Parasitic infections with protozoa and worms cause unimaginable misery, in particular in the tropics. Fortunately, natural products, such as the antimalarial artemisinin (1) and the anthelmintic avermectin (2) were discovered and developed into therapeutics. These major achievements now culminated in the 2015 Nobel Prize for Medicine.

  13. Molecular hydrogen: a therapeutic antioxidant and beyond

    PubMed Central

    Huang, Lei

    2016-01-01

    Molecular hydrogen (H2) medicine research has flourished since a landmark publication in Nature Medicine that revealed the antioxidant and cytoprotective effects of hydrogen gas in a focal stroke model. Emerging evidence has consistently demonstrated that molecular hydrogen is a promising therapeutic option for a variety of diseases and the underlying comprehensive mechanisms is beyond pure hydroxyl radicals scavenging. The non-toxicity at high concentrations and rapid cellular diffusion features of molecular hydrogen ensure the feasibility and readiness of its clinical translation to human patients. PMID:28217294

  14. Urine concentrating and diluting ability during aging.

    PubMed

    Sands, Jeff M

    2012-12-01

    Urine concentrating ability is reduced during normal aging in people and rats. The abundance of many of the key transport proteins that contribute to urine concentrating ability is reduced in the kidney medulla of aged rats. The reductions in water, sodium, and urea transport protein abundances, and their reduced response to water restriction, contribute to the reduced ability of aged rats to concentrate their urine and conserve water. If similar mechanisms occur in human kidneys, it would provide a molecular explanation for the reduced urine concentrating ability in aging and may provide opportunities for novel therapeutic approaches to improve urine concentrating ability and/or nocturnal polyuria.

  15. Historical review: Cytokines as therapeutics and targets of therapeutics.

    PubMed

    Vilcek, Jan; Feldmann, Marc

    2004-04-01

    Cytokine research has spawned the introduction of new therapies that have revolutionized the treatment of many important diseases. These therapeutic advances have resulted from two very different strategies. The first therapeutic strategy embodies the administration of purified, recombinant cytokines. The second relies on the administration of therapeutics that inhibit the harmful effects of upregulated, endogenous cytokines. Examples of successful cytokine therapeutics include hematopoietic growth factors (colony stimulating factors) and interferons. Prime examples of cytokine antagonists that have profoundly altered the treatment of some inflammatory disorders are agents that inhibit the effects of tumor necrosis factor (TNF). In this article, we highlight some of the studies that have been responsible for the introduction of cytokine and anti-cytokine therapies, with emphasis on the development of interferons and anti-TNF agents.

  16. Nucleic acids as therapeutic agents.

    PubMed

    Alvarez-Salas, Luis M

    2008-01-01

    Therapeutic nucleic acids (TNAs) and its precursors are applied to treat several pathologies and infections. TNA-based therapy has different rationales and mechanisms and can be classified into three main groups: 1) Therapeutic nucleotides and nucleosides; 2) Therapeutic oligonucleotides; and 3) Therapeutic polynucleotides. This review will focus in those TNAs that have reached clinical trials with anticancer and antiviral protocols, the two most common applications of TNAs. Although therapeutic nucleotides and nucleosides that interfere with nucleic acid metabolism and DNA polymerization have been successfully used as anticancer and antiviral drugs, they often produce toxic secondary effects related to dosage and continuous use. The use of oligonucleotides such as ribozyme and antisense oligodeoxynucleotides (AS-ODNs) showed promise as therapeutic moieties but faced several issues such as nuclease sensitivity, off-target effects and efficient delivery. Nevertheless, immunostimulatory oligodeoxynucleotides and AS-ODNs represent the most successful group of therapeutic oligonucleotides in the clinic. A newer group of therapeutic oligonucleotides, the aptamers, is rapidly advancing towards early detection and treatment alternatives the have reached the commercial interest. Despite the very high in vitro efficiency of small interfering RNAs (siRNAs) they present issues with intracellular target accessibility, specificity and delivery. DNA vaccines showed great promise, but they resulted in very poor responses in the clinic and further development is uncertain. Despite their many issues, the exquisite specificity and versatility of therapeutic oligonucleotides attracts a great deal of research and resources that will certainly convert them in the TNA of choice for treating cancer and viral diseases in the near future.

  17. The Mechanics of Human Achievement.

    PubMed

    Duckworth, Angela L; Eichstaedt, Johannes C; Ungar, Lyle H

    2015-07-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers.

  18. The Mechanics of Human Achievement

    PubMed Central

    Duckworth, Angela L.; Eichstaedt, Johannes C.; Ungar, Lyle H.

    2015-01-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers. PMID:26236393

  19. [Therapeutic management of neurodermatitis atopica].

    PubMed

    Kägi, M K

    1998-08-01

    The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.

  20. Optical assessment of nonimaging concentrators.

    PubMed

    Timinger, A; Kribus, A; Ries, H; Smith, T; Walther, M

    2000-11-01

    An optical measurement method for nonimaging radiation concentrators is proposed. A Lambertian light source is placed in the exit aperture of the concentrator. Looking into the concentrator's entrance aperture from a remote position, one can photograph the transmission patterns. The patterns show the transmission of radiation through the concentrator with the full resolution of the four-dimensional phase space of geometric optics. By matching ray-tracing simulations to the measurement, one can achieve detailed and accurate information about the geometry of the concentrator. This is a remote, noncontact measurement and can be performed in situ for installed concentrators. Additional information regarding small-scale reflector waviness and surface reflectivity can also be obtained from the same measurement with additional analysis.

  1. Engineered Hybrid Nanoparticles for On-Demand Diagnostics and Therapeutics.

    PubMed

    Nguyen, Kim Truc; Zhao, Yanli

    2015-12-15

    Together with the simultaneous development of nanomaterials and molecular biology, the bionano interface brings about various applications of hybrid nanoparticles in nanomedicine. The hybrid nanoparticles not only present properties of the individual components but also show synergistic effects for specialized applications. Thus, the development of advanced hybrid nanoparticles for targeted and on-demand diagnostics and therapeutics of diseases has rapidly become a hot research topic in nanomedicine. The research focus is to fabricate novel classes of programmable hybrid nanoparticles that are precisely engineered to maximize drug concentrations in diseased cells, leading to enhanced efficacy and reduced side effects of chemotherapy for the disease treatment. In particular, the hybrid nanoparticle platforms can simultaneously target diseased cells, enable the location to be imaged by optical methods, and release therapeutic drugs to the diseased cells by command. This Account specially discusses the rational fabrication of integrated hybrid nanoparticles and their applications in diagnostics and therapeutics. For diagnostics applications, hybrid nanoparticles can be utilized as imaging agents that enable detailed visualization at the molecular level. By the use of suitable targeting ligands incorporated on the nanoparticles, targeted optical imaging may be feasible with improved performance. Novel imaging techniques such as multiphoton excitation and photoacoustic imaging using near-infrared light have been developed using the intrinsic properties of particular nanoparticles. The use of longer-wavelength excitation sources allows deeper penetration into the human body for disease diagnostics and at the same time reduces the adverse effects on normal tissues. Furthermore, multimodal imaging techniques have been achieved by combining several types of components in nanoparticles, offering higher accuracy and better spatial views, with the aim of detecting life

  2. Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation

    PubMed Central

    Huo, Zhi-Jun; Wang, Shi-Jiang; Wang, Zhi-Qi; Zuo, Wen-Shu; Liu, Ping; Pang, Bo; Liu, Kai

    2015-01-01

    The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA–TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers. PMID:26177628

  3. Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

    PubMed

    Huo, Zhi-Jun; Wang, Shi-Jiang; Wang, Zhi-Qi; Zuo, Wen-Shu; Liu, Ping; Pang, Bo; Liu, Kai

    2015-10-01

    The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.

  4. How to Use Equipment Therapeutically.

    ERIC Educational Resources Information Center

    Bowne, Douglas

    1986-01-01

    Shares therapeutic and economic practices surrounding equipment used in New York's Higher Horizons adventure program of therapy for troubled youth. Encourages educators, therapists, and administrators to explore relationship between equipment selection, program goals, and clients. (NEC)

  5. Mesenchymal Stem Cells as Therapeutics

    PubMed Central

    Parekkadan, Biju; Milwid, Jack M.

    2013-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID:20415588

  6. Therapeutic Recreation and Adult Education.

    ERIC Educational Resources Information Center

    Jones, David

    1993-01-01

    Therapeutic recreation is a means of empowering individuals with disabilities through arts or sports. The field has developed differently in the United States and the United Kingdom; the former emphasizes professionalization and the latter the right to adult education. (SK)

  7. Inhalation delivery of protein therapeutics.

    PubMed

    Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

    2013-04-01

    Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

  8. RNAi therapeutics for CNS disorders.

    PubMed

    Boudreau, Ryan L; Davidson, Beverly L

    2010-06-18

    RNA interference (RNAi) is a process of sequence-specific gene silencing and serves as a powerful molecular tool to manipulate gene expression in vitro and in vivo. RNAi technologies have been applied to study gene function and validate drug targets. Researchers are investigating RNAi-based compounds as novel therapeutics to treat a variety of human diseases that are currently lacking sufficient treatment. To date, numerous studies support that RNAi therapeutics can improve disease phenotypes in various rodent models of human disease. Here, we focus on the development of RNAi-based therapies aimed at treating neurological disorders for which reduction of mutant or toxic gene expression may provide clinical benefit. We review RNAi-based gene-silencing strategies, proof-of-concept studies testing therapeutic RNAi for CNS disorders, and highlight the most recent research aimed at transitioning RNAi-based therapeutics toward clinical trials.

  9. Targeted Strategies for Henipavirus Therapeutics

    PubMed Central

    Bossart, Katharine N; Bingham, John; Middleton, Deborah

    2007-01-01

    Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds. PMID:19440455

  10. Substoichiometric inhibition of transthyretin misfolding by immune-targeting sparsely populated misfolding intermediates: a potential diagnostic and therapeutic for TTR amyloidoses

    PubMed Central

    Galant, Natalie J.; Bugyei-Twum, Antoinette; Rakhit, Rishi; Walsh, Patrick; Sharpe, Simon; Arslan, Pharhad Eli; Westermark, Per; Higaki, Jeffrey N.; Torres, Ronald; Tapia, José; Chakrabartty, Avijit

    2016-01-01

    Wild-type and mutant transthyretin (TTR) can misfold and deposit in the heart, peripheral nerves, and other sites causing amyloid disease. Pharmacological chaperones, Tafamidis® and diflunisal, inhibit TTR misfolding by stabilizing native tetrameric TTR; however, their minimal effective concentration is in the micromolar range. By immune-targeting sparsely populated TTR misfolding intermediates (i.e. monomers), we achieved fibril inhibition at substoichiometric concentrations. We developed an antibody (misTTR) that targets TTR residues 89–97, an epitope buried in the tetramer but exposed in the monomer. Nanomolar misTTR inhibits fibrillogenesis of misfolded TTR under micromolar concentrations. Pan-specific TTR antibodies do not possess such fibril inhibiting properties. We show that selective targeting of misfolding intermediates is an alternative to native state stabilization and requires substoichiometric concentrations. MisTTR or its derivative may have both diagnostic and therapeutic potential. PMID:27122057

  11. Therapeutic Vaccines for Chronic Infections

    NASA Astrophysics Data System (ADS)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  12. Elevated Vancomycin Trough Concentration: Increased Efficacy and/or Toxicity?

    PubMed Central

    Elyasi, Sepideh; Khalili, Hossein; Dashti-Khavidaki, Simin; Emadi-Koochak, Hamid; Mohammadpour, Amirhooshang; Abdollahi, Alireza

    2014-01-01

    Vancomycin susceptibility of methicillin-resistant Staphylococcus aureus has been changed over time and its average minimum inhibitory concentration increased from 1.5 to 1.75 mg/L.A recently published guideline by the American Society of Health Pharmacist recommended a daily dose of 15-20 mg/Kg every 8 to 12 hours of vancomycin to achieve a trough concentration between 15-20 mg/L for treatment of severe infections. Medical records of 69 patients from infectious ward of Imam Khomeini hospital, with suspected or confirmed gram-positive infection who had at least one trough level of vancomycin, were evaluated regarding vancomycin therapeutic goal; efficacy and renal safety. Most of patients (60.6%) with severe infections did not achieve the recommended vancomycin trough level during treatment course. Time to normalization of the signs and symptoms of infection did not correlate with the patients’ serum vancomycin trough levels. At the end of treatment course, there was no significant correlation between patients’ creatinine clearance and vancomycin trough levels (P=0.32). However, patients’cratinine clearance showed a negatively significant correlation with trough level of vancomycin (P=0.01). Vancomycin induced nephrotoxicity was detected in 4.3% of the patients. These data showed that vancomycin trough level may not necessarily assure treatment success, and also it would not essentially predict the risk of vancomycin induced nephrotoxicity. However, more well designed studies with larger sample size needed for better clinical and practical judgment. PMID:25587313

  13. EDUCATIONAL ACHIEVEMENT AND THE NAVAJO.

    ERIC Educational Resources Information Center

    HAAS, JOHN; MELVILLE, ROBERT

    A STUDY WAS DEVISED TO APPRAISE THE ACADEMIC ACHIEVEMENT OF NAVAJO STUDENTS LIVING IN DORMITORIES AWAY FROM THE INDIAN RESERVATION. THE FOLLOWING SEVEN FACTORS WERE CHOSEN TO BE INVESTIGATED AS BEING DIRECTLY RELATED TO ACHIEVEMENT--(1) INTELLIGENCE, (2) READING ABILITY, (3) ANXIETY, (4) SELF-CONCEPT, (5) MOTIVATION, (6) VERBAL DEVELOPMENT, (7)…

  14. Sociocultural Origins of Achievement Motivation

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    1977-01-01

    Presents a theoretical review of work on sociocultural influences on achievement, focusing on a critical evaluation of the work of David McClellan. Offers an alternative conception of achievement motivation which stresses the role of contextual and situational factors in addition to personality factors. Available from: Transaction Periodicals…

  15. Raising Boys' Achievement in Schools.

    ERIC Educational Resources Information Center

    Bleach, Kevan, Ed.

    This book offers insights into the range of strategies and good practice being used to raise the achievement of boys. Case studies by school-based practitioners suggest ideas and measures to address the issue of achievement by boys. The contributions are: (1) "Why the Likely Lads Lag Behind" (Kevan Bleach); (2) "Helping Boys Do…

  16. Teaching the Low Level Achiever.

    ERIC Educational Resources Information Center

    Salomone, Ronald E., Ed.

    1986-01-01

    Intended for teachers of the English language arts, the articles in this issue offer suggestions and techniques for teaching the low level achiever. Titles and authors of the articles are as follows: (1) "A Point to Ponder" (Rachel Martin); (2) "Tracking: A Self-Fulfilling Prophecy of Failure for the Low Level Achiever" (James Christopher Davis);…

  17. Early Intervention and Student Achievement

    ERIC Educational Resources Information Center

    Hormes, Mridula T.

    2009-01-01

    The United States Department of Education has been rigorous in holding all states accountable with regard to student achievement. The No Child Left Behind Act of 2001 clearly laid out federal mandates for all schools to follow. K-12 leaders of public schools are very aware of the fact that results in terms of student achievement need to improve…

  18. Parental Involvement and Academic Achievement

    ERIC Educational Resources Information Center

    Goodwin, Sarah Christine

    2015-01-01

    This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

  19. Asperger Syndrome and Academic Achievement.

    ERIC Educational Resources Information Center

    Griswold, Deborah E.; Barnhill, Gena P.; Myles, Brenda Smith; Hagiwara, Taku; Simpson, Richard L.

    2002-01-01

    A study focused on identifying the academic characteristics of 21 children and youth who have Asperger syndrome. Students had an extraordinary range of academic achievement scores, extending from significantly above average to far below grade level. Lowest achievement scores were shown for numerical operations, listening comprehension, and written…

  20. Perils of Standardized Achievement Testing

    ERIC Educational Resources Information Center

    Haladyna, Thomas M.

    2006-01-01

    This article argues that the validity of standardized achievement test-score interpretation and use is problematic; consequently, confidence and trust in such test scores may often be unwarranted. The problem is particularly severe in high-stakes situations. This essay provides a context for understanding standardized achievement testing, then…

  1. Stress Correlates and Academic Achievement.

    ERIC Educational Resources Information Center

    Bentley, Donna Anderson; And Others

    An ongoing concern for educators is the identification of factors that contribute to or are associated with academic achievement; one such group of variables that has received little attention are those involving stress. The relationship between perceived sources of stress and academic achievement was examined to determine if reactions to stress…

  2. School Size and Student Achievement

    ERIC Educational Resources Information Center

    Riggen, Vicki

    2013-01-01

    This study examined whether a relationship between high school size and student achievement exists in Illinois public high schools in reading and math, as measured by the Prairie State Achievement Exam (PSAE), which is administered to all Illinois 11th-grade students. This study also examined whether the factors of socioeconomic status, English…

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

    PubMed Central

    Krasowski, Matthew D.

    2010-01-01

    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. PMID:20640233

  4. Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part II. Pathophysiological and therapeutic aspects

    PubMed Central

    Módis, Katalin; Bos, Eelke M; Calzia, Enrico; van Goor, Harry; Coletta, Ciro; Papapetropoulos, Andreas; Hellmich, Mark R; Radermacher, Peter; Bouillaud, Frédéric; Szabo, Csaba

    2014-01-01

    Emerging work demonstrates the dual regulation of mitochondrial function by hydrogen sulfide (H2S), including, at lower concentrations, a stimulatory effect as an electron donor, and, at higher concentrations, an inhibitory effect on cytochrome C oxidase. In the current article, we overview the pathophysiological and therapeutic aspects of these processes. During cellular hypoxia/acidosis, the inhibitory effect of H2S on complex IV is enhanced, which may shift the balance of H2S from protective to deleterious. Several pathophysiological conditions are associated with an overproduction of H2S (e.g. sepsis), while in other disease states H2S levels and H2S bioavailability are reduced and its therapeutic replacement is warranted (e.g. diabetic vascular complications). Moreover, recent studies demonstrate that colorectal cancer cells up-regulate the H2S-producing enzyme cystathionine β-synthase (CBS), and utilize its product, H2S, as a metabolic fuel and tumour-cell survival factor; pharmacological CBS inhibition or genetic CBS silencing suppresses cancer cell bioenergetics and suppresses cell proliferation and cell chemotaxis. In the last chapter of the current article, we overview the field of H2S-induced therapeutic ‘suspended animation’, a concept in which a temporary pharmacological reduction in cell metabolism is achieved, producing a decreased oxygen demand for the experimental therapy of critical illness and/or organ transplantation. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:23991749

  5. Scattering Solar Thermal Concentrators

    SciTech Connect

    Giebink, Noel C.

    2015-01-31

    This program set out to explore a scattering-based approach to concentrate sunlight with the aim of improving collector field reliability and of eliminating wind loading and gross mechanical movement through the use of a stationary collection optic. The approach is based on scattering sunlight from the focal point of a fixed collection optic into the confined modes of a sliding planar waveguide, where it is transported to stationary tubular heat transfer elements located at the edges. Optical design for the first stage of solar concentration, which entails focusing sunlight within a plane over a wide range of incidence angles (>120 degree full field of view) at fixed tilt, led to the development of a new, folded-path collection optic that dramatically out-performs the current state-of-the-art in scattering concentration. Rigorous optical simulation and experimental testing of this collection optic have validated its performance. In the course of this work, we also identified an opportunity for concentrating photovoltaics involving the use of high efficiency microcells made in collaboration with partners at the University of Illinois. This opportunity exploited the same collection optic design as used for the scattering solar thermal concentrator and was therefore pursued in parallel. This system was experimentally demonstrated to achieve >200x optical concentration with >70% optical efficiency over a full day by tracking with <1 cm of lateral movement at fixed latitude tilt. The entire scattering concentrator waveguide optical system has been simulated, tested, and assembled at small scale to verify ray tracing models. These models were subsequently used to predict the full system optical performance at larger, deployment scale ranging up to >1 meter aperture width. Simulations at an aperture widths less than approximately 0.5 m with geometric gains ~100x predict an overall optical efficiency in the range 60-70% for angles up to 50 degrees from normal. However, the

  6. Emerging therapeutic approaches for the management of diabetes mellitus and macrovascular complications.

    PubMed

    Golden, Sherita Hill

    2011-08-02

    Type 2 diabetes mellitus (DM) affects an estimated 25.8 million people in the United States and is the 7th leading cause of death. While effective therapy can prevent or delay the complications that are associated with diabetes, according to the Center for Disease Control, 35% of Americans with DM are undiagnosed, and another 79 million Americans have blood glucose levels that greatly increase their risk of developing DM in the next several years. One of the Healthy People 2020 goals is to reduce the disease and economic burden of DM and improve the quality of life for all persons who have, or are at risk for, DM. Achieving this goal requires a concentrated focus on improving the management of diabetes and in targeting prevention of macrovascular complications. This article reviews established and emerging therapeutic approaches for managing DM and prevention of macrovascular complications.

  7. Recent advances in metamaterial split-ring-resonator circuits as biosensors and therapeutic agents.

    PubMed

    RoyChoudhury, Sohini; Rawat, Vaishali; Jalal, Ahmed Hasnain; Kale, S N; Bhansali, Shekhar

    2016-12-15

    Potential applications of thin film metamaterials are diverse and their realization to offer miniaturized waveguides, antennas and shielding patterns are on anvil. These artificially engineered structures can produce astonishing electromagnetic responses because of their constituents being engineered at much smaller dimensions than the wavelength of the incident electromagnetic wave, hence behaving as artificial materials. Such micro-nano dimensions of thin film metamaterial structures can be customized for various applications due to their exclusive responses to not only electromagnetic, but also to acoustic and thermal waves that surpass the natural materials' properties. In this paper, the recent major advancements in the emerging fields of diagnostics (sensors) and therapeutics involving thin film metamaterials have been reviewed and underlined; discussing their edge over conventional counterpart techniques; concentrating on their design considerations and feasible ways of achieving them. Challenges faced in sensitivity, precision, accuracy and factors that interfere with the degree of performance of the sensors are also dealt with, herein.

  8. Iatrogenic hyperadrenocorticism in a cat following a short therapeutic course of methylprednisolone acetate.

    PubMed

    Ferasin, L

    2001-06-01

    Iatrogenic hyperadrenocorticism (or iatrogenic Cushing's syndrome) is an adrenal disorder that may result from long-term administration of glucocorticoids for therapeutic purposes, most often given to treat allergic or immune-mediated disorders. Prolonged treatment with synthetic glucocorticoids can suppress hypothalamic corticotrophin releasing hormone and plasma adrenocorticotrophic hormone (ACTH), thus causing a functional inactivity of the adrenal cortex. The result is a clinical syndrome of hyperadrenocorticism but with basal and ACTH-stimulated plasma cortisol concentrations that are consistent with spontaneous hypoadrenocorticism (Addison's disease). Whilst iatrogenic hyperadrenocorticism is relatively frequent in dogs, the diagnosis of iatrogenic hyperadrenocorticism in cats is very uncommon because this species has been found to be remarkably resistant to prolonged administration of glucocorticoids. To the author's knowledge, there are only two published clinical cases of feline iatrogenic Cushing's syndrome. This report describes a case of iatrogenic hyperadrenocorticism in a cat, and shows how normalisation of the adrenal function was achieved with supportive treatment and withdrawal of glucocorticoid administration.

  9. Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

    NASA Astrophysics Data System (ADS)

    Chen, Kuan-Ju

    Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

  10. [Evidence-based therapeutic drug monitoring of lopinavir].

    PubMed

    Barrail-Tran, Aurélie; Taburet, Anne-Marie; Poirier, Jean-Marie

    2011-01-01

    The HIV protease inhibitor lopinavir presents a wide inter-individual variability related to liver and intestinal metabolism involving CYP3A. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of lopinavir could improve patient care. In naïve or pretreated HIV-infected patients, no relationship could be evidenced between virological efficacy and trough lopinavir concentration, most likely because concentrations are above inhibitory concentrations. Although data are limited, patients with elevated triglycerides and cholesterol had trough lopinavir concentrations >8 000 ng/mL. These data suggest that the level of evidence of interest of lopinavir therapeutic drug monitoring is may be recommended in some situations such as children, pregnant women, pretreated patients if the number of mutations is <5, when coadministration with drug with metabolizing enzyme inducing properties is warranted and toxicity.

  11. What is a Therapeutic HIV Vaccine?

    MedlinePlus

    ... Services HIV Overview What is a Therapeutic HIV Vaccine? (Last updated 10/17/2016; last reviewed 10/ ... from the body. What is a therapeutic HIV vaccine? A therapeutic HIV vaccine is a vaccine that’s ...

  12. Myeloid-derived suppressor cells: therapeutic modulation in cancer.

    PubMed

    Wilcox, Ryan A

    2012-01-01

    Improved understanding of the cellular and molecular basis of adaptive immunity has been realized over the past few decades, leading to the development of novel immunotherapeutic strategies capable of promoting host anti-tumor immunity. In order to achieve clinically meaningful results, further understanding of the mechanisms by which tumors suppress host immunity, and the development of therapeutic strategies which overcome tumor-associated immune suppression, will be necessary. Myeloid-derived cells with potent immunosuppressive properties are ubiquitous in human cancers. Improved mechanistic understanding of factors promoting their development, activation and mechanisms of immune suppression are being translated into novel therapeutic approaches, and will be summarized herein.

  13. Green synthesis of therapeutic nanoparticles: an expanding horizon.

    PubMed

    Kumar, Sandeep; Lather, Viney; Pandita, Deepti

    2015-01-01

    Nanotechnology continues to achieve tremendous awards in therapeutics, but the economical and ecofriendly production of nanoparticles (NPs) is still in infancy, simply due to the nanotoxicity, unprecedented health hazards and scale up issues. Green nanotechnology was introduced in the quest to mitigate such risks by utilizing natural resources as biological tool for NP synthesis. The key advantages offered by green approach include lower capital and operating expenses, reduced environmental impacts, superior biocompatibility and higher stability. In this review, we shed light on the biosynthesis of therapeutic NPs along with their numerous biomedical applications. Toxicity aspects of NPs and the impact of green approach on it, is also discussed briefly.

  14. Childhood Obesity and Cognitive Achievement.

    PubMed

    Black, Nicole; Johnston, David W; Peeters, Anna

    2015-09-01

    Obese children tend to perform worse academically than normal-weight children. If poor cognitive achievement is truly a consequence of childhood obesity, this relationship has significant policy implications. Therefore, an important question is to what extent can this correlation be explained by other factors that jointly determine obesity and cognitive achievement in childhood? To answer this question, we exploit a rich longitudinal dataset of Australian children, which is linked to national assessments in math and literacy. Using a range of estimators, we find that obesity and body mass index are negatively related to cognitive achievement for boys but not girls. This effect cannot be explained by sociodemographic factors, past cognitive achievement or unobserved time-invariant characteristics and is robust to different measures of adiposity. Given the enormous importance of early human capital development for future well-being and prosperity, this negative effect for boys is concerning and warrants further investigation.

  15. Using Design To Achieve Sustainability

    EPA Science Inventory

    Sustainability is defined as meeting the needs of this generation without compromising the ability of future generations to meet their needs. This is a conditional statement that places the responsibility for achieving sustainability squarely in hands of designers and planners....

  16. Achieving Efficiencies in Army Installations.

    DTIC Science & Technology

    2007-11-02

    34" ’■■"■" 1 USAWC STRATEGY RESEARCH PROJECT Achieving Efficiencies in Army Installations by Richard Fliss Col. Richard M. Meinhart Project...government agency. STRATEGY RESEARCH PROJECT ACHIEVING EFFICIENCIES IN ARMY INSTALLATIONS BY RICHARD FLISS DISTRIBUTION STATEMENT A: Approved...for public release. Distribution is unlimited. DTIC QUALITY INSPECTED & USAWC CLASS OF 1998 U.S. ARMY WAR COLLEGE, CARLISLE BARRACKS, PA 17013-5050

  17. [Therapeutic monitoring of vancomycin in routine clinical practice].

    PubMed

    Kacířová, Ivana; Grundmann, Milan

    2014-10-01

    Therapeutic drug monitoring (TDM) is specific method of clinical pharmacology for monitoring of the therapy using measurement of drug serum concentrations followed interpretation and good cooperation with clinician. TDM help clinicians to quickly optimize vancomycin dosing regimens to maximize the clinical effect and minimize the toxicity of the drugs. Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance, neverthelles trough concentrations > 20 mg/L are not recommended because of the risk of nephrotoxicity. For serious infections vancomycin trough concentrations of 15-20 mg/L are recommended and for a pathogen with an MIC of 1 mg/L, the minimum trough concentration would have to be at least 15 mg/L to generate the target AUC24/MIC 400 (area under the curve/minimal inhibitory concentration). In non-complicated infections trough concentrations of 10-15 mg/L should be sufficient. For continuous infusions of vancomycin target steady-state concentration values of 15-25 mg/L have been advocated for critically ill patients.Key words: therapeutic monitoring - trough concentration - vancomycin.

  18. Silk constructs for delivery of muskuloskeletal therapeutics

    PubMed Central

    Meinel, Lorenz; Kaplan, David L.

    2012-01-01

    Silk fibroin (SF) is a biopolymer with distinguishing features from many other bio- as well as synthetic polymers. From a biomechanical and drug delivery perspective, SF combines remarkable versatility for scaffolding (solid implants, hydrogels, threads, solutions), with advanced mechanical properties and good stabilization and controlled delivery of entrapped protein and small molecule drugs, respectively. It is this combination of mechanical and pharmaceutical features which render SF so exciting for biomedical applications. his pattern along with the versatility of this biopolymer have been translated into progress for musculoskeletal applications. We review the use and potential of silk fibroin for systemic and localized delivery of therapeutics in diseases affecting the musculoskeletal system. We also present future directions for this biopolymer as well as the necessary research and development steps for their achievement. PMID:22522139

  19. Controlling subcellular delivery to optimize therapeutic effect

    PubMed Central

    Mossalam, Mohanad; Dixon, Andrew S; Lim, Carol S

    2010-01-01

    This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy. PMID:21113240

  20. Converting Human Proteins into Precision Polymer Therapeutics.

    PubMed

    Boldt, Felix; Liu, Weina; Wu, Yuzhou; Weil, Tanja

    2016-01-01

    Cells as the smallest unit of life rely on precise macromolecules and programmable supramolecular interactions to accomplish the various vital functions. To translate such strategies to precisely control architectures and interactions into the synthetic world represents an exciting endeavor. Polymers with distinct structures, sequences and architectures are still challenging to achieve. However, in particular for biomedical applications, reproducible synthesis, narrow dispersities, tunable functionalities and additionally biocompatibility of the polymeric materials are crucial. Polymers derived from protein precursors provide many advantages of proteins such as precise monomer sequences and contour lengths, biodegradability and multiple functionalities, which can be synergistically combined with the valuable features of synthetic polymers e.g. stability, tunable solubility and molecular weights. The resulting polymeric biohybrid materials offer many applications ranging from drug delivery to biosensing and therapeutic hydrogels. This minireview summarizes the most recent advances in this field.

  1. Hydrogels for central nervous system therapeutic strategies.

    PubMed

    Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

    2015-12-01

    The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described.

  2. Protein prenylation: enzymes, therapeutics, and biotechnology applications.

    PubMed

    Palsuledesai, Charuta C; Distefano, Mark D

    2015-01-16

    Protein prenylation is a ubiquitous covalent post-translational modification found in all eukaryotic cells, comprising attachment of either a farnesyl or a geranylgeranyl isoprenoid. It is essential for the proper cellular activity of numerous proteins, including Ras family GTPases and heterotrimeric G-proteins. Inhibition of prenylation has been extensively investigated to suppress the activity of oncogenic Ras proteins to achieve antitumor activity. Here, we review the biochemistry of the prenyltransferase enzymes and numerous isoprenoid analogs synthesized to investigate various aspects of prenylation and prenyltransferases. We also give an account of the current status of prenyltransferase inhibitors as potential therapeutics against several diseases including cancers, progeria, aging, parasitic diseases, and bacterial and viral infections. Finally, we discuss recent progress in utilizing protein prenylation for site-specific protein labeling for various biotechnology applications.

  3. Mechanisms and therapeutic effectiveness of lactobacilli

    PubMed Central

    Di Cerbo, Alessandro; Palmieri, Beniamino; Aponte, Maria; Morales-Medina, Julio Cesar; Iannitti, Tommaso

    2016-01-01

    The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword ‘Lactobacillus’. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects. PMID:26578541

  4. Targeted intracellular delivery of therapeutics: an overview.

    PubMed

    Rawat, A; Vaidya, B; Khatri, K; Goyal, A K; Gupta, P N; Mahor, S; Paliwal, R; Rai, S; Vyas, S P

    2007-09-01

    During the last decade, intracellular drug delivery has become an emerging area of research in the medical and pharmaceutical field. Many therapeutic agents such as drugs and DNA/oligonucleotides can be delivered not just to the cell but also to a particular compartment of that cell to achieve better activity e.g. proapoptotic drugs to the mitochondria, antibiotics and enzymes to the lysosomes and various anticancer drugs and gene to the nucleus. The lipidic nature of biological membrans is the major obstacle to the intracellular delivery of macromolecular and ionic drugs. Additionally, after endocytosis, the lysosome, the major degradation compartment, needs to be avoided for better activity. To avoid these problems, various carriers have been investigated for efficient intracellular delivery, either by direct entry to cytoplasm or by escaping the endosomal compartment. These include cell penetrating peptides, and carrier systems such as liposomes, cationic lipids and polymers, polymeric nanoparticles, etc. Various properties of these carriers, including size, surface charge, composition and the presence of cell specific ligands, alter their efficacy and specificity towards particular cells. This review summarizes various aspects of targeted intracellular delivery of therapeutics including pathways, mechanisms and approaches. Various carrier constructs having potential for targeted intracellular delivery are also been discussed.

  5. PERIORAL DERMATITIS: STILL A THERAPEUTIC CHALLENGE.

    PubMed

    Mokos, Zrinka Bukvić; Kummer, Ana; Mosler, Elvira Lazić; Čeović, Romana; Basta-Juzbašić, Aleksandra

    2015-06-01

    Perioral dermatitis is a common and often chronic dermatosis. In its classic form, it primarily affects women aged 15 to 45 years, but there are also variants including lupus-like and granulomatous perioral dermatitis, where granulomatous form is more common in childhood and affects mostly prepubescent boys. The etiopathogenesis of the disease remains unclear, but there is a frequent finding of prolonged use of topical products, especially corticosteroids, in the treatment of rosacea and seborrheic dermatitis, preceding the clinical manifestation of perioral dermatitis. Other causes important for the occurrence of the disease include various skin irritants, as well as other physical and hormonal factors, which all share the epidermal barrier dysfunction as an underlying main pathogenic factor. Clinical presentation of papulovesicular eruption in the perioral region with a typical narrow spared zone around the edge of the lips is characteristic. Therapeutic approach should be individually addressed, depending on the severity of clinical presentation and patient's age, with special attention to patient's education and continuous psychological support. In mild forms of perioral dermatitis, 'zero therapy' is the treatment of choice. In the initial treatment period, patients with steroid-induced perioral dermatitis should be closely followed up because the rebound phenomenon usually develops after cessation of previous topical treatment. In moderate disease, treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas in more severe cases the best validated choice is oral tetracycline in a subantimicrobial dose until complete remission is achieved. Systemic isotretinoin should be considered as a therapeutic option for patients refractory to all standard therapies.

  6. Achieving real-time performance in FIESTA

    NASA Technical Reports Server (NTRS)

    Wilkinson, William; Happell, Nadine; Miksell, Steve; Quillin, Robert; Carlisle, Candace

    1988-01-01

    The Fault Isolation Expert System for TDRSS Applications (FIESTA) is targeted for operation in a real-time online environment. Initial stages of the prototype development concentrated on acquisition and representation of the knowledge necessary to isolate faults in the TDRSS Network. Recent efforts focused on achieving real-time performance including: a discussion of the meaning of FIESTA real-time requirements, determination of performance levels (benchmarking) and techniques for optimization. Optimization techniques presented include redesign of critical relations, filtering of redundant data and optimization of patterns used in rules. Results are summarized.

  7. Emerging therapeutics for Alzheimer's disease.

    PubMed

    Chiang, Karen; Koo, Edward H

    2014-01-01

    Despite decades of intense research, therapeutics for Alzheimer's disease (AD) are still limited to symptomatic treatments that possess only short-term efficacy. Recently, several large-scale Phase III trials targeting amyloid-β production or clearance have failed to show efficacy, leading to a reexamination of the amyloid hypothesis as well as highlighting the need to explore alternatives in both clinical testing strategies and drug discovery targets. In this review, we discuss therapeutics currently being tested in clinical trials and up-and-coming interventions that have shown promise in animal models, devoting attention to the mechanisms that may underlie their ability to influence disease progression and placing particular emphasis on tau therapeutics.

  8. Polymeric anti-HIV therapeutics.

    PubMed

    Danial, Maarten; Klok, Harm-Anton

    2015-01-01

    The scope of this review is to highlight the application of polymer therapeutics in an effort to curb the transmission and infection of the human immunodeficiency virus (HIV). Following a description of the HIV life cycle, the use of approved antiretroviral drugs that inhibit critical steps in the HIV infection process is highlighted. After that, a comprehensive overview of the structure and inhibitory properties of polymeric anti-HIV therapeutic agents is presented. This overview will include inhibitors based on polysaccharides, synthetic polymers, dendritic polymers, polymer conjugates as well as polymeric DC-SIGN antagonists. The review will conclude with a section that discusses the applications of polymers and polymer conjugates as systemic and topical anti-HIV therapeutics.

  9. Oligonucleotide conjugates for therapeutic applications

    PubMed Central

    Winkler, Johannes

    2013-01-01

    Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake machanisms and pharmacokinetic properties. PMID:23883124

  10. Therapeutic and recreational methadone cardiotoxicity.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2016-04-01

    Several classes of drugs have been associated with an increased risk of cardiovascular disease and occurrence of arrhythmias potentially involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart possibly due to methadone use. 60 cases were included in the study in total and were divided into three groups (therapeutic methadone users: 20 cases, recreational methadone users: 20 cases, and sudden death group in subjects who had never taken methadone: 20 cases). Autopsies, histology, biochemistry and toxicology were performed in all cases. Macroscopic and microscopic investigation results in therapeutic methadone users were similar to those observed in sudden, unexpected deaths in non-methadone users. In recreational methadone consumers, macroscopic and microscopic examination of the heart failed to provide results consistent with acute or chronic myocardial or coronary damage, thereby corroborating the hypothesis of death most likely following respiratory depression.

  11. Potential therapeutic applications of biosurfactants.

    PubMed

    Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

    2013-12-01

    Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications.

  12. Therapeutic cloning and reproductive liberty.

    PubMed

    Sparrow, Robert

    2009-04-01

    Concern for "reproductive liberty" suggests that decisions about embryos should normally be made by the persons who would be the genetic parents of the child that would be brought into existence if the embryo were brought to term. Therapeutic cloning would involve creating and destroying an embryo, which, if brought to term, would be the offspring of the genetic parents of the person undergoing therapy. I argue that central arguments in debates about parenthood and genetics therefore suggest that therapeutic cloning would be prima facie unethical unless it occurred with the consent of the parents of the person being cloned. Alternatively, if therapeutic cloning is thought to be legitimate, this undermines the case for some uses of reproductive cloning by implying that the genetic relation it establishes between clones and DNA donors does not carry the same moral weight as it does in cases of normal reproduction.

  13. Oligonucleotide conjugates for therapeutic applications.

    PubMed

    Winkler, Johannes

    2013-07-01

    Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake mechanisms and pharmacokinetic properties.

  14. Improving chemoradiotherapy with nanoparticle therapeutics

    PubMed Central

    Eblan, Michael Joseph; Wang, Andrew Zhuang

    2014-01-01

    Chemoradiotherapy has been a key treatment paradigm in cancer management. One of the main research objectives in cancer research has been to identify agents and strategies to improve the therapeutic index of chemoradiation. Recent development of nanoparticle (NP)-based chemotherapeutics offers a unique opportunity to improve the delivery of chemotherapy, which can in turn improve chemoradiotherapy’s efficacy while lowering toxicity. NP-based chemotherapeutics also possess several characteristics that are well suited for chemoradiotherapy. Therefore, NP chemotherapeutics hold high potential in improving the therapeutic index of chemoradiotherapy. This manuscript reviews the NP properties that are favorable for chemoradiation and the rationale to utilize nanotherapeutics in chemoradiation. This review also discusses the preclinical and clinical data on using NP therapeutics in chemoradiotherapy. PMID:25429359

  15. Two concepts of therapeutic optimism

    PubMed Central

    Jansen, Lynn A

    2011-01-01

    Researchers and ethicists have long been concerned about the expectations for direct medical benefit expressed by participants in early phase clinical trials. Early work on the issue considered the possibility that participants misunderstand the purpose of clinical research or that they are misinformed about the prospects for medical benefit from these trials. Recently, however, attention has turned to the possibility that research participants are simply expressing optimism or hope about their participation in these trials. The ethical significance of this therapeutic optimism remains unclear. This paper argues that there are two distinct phenomena that can be associated with the term ‘therapeutic optimism’—one is ethically benign and the other is potentially worrisome. Distinguishing these two phenomena is crucial for understanding the nature and ethical significance of therapeutic optimism. The failure to draw a distinction between these phenomena also helps to explain why different writers on the topic often speak past one another. PMID:21551464

  16. Therapeutic target database update 2014: a resource for targeted therapeutics.

    PubMed

    Qin, Chu; Zhang, Cheng; Zhu, Feng; Xu, Feng; Chen, Shang Ying; Zhang, Peng; Li, Ying Hong; Yang, Sheng Yong; Wei, Yu Quan; Tao, Lin; Chen, Yu Zong

    2014-01-01

    Here we describe an update of the Therapeutic Target Database (http://bidd.nus.edu.sg/group/ttd/ttd.asp) for better serving the bench-to-clinic communities and for enabling more convenient data access, processing and exchange. Extensive efforts from the research, industry, clinical, regulatory and management communities have been collectively directed at the discovery, investigation, application, monitoring and management of targeted therapeutics. Increasing efforts have been directed at the development of stratified and personalized medicines. These efforts may be facilitated by the knowledge of the efficacy targets and biomarkers of targeted therapeutics. Therefore, we added search tools for using the International Classification of Disease ICD-10-CM and ICD-9-CM codes to retrieve the target, biomarker and drug information (currently enabling the search of almost 900 targets, 1800 biomarkers and 6000 drugs related to 900 disease conditions). We added information of almost 1800 biomarkers for 300 disease conditions and 200 drug scaffolds for 700 drugs. We significantly expanded Therapeutic Target Database data contents to cover >2300 targets (388 successful and 461 clinical trial targets), 20 600 drugs (2003 approved and 3147 clinical trial drugs), 20,000 multitarget agents against almost 400 target-pairs and the activity data of 1400 agents against 300 cell lines.

  17. Electrodialysis simulation to achieve optimum current density

    NASA Technical Reports Server (NTRS)

    Herrmann, Cal C.

    1993-01-01

    Electrodialysis is used to remove salts from waste or other water streams, to yield a concentrated brine and a substatially deionized product water. During the electrodialysis process, the boundary layer adjacent to the ion selective membrane can become depleted of ions, resulting in severe pH changes sometimes accompanied by precipitation, and power losses, by a process known as water splitting. In order to optimize the applied electric current density, to achieve maximum deionization without exceeding the limiting current at any point along the path, a simulation program has been created to plot ion concentrations and fluxes, and cell current densities and voltages along the electrodialysis path. A means for tapering the current density along the path is recommended.

  18. Therapeutics for Equine Endocrine Disorders.

    PubMed

    Durham, Andy E

    2017-02-09

    Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency.

  19. [Cerebral oedema: new therapeutic ways].

    PubMed

    Quintard, H; Ichai, C

    2014-06-01

    Cerebral oedema (CO) after brain injury can occur from different ways. The vasogenic and cytotoxic oedema are usually described but osmotic and hydrostatic CO, respectively secondary to plasmatic hypotonia or increase in blood pressure, can also be encountered. Addition of these several mechanisms can worsen injuries. Consequences are major, leading quickly to death secondary to intracerebral hypertension and later to neuropsychic sequelae. So therapeutic care to control this phenomenon is essential and osmotherapy is actually the only way. A better understanding of physiopathological disorders, particularly energetic ways (lactate), aquaporine function, inflammation lead to new therapeutic hopes. The promising experimental results need now to be confirmed by clinical data.

  20. Freud, transference, and therapeutic action.

    PubMed

    Abend, Sander M

    2009-07-01

    The author traces the development of Freud's conception of the nature and significance of transference in the psychoanalytic process. He notes that from 1910 onward, Freud was convinced that the analysis of the transference is the sole factor involved in the therapeutic action of psychoanalytic treatment, despite the fact that, late in his career, he observed and described the power of reconstruction to be effective as well. The author agrees with those analysts who contend that, while the analysis of the transference is essential to proper analytic technique, it is not the only agent of therapeutic impact.

  1. Optical oxygen concentration monitor

    DOEpatents

    Kebabian, P.

    1997-07-22

    A system for measuring and monitoring the concentration of oxygen uses as a light source an argon discharge lamp, which inherently emits light with a spectral line that is close to one of oxygen`s A-band absorption lines. In a preferred embodiment, the argon line is split into sets of components of shorter and longer wavelengths by a magnetic field of approximately 2,000 Gauss that is parallel to the light propagation from the lamp. The longer wavelength components are centered on an absorption line of oxygen and thus readily absorbed, and the shorter wavelength components are moved away from that line and minimally absorbed. A polarization modulator alternately selects the set of the longer wavelength, or upshifted, components or the set of the shorter wavelength, or downshifted, components and passes the selected set to an environment of interest. After transmission over a path through that environment, the transmitted optical flux of the argon line varies as a result of the differential absorption. The system then determines the concentration of oxygen in the environment based on the changes in the transmitted optical flux between the two sets of components. In alternative embodiments modulation is achieved by selectively reversing the polarity of the magnetic field or by selectively supplying the magnetic field to either the emitting plasma of the lamp or the environment of interest. 4 figs.

  2. Optical oxygen concentration monitor

    DOEpatents

    Kebabian, Paul

    1997-01-01

    A system for measuring and monitoring the concentration of oxygen uses as a light source an argon discharge lamp, which inherently emits light with a spectral line that is close to one of oxygen's A-band absorption lines. In a preferred embodiment, the argon line is split into sets of components of shorter and longer wavelengths by a magnetic field of approximately 2000 Gauss that is parallel to the light propagation from the lamp. The longer wavelength components are centered on an absorption line of oxygen and thus readily absorbed, and the shorter wavelength components are moved away from that line and minimally absorbed. A polarization modulator alternately selects the set of the longer wavelength, or upshifted, components or the set of the shorter wavelength, or downshifted, components and passes the selected set to an environment of interest. After transmission over a path through that environment, the transmitted optical flux of the argon line varies as a result of the differential absorption. The system then determines the concentration of oxygen in the environment based on the changes in the transmitted optical flux between the two sets of components. In alternative embodiments modulation is achieved by selectively reversing the polarity of the magnetic field or by selectively supplying the magnetic field to either the emitting plasma of the lamp or the environment of interest.

  3. Benchmarking concentrating photovoltaic systems

    NASA Astrophysics Data System (ADS)

    Duerr, Fabian; Muthirayan, Buvaneshwari; Meuret, Youri; Thienpont, Hugo

    2010-08-01

    Integral to photovoltaics is the need to provide improved economic viability. To achieve this goal, photovoltaic technology has to be able to harness more light at less cost. A large variety of concentrating photovoltaic concepts has provided cause for pursuit. To obtain a detailed profitability analysis, a flexible evaluation is crucial for benchmarking the cost-performance of this variety of concentrating photovoltaic concepts. To save time and capital, a way to estimate the cost-performance of a complete solar energy system is to use computer aided modeling. In this work a benchmark tool is introduced based on a modular programming concept. The overall implementation is done in MATLAB whereas Advanced Systems Analysis Program (ASAP) is used for ray tracing calculations. This allows for a flexible and extendable structuring of all important modules, namely an advanced source modeling including time and local dependence, and an advanced optical system analysis of various optical designs to obtain an evaluation of the figure of merit. An important figure of merit: the energy yield for a given photovoltaic system at a geographical position over a specific period, can be calculated.

  4. Posaconazole Therapeutic Drug Monitoring in Pediatrics and Young Adults with Cancer

    PubMed Central

    Bernardo, Valeria A.; Cross, Shane J.; Crews, Kristine R.; Flynn, Patricia M.; Hoffman, James M.; Knapp, Katherine M.; Pauley, Jennifer L.; Molinelli, Alejandro R.; Greene, William L.

    2015-01-01

    BACKGROUND Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescent, and young adult patients with cancer. At St. Jude Children’s Research Hospital, the recommended posaconazole dose in patients less than 34 kg is 18–24 mg/kg daily given in 4 divided doses. For patients 13 years and older or those weighing 34 kg or more, the recommended dose is 800 mg daily given orally in four divided doses. OBJECTIVE This study was conducted to determine if the current posaconazole dosing guidelines achieved target posaconazole plasma concentrations of ≥ 0.7 μg/mL. METHODS We examined data from patients who received treatment-dose posaconazole with at least one posaconazole plasma concentration measurement. RESULTS Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5–23.2 years). Twenty-one patients out of 33 (63.6%) had posaconazole concentrations of ≥ 0.7 μg/mL (median 1.4 μg/mL; range 0.7–2.98 μg/mL) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg per day. Patients with concentrations < 0.7 μg/mL (median 0.4 μg/mL; range 0.025–0.69 μg/mL) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg per day; p = 0.02). Of the 12 patients with concentrations < 0.7 μg/mL, seven (58.3%) were 13 years of age or older. CONCLUSIONS The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients < 13 than those > 13 years of age. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent and young adult cancer patients with routine therapeutic drug monitoring in all patients to ensure adequate

  5. [Objectives and therapeutic strategy in type 2 diabetes mellitus].

    PubMed

    Calvo Romero, J M; Lima Rodríguez, E M

    2001-07-01

    United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated definitively that patients with type 2 diabetes mellitus (DM) benefit from intensive blood glucose control, because it diminishes the risk to develop microvascular complications. The therapeutic targets in the type 2 DM have been modified in order to reduce the risk of these complications. However, aggressive treatment may be disastrous for patients with microvascular complications and/or an increased risk of hypoglycemic unawareness, and neither it would be advised in older patients or with short life expectancy. The available drugs for treatment of type 2 DM offer many options for achieving these therapeutic targets, based on the need of the individual patient. In this job we review the targets in the metabolic control of type 2 DM and their backgrounds, and we describe briefly the therapeutic strategy recommended for reaching these targets, with special attention to the new oral antidiabetic agents (repaglinide and thiazolidinediones).

  6. The endocannabinoid system and cancer: therapeutic implication

    PubMed Central

    Guindon, Josée; Hohmann, Andrea G

    2011-01-01

    The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others). The main active ingredient of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC), produces its effects through activation of CB1 and CB2 receptors. CB1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB2 receptors are concentrated predominantly, although not exclusively, in cells of the immune system. Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the endocannabinoid system and anti-tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer. This review will focus on examining how activation of the endocannabinoid system impacts breast, prostate and bone cancers in both in vitro and in vivo systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed. Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients. Further basic research on anti-cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21410463

  7. Therapeutic Recreation Education: 1999 Survey.

    ERIC Educational Resources Information Center

    Anderson, Stephen C.; Ashton-Shaeffer, Candace; Autry, Cari E.

    2000-01-01

    Examines the current status of therapeutic recreation education, documenting changes have that occurred over 30 years. Using data from surveys conducted every 10 years beginning in 1969, the study provides information on trends in programs, faculty, students, curriculum accreditation, and professional certification in programs in the United States…

  8. Therapeutic Recreation Majors' Work Preference.

    ERIC Educational Resources Information Center

    Barber, Elizabeth H.; Magafas, Anita

    1992-01-01

    Investigates the client age/disability work preference of 76 therapeutic recreation undergraduate students at 3 universities. Results indicate a preference to work with younger clients, disability groups, and physically impaired clients. Chronically ill clients were last in work preference. Students need exposure to the benefits of working with…

  9. Novel therapeutic approaches for haemophilia.

    PubMed

    Shetty, S; Ghosh, K

    2015-03-01

    The major therapy for haemophilia is plasma derived or recombinant clotting factors which are evolving steadily to increase potency, stability and half-life. Research in the area of haemophilia therapeutics, however, is not restricted only to modifications in the recombinant products, but alternate therapeutic strategies are being developed which are in different phases of experimental and clinical trials. This chapter reviews the diverse molecular innovations which are being developed for alternate therapeutic approaches in haemophilia. The data is mainly extracted from the literature and the Conference abstracts. Some of the novel therapeutic approaches include inhibition of anticoagulant pathway factors (activated protein C, antithrombin, tissue factor pathway inhibitor) by monoclonal antibodies, peptide inhibitors, DNA or RNA aptamers, use of variant coagulation factors (factor Xa, factor Va) which are more resistant to inactivation or enzymatically more active and antibody-mediated therapy including a humanized anti-factor IXa/X bispecific antibody mimicking factor VIII. Other approaches include nonsense mutation suppression, induction of prothrombotic microparticles by P-selectin-immunoglobulin chimeras, suppression of fibrinolytic potential either by antifibrinolytics or by the use of mutant molecules of fibrinolytic inhibitors. Few products are proposed as 'stand alone' treatment for haemophilia, while a few can be used as adjuvant therapies to recombinant factors with an aim to reduce the amount of factor intake. All efforts are underway to produce an alternate, novel drug for haemophilia which will have an increased half-life, subcutaneously injectable, non-immunogenic and effective both in the presence and absence of inhibitors.

  10. Therapeutic role of dietary fibre.

    PubMed Central

    Hunt, R.; Fedorak, R.; Frohlich, J.; McLennan, C.; Pavilanis, A.

    1993-01-01

    The current status of dietary fibre and fibre supplements in health and disease is reported, and the components of dietary fibre and its respective mechanical and metabolic effects with emphasis on its therapeutic potential are reviewed. Practical management guidelines are provided to help physicians encourage patients identified as having fibre deficiency to increase dietary fibre intake to the recommended level. PMID:8388284

  11. Level 2 Therapeutic Model Site

    ERIC Educational Resources Information Center

    Spears, Brad; Sanchez, David; Bishop, Jane; Rogers, Sharon; DeJong, Judith A.

    2006-01-01

    L2, one of the original sites first funded under the Therapeutic Residential Model Initiative in 2001-2002, is operated as a peripheral dormitory This dormitory cares for 185 boys and girls in grades 1-12 who attend local public schools. L2 presented an outstanding proposal which identified gaps in services and presented a reasonable budget to…

  12. Therapy Talk: Analyzing Therapeutic Discourse

    ERIC Educational Resources Information Center

    Leahy, Margaret M.

    2004-01-01

    Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

  13. Childhood vaccination: achievements and challenges.

    PubMed

    Ndumbe, P

    1996-09-01

    As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

  14. Concentrating molecules in a simple microchannel.

    PubMed

    Jiang, Hai; Daghighi, Yasaman; Chon, Chan Hee; Li, Dongqing

    2010-07-15

    A simple method is proposed and tested to concentrate sample molecules from a dilute solution in a microchannel by electrokinetic means. The microfluidic chip has a straight microchannel connecting two wells and three electrodes. This method uses electrokinetic trapping and flow control simultaneously to concentrate a charged species of interest. A numerical model of the sample concentration process is presented in this paper. Using a fluorescent dye as the sample molecules, experimental investigation into the concentration process was performed. The 90 times of the concentration increase was achieved in 110 s. The numerical simulations of the concentrating and the subsequent dispensing processes agree well with the experimental results.

  15. Thyroid abnormalities after therapeutic external radiation

    SciTech Connect

    Hancock, S.L.; McDougall, I.R.; Constine, L.S.

    1995-03-30

    The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.

  16. [Alternative therapeutic excision of intraepithelial conjunctival carcinoma with corneal extension].

    PubMed

    Zemba, M; Stamate, Alina-Cristina; Avram, Corina Ioana; Sîrbu, Laura Nicoleta Urucu; Camburu, Raluca Lăcrămioara; Ochinciuc, Uliana; Burcea, M

    2013-01-01

    Surgical treatment for conjunctival neoplasms, with wide local excision, with or without supplemental cryotherapy to the surgical margins represents the treatment of choice for this pathology. In some cases, these neoplasms can be diffuse or multifocal, with borders that are difficult to detect clinically, such that topical therapies offer a more efficient method for treating the entire ocular surface, delivering high drug concentrations at this level, with negligible systemic side effects. Beginning from the clinical case of a patient diagnosed with conjunctival intraepithelial neoplasia, we try to present other therapeutical alternatives, although in this case the therapeutical approach was the classic one.

  17. Intrapleural 'outside-in' gene therapy: therapeutics for organs of the chest via gene transfer to the pleura.

    PubMed

    Heguy, Adriana; Crystal, Ronald G

    2005-10-01

    The pleural space is an attractive site for using viral vectors to deliver gene products to the lung parenchyma, other thoracic structures and the systemic circulation. The advantages of intrapleural gene transfer using viral vectors include: (i) easy accessibility; (ii) large surface area; (iii) ability to provide high concentrations of secreted gene products to chest structures; (iv) low risk of detrimental effects of possible vector-induced inflammation compared with intravascular delivery; and (v) because it is local, lower vector doses can be used to deliver therapeutic genes to thoracic structures than less efficient systemic routes. Examples of pleural gene transfer include the use of adenovirus vectors to treat mesothelioma by transiently expressing genes that encode toxic proteins, immunomodulatory molecules or anti-angiogenesis factors. Intrapleural delivery of adeno-associated viral vectors represents an efficient strategy to treat alpha1-antitrypsin (alpha1AT) deficiency, achieving high lung and systemic therapeutic levels of alpha1AT. Intrapleural delivery of gene transfer vectors holds promise for the treatment of diseases requiring transient, localized gene expression, as well as sustained expression of genes to correct hereditary disorders requiring localized or systemic expression of the therapeutic protein.

  18. MicroRNA Targeted Therapeutic Approach for Pancreatic Cancer

    PubMed Central

    Li, Yiwei; Sarkar, Fazlul H.

    2016-01-01

    Pancreatic cancer remains the fourth leading cause of cancer-related death in the US and is expected to be the second leading cause of cancer-related death by 2030. Therefore, it is important to better understand the molecular pathogenesis, phenotypes and features of pancreatic cancer in order to design novel molecularly targeted therapies for achieving better therapeutic outcome of patients with pancreatic cancer. Recently, the roles of microRNAs (miRNAs) in the development and progression of pancreatic cancer became a hot topic in the scientific community of pancreatic cancer research. By conducting miRNA expression profiling, the aberrant expression of miRNAs was revealed in the serum and in cancer tissues from patients with pancreatic cancer. These aberrantly expressed miRNAs are critically correlated with the disease stage, drug resistance, and survival of pancreatic cancer patients. Hence, targeting these tiny molecules, the specific miRNAs, could provide an efficient and optimal approach in the therapy of pancreatic cancer. Indeed, the pre-clinical and in vivo experiments showed that nanoparticle delivery of synthetic oligonucleotides or treatment with natural agents could be useful to modulate the expression of miRNAs and thereby inhibit pancreatic cancer growth and progression, suggesting that targeting miRNAs combined with conventional anti-cancer therapeutics could be a novel therapeutic strategy for increasing drug sensitivity and achieving better therapeutic outcome of patients diagnosed with pancreatic cancer. PMID:26929739

  19. Garlic: a review of potential therapeutic effects

    PubMed Central

    Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

    2014-01-01

    Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

  20. Washington State's Student Achievement Initiative

    ERIC Educational Resources Information Center

    Pettitt, Maureen; Prince, David

    2010-01-01

    This article describes Washington State's Student Achievement Initiative, an accountability system implemented in 2005-06 that measures students' gains in college readiness, college credits earned, and degree or certificate completion. The goal of the initiative is to increase educational attainment by focusing on the critical momentum points…

  1. Meeting a Math Achievement Crisis

    ERIC Educational Resources Information Center

    Jennings, Lenora; Likis, Lori

    2005-01-01

    An urban community spotlighted declining mathematics achievement and took some measures, in which the students' performance increased substantially. The Benjamin Banneker Charter Public School in Cambridge, Massachusetts, engaged the entire community and launched the campaign called "Math Everywhere", which changed Benjamin Banneker's…

  2. Socioeconomic Determinants of Academic Achievement

    ERIC Educational Resources Information Center

    Tomul, Ekber; Savasci, Havva Sebile

    2012-01-01

    This study aims to investigate the relationship between academic achievement and the socioeconomic characteristics of elementary school 7th grade students in Burdur. The population of the study are 7th grade students who had education at elementary schools in Burdur in the 2007-2008 academic year. Two staged sampling was chosen as suitable for the…

  3. Goal Setting to Achieve Results

    ERIC Educational Resources Information Center

    Newman, Rich

    2012-01-01

    Both districts and individual schools have a very clear set of goals and skills for their students to achieve and master. In fact, except in rare cases, districts and schools develop very detailed goals they wish to pursue. In most cases, unfortunately, only the teachers and staff at a particular school or district-level office are aware of the…

  4. School Districts and Student Achievement

    ERIC Educational Resources Information Center

    Chingos, Matthew M.; Whitehurst, Grover J.; Gallaher, Michael R.

    2015-01-01

    School districts are a focus of education reform efforts in the United States, but there is very little existing research about how important they are to student achievement. We fill this gap in the literature using 10 years of student-level, statewide data on fourth- and fifth-grade students in Florida and North Carolina. A variance decomposition…

  5. Student Achievement, 1986-87.

    ERIC Educational Resources Information Center

    Mangino, Evangelina

    This report summarizes results of student achievement in the Austin (Texas) Independent School District (AISD) on the Texas Educational Assessment of Minimum Skills (TEAMS) tests in 1986-87. Major findings indicate the following: (1) 99.4% of AISD seniors to graduate in May 1987 passed the Exit-Level TEAMS tests, with only 17 denied diplomas in…

  6. Sociocultural Variation in Literacy Achievement

    ERIC Educational Resources Information Center

    Verhoeven, Ludo

    2006-01-01

    The purpose of this study was to describe the variations in literacy achievement among native and non-native upper primary school children (grades three to six) in the Netherlands. Various measures of word decoding, reading literacy and writing skill were collected from 1091 native Dutch children, 753 children with a former Dutch colonial…

  7. Game Addiction and Academic Achievement

    ERIC Educational Resources Information Center

    Sahin, Mehmet; Gumus, Yusuf Yasin; Dincel, Sezen

    2016-01-01

    The primary aim of this study was to investigate the correlation between game addiction and academic achievement. The secondary aim was to adapt a self-report instrument to measure game addiction. Three hundred and seventy high school students participated in this study. Data were collected via an online questionnaire that included a brief…

  8. The Widening Income Achievement Gap

    ERIC Educational Resources Information Center

    Reardon, Sean F.

    2013-01-01

    Has the academic achievement gap between high-income and low-income students changed over the last few decades? If so, why? And what can schools do about it? Researcher Sean F. Reardon conducted a comprehensive analysis of research to answer these questions and came up with some striking findings. In this article, he shows that income-related…

  9. Attribution Theory in Science Achievement

    ERIC Educational Resources Information Center

    Craig, Martin

    2013-01-01

    Recent research reveals consistent lags in American students' science achievement scores. Not only are the scores lower in the United States compared to other developed nations, but even within the United States, too many students are well below science proficiency scores for their grade levels. The current research addresses this problem by…

  10. Grouping Students for Increased Achievements.

    ERIC Educational Resources Information Center

    Holloway, John H.

    2001-01-01

    Reviews results of four recent studies exploring the effects of various student-grouping schemes on academic achievement. Grouping plans included multiage classrooms, full-time ability grouping, and within-classroom grouping. Two studies investigated administrator attitudes toward student grouping. Several studies found that grouping plans…

  11. Achievement, Hedonism and the Teacher.

    ERIC Educational Resources Information Center

    Ryan, Kevin

    1991-01-01

    The problem of poor school achievement is in part because students lack work and discipline values. The article suggests moral and ethical teachings inspire students to be better scholars and people; and teacher education must prepare teachers to be moral educators by reintroducing moral education into the curriculum. (SM)

  12. School Desegregation and Black Achievement.

    ERIC Educational Resources Information Center

    Cook, Thomas; And Others

    Seven papers commissioned by the National Institute of Education in order to clarify the state of recent knowledge about the effects of school desegregation on the academic achievement of black students are contained in this report. The papers, which analyze 19 "core" empirical studies on this topic, include: (1) "What Have Black Children Gained…

  13. Institutional Climate and Minority Achievement.

    ERIC Educational Resources Information Center

    Richardson, Richard C.

    This paper discusses ways that institutions can change the higher education system and environment to accommodate more minority students. The first section, "Institutional Climate and Minority Achievement," presents an overview of the problems facing colleges and universities with respect to recruiting and retaining minority students. In the…

  14. Faculty Development: Assessing Learner Achievement.

    ERIC Educational Resources Information Center

    Frey, Barbara A.; Overfield, Karen

    This study addressed the challenges of developing a faculty professional development workshop on assessment, measurement, and evaluation of achievement in adult learners. The setting for the workshop was a system of postsecondary career colleges throughout the United States. The curriculum development model of D. Kirkpatrick (1994) was used as a…

  15. Can Judges Improve Academic Achievement?

    ERIC Educational Resources Information Center

    Greene, Jay P.; Trivitt, Julie R.

    2008-01-01

    Over the last 3 decades student achievement has remained essentially unchanged in the United States, but not for a lack of spending. Over the same period a myriad of education reforms have been suggested and per-pupil spending has more than doubled. Since the 1990s the education reform attempts have frequently included judicial decisions to revise…

  16. Achieving a sustainable service advantage.

    PubMed

    Coyne, K P

    1993-01-01

    Many managers believe that superior service should play little or no role in competitive strategy; they maintain that service innovations are inherently copiable. However, the author states that this view is too narrow. For a company to achieve a lasting service advantage, it must base a new service on a capability gap that competitors cannot or will not copy.

  17. Teacher Dispositions and Student Achievement

    ERIC Educational Resources Information Center

    Vaughn, Kathleen Adams

    2012-01-01

    In an effort to close the achievement gap between students of minority and majority populations and between students in higher and lower economic circumstances, the National Council for the Accreditation of Teacher Education (NCATE) added instruction and evaluation of teacher dispositions to its requirements for credentialing prospective teachers.…

  18. Epistemological Beliefs and Academic Achievement

    ERIC Educational Resources Information Center

    Arslantas, Halis Adnan

    2016-01-01

    This study aimed to identify the relationship between teacher candidates' epistemological beliefs and academic achievement. The participants of the study were 353 teacher candidates studying their fourth year at the Education Faculty. The Epistemological Belief Scale was used which adapted to Turkish through reliability and validity work by…

  19. Towards a new era in medicine: therapeutic genome editing.

    PubMed

    Porteus, Matthew H

    2015-12-22

    Genome editing is the process of precisely modifying the nucleotide sequence of the genome. It has provided a powerful approach to research questions but, with the development of a new set of tools, it is now possible to achieve frequencies of genome editing that are high enough to be useful therapeutically. Genome editing is being developed to treat not only monogenic diseases but also infectious diseases and diseases that have both a genetic and an environmental component.

  20. [Concept of the therapeutic community].

    PubMed

    Eichhorn, H

    1983-08-01

    The historic development of therapeutic communities is discussed, and it is shown that the term has been neither conceptualized not operationalized. Their unclear aims are considered to be utopian, and the author stresses that previous studies on such communities have been too superficial. The following problems have not hitherto received attention: 1. micro- and macrosocial relationships, 2. the role of the supervisor (authority problems), 3. norms and valuation systems, 4. discipline and sanctions, 5. the problem of roles, 6. questions of indicants and efficacy. The introduction of therapeutic communities is superfluous as a means of improving the socialist health services: it is sufficient to implement the principles of socialist democracy by means of appropriate training programmes.

  1. Therapeutic approaches for celiac disease

    PubMed Central

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  2. Phosphoroorganic Metal Complexes in Therapeutics.

    PubMed

    Demkowicz, Sebastian; Kozak, Witold; Daśko, Mateusz; Rachon, Janusz

    2016-01-01

    The present mini-review highlights recent developments on antitumor activity of metal-based therapeutics which have been a subject of researches for the last few decades. In 1965, Rosenberg found that during an electrolysis on platinum electrodes a complex of Pt is generated which inhibited to a great extent a binary fission in Escherichia coli bacteria. This discovery started a new chapter in medicinal chemistry and the interesting properties of cisplatin were soon applied in cancer therapy especially in curing genitourinary tumors. However, various side effects limited its use in medical treatment. Since then a great number of other metal-organic complexes based on platinum, palladium, ruthenium, gold, copper, silver, rhodium, osmium, rhenium, iridium and others have been synthesized. Among them, NAMI-A and KP1019 have recently undergone clinical trials. In this review paper we report a detailed account of metal complexes with phosphorus-based ligands which are of particular interest in therapeutics.

  3. [Therapeutic use of cannabis derivatives].

    PubMed

    Benyamina, Amine; Reynaud, Michel

    2014-02-01

    The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

  4. Horizontally staggered lightguide solar concentrator with lateral displacement tracking for high concentration applications.

    PubMed

    Ma, Hongcai; Wu, Lin

    2015-07-10

    We present the design of a horizontally staggered lightguide solar concentrator with lateral displacement tracking for high concentration applications. This solar concentrator consists of an array of telecentric primary concentrators, a horizontally staggered lightguide layer, and a vertically tapered lightguide layer. The primary concentrator is realized by two plano-aspheric lenses with lateral movement and maintains a high F-number over an angle range of ±23.5°. The results of the simulations show that the solar concentrator achieves a high concentration ratio of 500× with ±0.5° of acceptance angle by a single-axis tracker and dual lateral translation stages.

  5. Metacognition, Achievement Goals, Study Strategies and Academic Achievement: Pathways to Achievement

    ERIC Educational Resources Information Center

    Vrugt, Anneke; Oort, Frans J.

    2008-01-01

    The purpose of this research was to develop and test a model of effective self-regulated learning. Based on effort expenditure we discerned effective self-regulators and less effective self-regulators. The model comprised achievement goals (mastery, performance-approach and -avoidance goals), metacognition (metacognitive knowledge, regulation and…

  6. Thermodynamic aspects of therapeutic hypothermia.

    PubMed

    Vanlandingham, Sean C; Kurz, Michael C; Wang, Henry E

    2015-01-01

    Therapeutic hypothermia (TH) is an important treatment for post-cardiac arrest syndrome. Despite its widespread practice, only limited data describe the thermodynamic aspects of heat transfer during TH. This paper reviews the principles of human body heat balance and provides a conceptual model for characterizing heat exchange during TH. The model may provide a framework for computer simulation for improving training in or clinical methods of TH.

  7. Yessotoxin, a Promising Therapeutic Tool.

    PubMed

    Alfonso, Amparo; Vieytes, Mercedes R; Botana, Luis M

    2016-01-28

    Yessotoxin (YTX) is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications.

  8. Antibody Engineering and Therapeutics Conference

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Scott, Jamie; Larrick, James W; Plückthun, Andreas; Veldman, Trudi; Adams, Gregory P; Parren, Paul WHI; Chester, Kerry A; Bradbury, Andrew; Reichert, Janice M; Huston, James S

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Biology), who will discuss a systems approach for studying disease that is enabled by emerging technology; Douglas Lauffenburger (Massachusetts Institute of Technology), who will discuss systems analysis of cell communication network dynamics for therapeutic biologics design; David Baker (University of Washington), who will describe computer-based design of smart protein therapeutics; and William Schief (The Scripps Research Institute), who will discuss epitope-focused immunogen design.   In this preview of the conference, the workshop and session chairs share their thoughts on what conference participants may learn in sessions on: (1) three-dimensional structure antibody modeling; (2) identifying clonal lineages from next-generation data sets of expressed VH gene sequences; (3) antibodies in cardiometabolic medicine; (4) the effects of antibody gene variation and usage on the antibody response; (5) directed evolution; (6) antibody pharmacokinetics, distribution and off-target toxicity; (7) use of knowledge-based design to guide development of complementarity-determining regions and epitopes to engineer or elicit the desired antibody; (8) optimizing antibody formats for immunotherapy; (9) antibodies in a complex environment; (10) polyclonal, oligoclonal and bispecific antibodies; (11) antibodies to watch in 2014; and (12) polyreactive antibodies and polyspecificity.

  9. Therapeutic uses of contraceptive steroids.

    PubMed

    Starks, G C

    1984-09-01

    During the past 20 years, contraceptive steroids have undergone significant changes as the result of an increased understanding of their metabolic, pharmacologic, and hormonal activities. During this time, prospective and retrospective epidemiologic studies have elucidated several noncontraceptive health benefits of oral contraceptive steroids, including their therapeutic effects for endometriosis, dysmenorrhea, polycystic ovarian disease, and benign breast disease. From this review it appears that the benefits of oral contraceptive steroids in young, healthy, nonsmoking women far outweigh their more publicized, infrequent risks.

  10. Therapeutic Issues with Transgender Elders.

    PubMed

    Carroll, Lynne

    2017-03-01

    Research demonstrates that transgender and nonconforming (TGNC) elders face social isolation and discrimination in policies and practices in mental and health care settings. The purpose of this article is to provide clinicians with practical input about therapeutic issues and interventions for use with TGNC elders. A case vignette describes the challenges and rewards of therapy with an elder trans woman. Her story illustrates the complex interplay between age, life phase, and sociocultural and historical contexts. Recommendations regarding research, practice, and advocacy are offered.

  11. The incongruous achiever in adolescence.

    PubMed

    Kline, S A; Golombek, H

    1974-06-01

    The authors wished to study some of the internal psychological dynamics of achievement in a nonpatient identified high school population. Questionnaires were administered to the Grade 13 students and their parents in a large high school. A number of students whose achievement and educational plans were not congruous with their general background were selected for interview. The findings suggest that a wide variety of ages and developmental stages can be discerned as critical points in the development of a student's attitude toward higher education. These students have many values in common, and their values appear related to a positive or negative identification with parental values. The students themselves show a wide range of personality integration. They relate in a special way to a wide variety of teachers' personalities.

  12. Beam cooling: Principles and achievements

    SciTech Connect

    Mohl, Dieter; Sessler, Andrew M.

    2003-05-18

    After a discussion of Liouville's theorem, and its implications for beam cooling, a brief description is given of each of the various methods of beam cooling: stochastic, electron, radiation, laser, ionization, etc. For each, we present the type of particle for which it is appropriate, its range of applicability, and the currently achieved degree of cooling. For each method we also discuss the present applications and, also, possible future developments and further applications.

  13. Avian Diagnostic and Therapeutic Antibodies

    SciTech Connect

    Bradley, David Sherman

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  14. Conotoxins that confer therapeutic possibilities.

    PubMed

    Essack, Magbubah; Bajic, Vladimir B; Archer, John A C

    2012-06-01

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt(®); Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred.

  15. Therapeutic Strategies in Huntington's Disease

    PubMed Central

    2006-01-01

    This article provides an overview of the therapeutic strategies, from ordinary classical drugs to the modern molecular strategy at experimental level, for Huntington's disease. The disease is characterized by choreic movements, psychiatric disorders, striatal atrophy with selective small neuronal loss, and autosomal dominant inheritance. The genetic abnormality is CAG expansion in huntingtin gene. Mutant huntingtin with abnormally long glutamine stretch aggregates and forms intranuclear inclusions. In this review, I summarize the results of previous trials from the following aspects; 1. symptomatic/palliative therapies including drugs, stereotaxic surgery and repetitive transcranial magnetic stimulation, 2. anti-degenerative therapies including anti-excitotoxicity, reversal of mitochondrial dysfunction and anti-apoptosis, 3. restorative/reparative therapies including neural trophic factors and tissue or stem cell transplantation, and 4. molecular targets in specific and radical therapies including inhibition of truncation of huntingtin, inhibition of aggregate formation, normalization of transcriptional dysregulation, enhancement of autophagic clearance of mutant huntingtin, and specific inhibition of huntingtin expression by sRNAi. Although the strategies mentioned in the latter two categories are mostly at laboratory level at present, we are pleased that one can discuss such "therapeutic strategies", a matter absolutely impossible before the causal gene of Huntington's disease was identified more than 10 years ago. It is also true, however, that some of the "therapeutic strategies" mentioned here would be found difficult to implement and abandoned in the future. PMID:20396523

  16. Predicting educational achievement from DNA

    PubMed Central

    Selzam, S; Krapohl, E; von Stumm, S; O'Reilly, P F; Rimfeld, K; Kovas, Y; Dale, P S; Lee, J J; Plomin, R

    2017-01-01

    A genome-wide polygenic score (GPS), derived from a 2013 genome-wide association study (N=127,000), explained 2% of the variance in total years of education (EduYears). In a follow-up study (N=329,000), a new EduYears GPS explains up to 4%. Here, we tested the association between this latest EduYears GPS and educational achievement scores at ages 7, 12 and 16 in an independent sample of 5825 UK individuals. We found that EduYears GPS explained greater amounts of variance in educational achievement over time, up to 9% at age 16, accounting for 15% of the heritable variance. This is the strongest GPS prediction to date for quantitative behavioral traits. Individuals in the highest and lowest GPS septiles differed by a whole school grade at age 16. Furthermore, EduYears GPS was associated with general cognitive ability (~3.5%) and family socioeconomic status (~7%). There was no evidence of an interaction between EduYears GPS and family socioeconomic status on educational achievement or on general cognitive ability. These results are a harbinger of future widespread use of GPS to predict genetic risk and resilience in the social and behavioral sciences. PMID:27431296

  17. Therapeutic monitoring of clozapine in Australia: the need for consensus.

    PubMed

    Oo, Thein Z; Wilson, John F; Naidoo, Divania; Chetty, Manoranjenni

    2006-10-01

    In the absence of well-defined guidelines for the monitoring of plasma concentrations of clozapine, this study examined the practices of seven laboratories from four states in Australia. Laboratories analyzed 5 freeze-dried serum samples containing a mixture of clozapine and norclozapine in varying concentrations and the measurement data were analyzed for accuracy and precision. Additional information on laboratory practices was obtained through questionnaire responses. Measurement precision amongst the laboratories was good but there were significant differences in the accuracy of measurements from one laboratory. There were differences in the ranges for which assays had been validated and in suggested therapeutic ranges. These differences could have a significant impact on the interpretation of measured concentrations and patient care, and emphasize the need for consensus in this area. Repeat concentration measurements are recommended in the case of drug concentration measurements that are inconsistent with clinical observations or previous measurements.

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

    PubMed

    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.

  19. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    SciTech Connect

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  20. Theoretical maximum concentration factors for solar concentrators

    SciTech Connect

    Nicolas, R.O.; Duran, J.C.

    1984-11-01

    The theoretical maximum concentration factors are determined for different definitions of the factor for two-dimensional and three-dimensional solar concentrators that are valid for any source with nonuniform intensity distribution. Results are obtained starting from those derived by Winston (1970) for Lambertian sources. In particular, maximum concentration factors for three models of the solar-disk intensity distribution are calculated. 12 references.

  1. Si concentrator solar cell development. [Final report

    SciTech Connect

    Krut, D.D.

    1994-10-01

    This is the final report of a program to develop a commercial, high-efficiency, low-cost concentrator solar cell compatible with Spectrolab`s existing manufacturing infrastructure for space solar cells. The period covered is between 1991 and 1993. The program was funded through Sandia National Laboratories through the DOE concentrator initiative and, was also cost shared by Spectrolab. As a result of this program, Spectrolab implemented solar cells achieving an efficiency of over 19% at 200 to 300X concentration. The cells are compatible with DOE guidelines for a cell price necessary to achieve a cost of electricity of 12 cents a kilowatthour.

  2. [Therapeutic errors and dose measuring devices].

    PubMed

    García-Tornel, S; Torrent, M L; Sentís, J; Estella, G; Estruch, M A

    1982-06-01

    In order to investigate the possibilities of therapeutical error in syrups administration, authors have measured the capacity of 158 home spoons (x +/- SD). They classified spoons in four groups: group I (table spoons), 49 units (11.65 +/- 2.10 cc); group II (tea spoons), 41 units (4.70+/-1.04 cc); group III (coffee spoons), 41 units (2.60 +/- 0.59 cc), and group IV (miscellaneous), 27 units. They have compared the first three groups with theoreticals values of 15, 5 and 2.5 cc, respectively, ensuring, in the first group, significant statistical differences. In this way, they analyzed information that paediatricians receive from "vademecums", which they usually consult and have studied two points: If syrup has a meter or not, and if it indicates drug concentration or not. Only a 18% of the syrups have a meter and about 88% of the drugs indicate their concentration (mg/cc). They conclude that to prevent errors of dosage, the pharmacological industry must include meters in their products. If they haven't the safest thing is to use syringes.

  3. Achieving Global Ocean Color Climate Data Records

    NASA Technical Reports Server (NTRS)

    Franz, Bryan

    2010-01-01

    Ocean color, or the spectral distribution of visible light upwelling from beneath the ocean surface, carries information on the composition and concentration of biological constituents within the water column. The CZCS mission in 1978 demonstrated that quantitative ocean color measurements could be. made from spaceborne sensors, given sufficient corrections for atmospheric effects and a rigorous calibration and validation program. The launch of SeaWiFS in 1997 represents the beginning of NASA's ongoing efforts to develop a continuous ocean color data record with sufficient coverage and fidelity for global change research. Achievements in establishing and maintaining the consistency of the time-series through multiple missions and varying instrument designs will be highlighted in this talk, including measurements from NASA'S MODIS instruments currently flying on the Terra and Aqua platforms, as well as the MERIS sensor flown by ESA and the OCM-2 sensor recently launched by ISRO.

  4. The neural basis of academic achievement motivation.

    PubMed

    Mizuno, Kei; Tanaka, Masaaki; Ishii, Akira; Tanabe, Hiroki C; Onoe, Hirotaka; Sadato, Norihiro; Watanabe, Yasuyoshi

    2008-08-01

    We have used functional magnetic resonance imaging to study the neural correlates of motivation, concentrating on the motivation to learn and gain monetary rewards. We compared the activation in the brain obtained during reported high states of motivation for learning, with the ones observed when the motivation was based on monetary reward. Our results show that motivation to learn correlates with bilateral activity in the putamen, and that the higher the reported motivation, as derived from a questionnaire that each subject filled prior to scanning, the greater the change in the BOLD signals within the putamen. Monetary motivation also activated the putamen bilaterally, though the intensity of activity was not related to the monetary reward. We conclude that the putamen is critical for motivation in different domains and the extent of activity of the putamen may be pivotal to the motivation that drives academic achievement and thus academic successes.

  5. Current issues of RNAi therapeutics delivery and development.

    PubMed

    Haussecker, D

    2014-12-10

    12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that

  6. Social–Emotional Factors Affecting Achievement Outcomes Among Disadvantaged Students: Closing the Achievement Gap

    PubMed Central

    Becker, Bronwyn E.; Luthar, Suniya S.

    2012-01-01

    Despite concentrated efforts at improving inferior academic outcomes among disadvantaged students, a substantial achievement gap between the test scores of these students and others remains (Jencks & Phillips, 1998; National Center for Education Statistics, 2000a, 2000b; Valencia & Suzuki, 2000). Existing research used ecological models to document social–emotional factors at multiple levels of influence that undermine academic performance. This article integrates ideas from various perspectives in a comprehensive and interdisciplinary model that will inform policy makers, administrators, and schools about the social–emotional factors that act as both risk and protective factors for disadvantaged students’ learning and opportunities for academic success. Four critical social–emotional components that influence achievement performance (academic and school attachment, teacher support, peer values, and mental health) are reviewed. PMID:23255834

  7. Pharmacokinetics, pharmacodynamics and therapeutics of pradofloxacin in the dog and cat.

    PubMed

    Lees, P

    2013-06-01

    Pradofloxacin is a third-generation fluoroquinolone, licensed in the EU for use in a range of indications in the dog and cat and authorized more recently in the USA for one therapeutic indication (skin infections) in the cat. This review summarizes and appraises current knowledge on the physico-chemical, pharmacological [pharmacokinetics (PK) and pharmacodynamics (PD)], safety and therapeutic properties of pradofloxacin in the target species. Pradofloxacin contains two centres of asymmetry and is the pure SS enantiomer. After oral dosing of tablets (dog) or tablets and oral suspension (cat), maximum plasma concentrations (Cmax ) are achieved in less than 3.0 h, and terminal half-life is of the order of 5-10 h. Accumulation is slight or absent with once daily oral dosing. Free drug concentrations in plasma are in the range of 63-71% of total concentration. As for other fluoroquinolones, antibacterial activity is attributable to inhibition of bacterial replication at two sites, subunit A of topoisomerase II and topoisomerase IV. The antimicrobial spectrum includes gram-negative and gram-positive organisms, anaerobes, Mycoplasma spp. and some intracellular organisms (Rickettsia spp. and Mycobacterium spp.). The killing action is of the concentration-dependent type. Pradofloxacin has high potency (low MIC values) in comparison with first- and second-generation fluoroquinolones. Integration of in vivo PK and in vitro PD data provides values of Cmax /MIC and area under plasma concentration-time curve (AUC24 h )/MIC ratios predictive of good clinical efficacy against sensitive organisms, when administered at recommended dose rates. Clinical trial evaluation of pradofloxacin, in comparison with other authorized antimicrobial drugs, has demonstrated either noninferiority or superiority of pradofloxacin. Data indicating clinical and, in some instances, bacteriological cure have been reported: (i) in cats, for wound infections, abscesses, upper respiratory tract infections

  8. Updates and achievements in virology.

    PubMed

    Buonaguro, Franco M; Campadelli-Fiume, Gabriella; De Giuli Morghen, Carlo; Palù, Giorgio

    2010-07-01

    The 4th European Congress of Virology, hosted by the Italian Society for Virology, attracted approximately 1300 scientists from 46 countries worldwide. It also represented the first conference of the European Society for Virology, which was established in Campidoglio, Rome, Italy in 2009. The main goal of the meeting was to share research activities and results achieved in European virology units/institutes and to strengthen collaboration with colleagues from both western and developing countries. The worldwide representation of participants is a testament to the strength and attraction of European virology. The 5-day conference brought together the best of current virology; topics covered all three living domains (bacteria, archaea and eucarya), with special sessions on plant and veterinary virology as well as human virology, including two oral presentations on mimiviruses. The conference included five plenary sessions, 31 workshops, one hepatitis C virus roundtable, ten special workshops and three poster sessions, as well as 45 keynote lectures, 191 oral presentations and 845 abstracts. Furthermore, the Gesellschaft fur Virologie Loeffler-Frosch medal award was given to Peter Vogt for his long-standing career and achievements; the Gardner Lecture of the European Society for Clinical Virology was presented by Yoshihiro Kawaoka, and the Pioneer in Virology Lecture of the Italian Society for Virology was presented by Ulrich Koszinowski.

  9. Achieving permanency for LGBTQ youth.

    PubMed

    Jacobs, Jill; Freundlich, Madelyn

    2006-01-01

    This article brings together two significant efforts in the child welfare field: achieving permanence for youth in out-of-home care and meeting the needs of lesbian, gay, bisexual, transgender and questioning (LGBTQ) youth. During the past several years, a national movement has taken place to assure all children and youth have a permanent family connection before leaving the child welfare system; however, LGBTQ youth are not routinely included in the permanency discussions. At the same time, efforts in addressing the needs of LGBTQ youth have increased, but permanency is rarely mentioned as a need. This article offers models of permanence and practices to facilitate permanence with LGBTQ youth and their families. It also offers a youth-driven, individualized process, using youth development principles to achieve relational, physical, and legal permanence. Reunification efforts are discussed, including services, supports, and education required for youth to return to their family of origin. For those who cannot return home, other family resources are explored. The article also discusses cultural issues as they affect permanence for LGBTQ youth, and, finally, addresses the need for ongoing support services to sustain and support permanency.

  10. Bioengineering Lantibiotics for Therapeutic Success

    PubMed Central

    Field, Des; Cotter, Paul D.; Hill, Colin; Ross, R. P.

    2015-01-01

    Several examples of highly modified antimicrobial peptides have been described. While many such peptides are non-ribosomally synthesized, ribosomally synthesized equivalents are being discovered with increased frequency. Of the latter group, the lantibiotics continue to attract most attention. In the present review, we discuss the implementation of in vivo and in vitro engineering systems to alter, and even enhance, the antimicrobial activity, antibacterial spectrum and physico-chemical properties, including heat stability, solubility, diffusion and protease resistance, of these compounds. Additionally, we discuss the potential applications of these lantibiotics for use as therapeutics. PMID:26640466

  11. [Hereditary angioedema: a therapeutic revolution].

    PubMed

    Bouillet, L

    2012-03-01

    Hereditary angioedema is a rare disease, often diagnosed with delay because of a heterogeneous clinical presentation. Before diagnosis, patients frequently present subcutaneous edema or abdominal pains during many years. Laryngeal edema can be life-threatening. Hereditary angioedema may impair the quality of life of the patients and their social and professional life. It is important that the physicians recognize and treat the disease as soon as possible after the first attacks. Since the past five years, new drugs developed for hereditary angioedema have changed dramatically the outcome of this disorder. The objective of this review is to detail the new therapeutic guidelines.

  12. Imaging of prehospital stroke therapeutics

    PubMed Central

    Lin, Michelle P; Sanossian, Nerses; Liebeskind, David S

    2016-01-01

    Despite significant quality improvement efforts to streamline in-hospital acute stroke care in the conventional model, there remain inherent layers of treatment delays, which could be eliminated with prehospital diagnostics and therapeutics administered in a mobile stroke unit. Early diagnosis using Telestroke and neuroimaging while in the ambulance may enable targeted routing to hospitals with specialized care, which will likely improve patient outcomes. Key clinical trials in Telestroke, mobile stroke units with prehospital neuroimaging capability, prehospital ultrasound and co-administration of various classes of neuroprotectives, antiplatelets and antithrombin agents with intravenous thrombolysis are discussed in this article. PMID:26308602

  13. Therapeutic Strategies to Inhibit MYC

    PubMed Central

    McKeown, Michael R.; Bradner, James E.

    2014-01-01

    MYC is a master regulator of stem cell state, embryogenesis, tissue homeostasis, and aging. As in health, in disease MYC figures prominently. Decades of biological research have identified a central role for MYC in the pathophysiology of cancer, inflammation, and heart disease. The centrality of MYC to such a vast breadth of disease biology has attracted significant attention to the historic challenge of developing inhibitors of MYC. This review will discuss therapeutic strategies toward the development of inhibitors of MYC-dependent transcriptional signaling, efforts to modulate MYC stability, and the elusive goal of developing potent, direct-acting inhibitors of MYC. PMID:25274755

  14. Therapeutic Applications of Ionizing Radiations

    NASA Astrophysics Data System (ADS)

    Sánchez-Santos, María Elena

    The aim of radiation therapy is to deliver a precisely measured dose of radiation to a defined tumour volume with minimal damage to the surrounding healthy tissue, resulting in the eradication of the tumour, a higher quality of life with palliation of symptoms of the disease, and the prolongation of survival at competitive cost. Together with surgery and pharmacology, radiotherapy is presently one of the most important therapeutical weapons against cancer. This chapter provides an overview of the clinical use of radiation, with emphasis on the optimisation of treatment planning and delivery, and a top level summary of state-of-the-art techniques in radiation therapy.

  15. Exploring breast with therapeutic ductoscopy

    PubMed Central

    Feldman, Sheldon Marc

    2014-01-01

    Breast lesions are thought to arise mostly from the epithelium of ductal lining. Conventional imaging could only show indirect images of suspected lesions which are confirmed by percutaneous biopsies. However, ductoscopy provides direct images of the ductal epithelium which is the source of most malignant and papillary lesions. As an advance of current ductoscopy systems, pathologic nipple discharge (PND) could be treated ductoscopically by miniaturized endo-baskets or wires. Our goal is to discuss current intraductal technology which enables diagnostic and therapeutic advance for breast lesions that cause nipple discharge. PMID:25083507

  16. Glycan analysis of therapeutic glycoproteins

    PubMed Central

    Zhang, Lei; Luo, Shen; Zhang, Baolin

    2016-01-01

    ABSTRACT Therapeutic monoclonal antibodies (mAbs) are glycoproteins produced by living cell systems. The glycan moieties attached to the proteins can directly affect protein stability, bioactivity, and immunogenicity. Therefore, glycan variants of a glycoprotein product must be adequately analyzed and controlled to ensure product quality. However, the inherent complexity of protein glycosylation poses a daunting analytical challenge. This review provides an update of recent advances in glycan analysis, including the potential utility of lectin-based microarray for high throughput glycan profiling. Emphasis is placed on comparison of the major types of analytics for use in determining unique glycan features such as glycosylation site, glycan structure, and content. PMID:26599345

  17. Exploring breast with therapeutic ductoscopy.

    PubMed

    Balci, Fatih Levent; Feldman, Sheldon Marc

    2014-05-01

    Breast lesions are thought to arise mostly from the epithelium of ductal lining. Conventional imaging could only show indirect images of suspected lesions which are confirmed by percutaneous biopsies. However, ductoscopy provides direct images of the ductal epithelium which is the source of most malignant and papillary lesions. As an advance of current ductoscopy systems, pathologic nipple discharge (PND) could be treated ductoscopically by miniaturized endo-baskets or wires. Our goal is to discuss current intraductal technology which enables diagnostic and therapeutic advance for breast lesions that cause nipple discharge.

  18. New horizons in therapeutic antibody discovery: opportunities and challenges versus small-molecule therapeutics.

    PubMed

    Smith, Alison J

    2015-04-01

    Antibody drugs have become an increasingly significant component of the therapeutic landscape. Their success has been driven by some of their unique properties, in particular their very high specificity and selectivity, in contrast to the off-target liabilities of small molecules (SMs). Antibodies can bring additional functionality to the table with their ability to interact with the immune system, and this can be further manipulated with advances in antibody engineering. This review summarizes what antibody therapeutics have achieved to date and what opportunities and challenges lie ahead. The target landscape for large molecules (LMs) versus SMs and some of the challenges for antibody drug development are discussed. Effective penetration of membrane barriers and intracellular targeting is one challenge, particularly across the highly resistant blood-brain barrier. The expanding pipeline of antibody-drug conjugates offers the potential to combine SM and LM modalities in a variety of creative ways, and antibodies also offer exciting potential to build bi- and multispecific molecules. The ability to pursue more challenging targets can also be further exploited but highlights the need for earlier screening in functional cell-based assays. I discuss how this might be addressed given the practical constraints imposed by high-throughput screening sample type and process differences in antibody primary screening.

  19. Activities of Therapeutic Agents and Myristamidopropyl Dimethylamine against Acanthamoeba Isolates

    PubMed Central

    Kilvington, Simon; Hughes, Reanne; Byas, James; Dart, John

    2002-01-01

    The activities of therapeutic agents and myristamidopropyl dimethylamine (MAPD) against Acanthamoeba strains recalcitrant to medical therapy were studied. MAPD minimum cysticidal concentrations were 6.25 to 25 μg/ml; 10 to 30 μg/ml gave at least a 3-log cyst kill after 6 h, and 50 and 100 μg/ml gave at least a 3-log cyst kill within 2 and 1 h, respectively. PMID:12019127

  20. Activities of therapeutic agents and myristamidopropyl dimethylamine against Acanthamoeba isolates.

    PubMed

    Kilvington, Simon; Hughes, Reanne; Byas, James; Dart, John

    2002-06-01

    The activities of therapeutic agents and myristamidopropyl dimethylamine (MAPD) against Acanthamoeba strains recalcitrant to medical therapy were studied. MAPD minimum cysticidal concentrations were 6.25 to 25 microg/ml; 10 to 30 microg/ml gave at least a 3-log cyst kill after 6 h, and 50 and 100 microg/ml gave at least a 3-log cyst kill within 2 and 1 h, respectively.

  1. Therapeutic Wilderness Programs: A National Survey.

    ERIC Educational Resources Information Center

    Davis-Berman, Jennifer; And Others

    1994-01-01

    Examination of 31 therapeutic wilderness programs specializing in mental health treatment revealed that most programs served high-risk youth using a variety of outdoor modalities; that there was not a consensus on the definition of therapeutic; and that, in most cases, nonprofessional staff were responsible for therapeutic interventions. (LP)

  2. EXETRA Perspectives: Concepts in Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Neal, Larry L.; Edginton, Christopher R.

    Fifteen papers address issues in therapeutic recreation for disabled persons from the perspectives of practitioners, educators, and students. The following papers are presented. "Therapeutic Recreation Service: The Past and Challenging Present" (H. Sessoms); "Therapeutic Recreatiion in an Era of Limits: A Crisis...A Challenge... An Opportunity"…

  3. Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: theory, fabrication, and applications

    PubMed Central

    Kim, Sung Jae; Song, Yong-Ak; Han, Jongyoon

    2010-01-01

    Recently, a new type of electrokinetic concentration devices has been developed in a microfluidic chip format, which allows efficient trapping and concentration of biomolecules by utilizing ion concentration polarization near nanofluidic structures. These devices have drawn much attention not only due to their potential application in biomolecule sensing, but also due to the rich scientific content related to ion concentration polarization, the underlying physical phenomenon for the operation of these electrokinetic concentration devices. This tutorial review provides an introduction to the scientific and engineering advances achieved, in-depth discussion about several interesting applications of these unique concentration devices, and their current limitations and challenges. PMID:20179814

  4. Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections

    PubMed Central

    Díez-Martínez, Roberto; García-Fernández, Esther; Manzano, Miguel; Martínez, Ángel; Domenech, Mirian; Vallet-Regí, María; García, Pedro

    2016-01-01

    Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using a zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections. PMID:26776881

  5. Harnessing telomerase in cancer therapeutics.

    PubMed

    Fakhoury, Johans; Nimmo, Graeme A M; Autexier, Chantal

    2007-07-01

    Telomerase is an attractive target for anti-cancer therapeutics due to its requirement for cellular immortalization and expression in greater than 85% of human neoplasms. Though initially promising, strategies that inhibit telomerase with either small molecules or antisense oligonucleotides have a major limitation, namely the lag time required for telomere shortening before cellular effects are attained. As alternative approaches, immunotherapy and gene therapy have been tailored to exploit, rather than antagonize telomerase expression and/or activity. Immunotherapy requires the presence of the catalytic subunit of telomerase, hTERT, to elicit an immune response directed towards hTERT peptide-presenting cells. hTERT promoter-driven gene therapy and mutant telomerase RNA (hTR) gene therapy depend on the innate telomerase activity of cancer cells to drive the expression of pro-apoptotic genes and to synthesize mutated DNA sequences onto telomeres, respectively. In addition, we will discuss telomestatin, a G-quadruplex binding ligand that may exert anti-proliferative effects independently of telomere shortening. In this review, the progress, advantages, and limitations of these strategies in the ongoing effort to develop clinically relevant telomerase-based cancer therapeutics will be examined.

  6. Therapeutics in duchenne muscular dystrophy.

    PubMed

    Strober, Jonathan B

    2006-04-01

    Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3,500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

  7. Therapeutic Robotics: A Technology Push

    PubMed Central

    Krebs, Hermano Igo; Hogan, Neville

    2009-01-01

    In this paper, we present a retrospective and chronological review of our efforts to revolutionize the way physical medicine is practiced by developing and deploying therapeutic robots. We present a sample of our clinical results with well over 300 stroke patients, both inpatients and outpatients, proving that movement therapy has a measurable and significant impact on recovery following brain injury. Bolstered by this result, we embarked on a two-pronged approach: 1) to determine what constitutes best therapy practice and 2) to develop additional therapeutic robots. We review our robots developed over the past 15 years and their unique characteristics. All are configured both to deliver reproducible therapy but also to measure outcomes with minimal encumbrance, thus providing critical measurement tools to help unravel the key question posed under the first prong: what constitutes “best practice”? We believe that a “gym” of robots like these will become a central feature of physical medicine and the rehabilitation clinic within the next ten years. PMID:19779587

  8. Therapeutic equivalents in clinical practice.

    PubMed

    Benson, M D

    2001-01-01

    With increasing debate over the rising expenses of health care, a variety of cost-saving measures has been attempted over the years. Use of primary care physicians as "gate keepers," reduction in the length of hospital stays, and pushing women toward vaginal birth after Cesarean section have all been utilized despite on going issues with patient satisfaction and even safety. One remarkable success in stretching health-care dollars that has often been overlooked is the prescription of therapeutic equivalents, or generic drugs. Although available on a limited basis for decades, off-brand manufacture of pharmaceuticals with identical active ingredients as those of the branded drug received a large boost through Congressional legislation in 1984 with the Hatch-Waxman Act. "Fast-track" FDA approval was initiated by Congress to introduce competition into the marketplace for drugs whose patients had expired. While giving close scrutiny to the manufacturing process and requiring the same level of regulatory supervision for factors such as bioavailability and shelf life, the Hatch-Waxman Act removed the burden and expense from generic manufacturers of proving the safety and efficacy all over again of a previously FDA-approved drug. With less than a 20% market share of all prescribed drugs in 1984, the generic drug industry has captured roughly 44% of the market in recent years while accounting for only 8% of expenditures on prescription medication. The prescription of therapeutic equivalents is one method of keeping health care costs down without compromising patient satisfaction or safety.

  9. Current topics in therapeutic plasmapheresis.

    PubMed

    Nakanishi, Takeshi; Suzuki, Naoki; Kuragano, Takahiro; Nagasawa, Yasuyuki; Hasuike, Yukiko

    2014-02-01

    Therapeutic plasmapheresis has been used for intractable diseases that cannot be cured by conventional drug therapy. Currently, the use of therapeutic plasmapheresis has been approved for 27 diseases by Japan's National Health Insurance system and is mainly categorized into three modalities: plasma exchange (PE), double-filtration plasmapheresis (DFPP), and plasma adsorption (PA). Plasma separators and/or fractionators are essential for the therapy. PE is performed for two purposes: removal of pathogenic antigens or substances in the plasma fraction and supplementation of essential factors, such as albumin and coagulation factors. PE can be used for thrombotic microangiopathy and acute hepatic failure. DFPP can be performed for selective removal of macromolecules while avoiding the use of substitution fluid (i.e., albumin or fresh frozen plasma). DFPP has now been used for conditions involving relatively larger plasma molecules, including hyperviscosity syndrome and ABO-incompatible kidney transplantation. PA can specifically remove pathogenic agents, such as low-density lipoprotein or autoantibodies, in the IgG fractions by the adsorption column and does not require substitution fluids. PA has now been used for a wide variety of neurological diseases, including chronic inflammatory demyelinating polyneuropathy. This review describes the characteristics of each modality, seeking to improve the efficacy and specificity of removal of the target substance.

  10. Neuroinflammation: a potential therapeutic target.

    PubMed

    Craft, Jeffrey M; Watterson, D Martin; Van Eldik, Linda J

    2005-10-01

    The increased appreciation of the importance of glial cell-propagated inflammation (termed 'neuroinflammation') in the progression of pathophysiology for diverse neurodegenerative diseases, has heightened interest in the rapid discovery of neuroinflammation-targeted therapeutics. Efforts include searches among existing drugs approved for other uses, as well as development of novel synthetic compounds that selectively downregulate neuroinflammatory responses. The use of existing drugs to target neuroinflammation has largely met with failure due to lack of efficacy or untoward side effects. However, the de novo development of new classes of therapeutics based on targeting selective aspects of glia activation pathways and glia-mediated pathophysiologies, versus targeting pathways of quantitative importance in non-CNS inflammatory responses, is yielding promising results in preclinical animal models. The authors briefly review selected clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation as a pathophysiological process contributing to onset or progression of neurodegenerative diseases. The authors conclude with opinions based on recent experimental proofs of concept using preclinical animal models of pathophysiology. The focus is on Alzheimer's disease, but the concepts are transferrable to other neurodegenerative disorders with an inflammatory component.

  11. [Therapeutic Aggressiveness and Liquid Oncology].

    PubMed

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  12. Therapeutic targeting of bile acids

    PubMed Central

    Gores, Gregory J.

    2015-01-01

    The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID:26138466

  13. Achieving Quality in Occupational Health

    NASA Technical Reports Server (NTRS)

    O'Donnell, Michele (Editor); Hoffler, G. Wyckliffe (Editor)

    1997-01-01

    The conference convened approximately 100 registered participants of invited guest speakers, NASA presenters, and a broad spectrum of the Occupational Health disciplines representing NASA Headquarters and all NASA Field Centers. Centered on the theme, "Achieving Quality in Occupational Health," conferees heard presentations from award winning occupational health program professionals within the Agency and from private industry; updates on ISO 9000 status, quality assurance, and information technologies; workshops on ergonomics and respiratory protection; an overview from the newly commissioned NASA Occupational Health Assessment Team; and a keynote speech on improving women's health. In addition, NASA occupational health specialists presented 24 poster sessions and oral deliveries on various aspects of current practice at their field centers.

  14. Temozolomide analogs with improved brain/plasma ratios - Exploring the possibility of enhancing the therapeutic index of temozolomide.

    PubMed

    Rai, Roopa; Banerjee, Monali; Wong, Darren H; McCullagh, Emma; Gupta, Ashu; Tripathi, Shailendra; Riquelme, Eduardo; Jangir, Ramnivas; Yadav, Shyamraj; Raja, Mohd; Melkani, Pankaj; Dixit, Vikas; Patil, Umesh; Shrivastava, Ritesh; Middya, Sandip; Olivares, Felipe; Guerrero, Javier; Surya, Arjun; Pham, Son M; Bernales, Sebastián; Protter, Andrew A; Hung, David T; Chakravarty, Sarvajit

    2016-10-15

    Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O(6)-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain:plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma.

  15. The effects of chronic achievement motivation and achievement primes on the activation of achievement and fun goals.

    PubMed

    Hart, William; Albarracín, Dolores

    2009-12-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation.

  16. The Effects of Chronic Achievement Motivation and Achievement Primes on the Activation of Achievement and Fun Goals

    PubMed Central

    Hart, William; Albarracín, Dolores

    2013-01-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation. PMID:19968423

  17. A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

    ERIC Educational Resources Information Center

    Williams, Todd O.

    2012-01-01

    A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

  18. A review on therapeutic contact lenses for ocular drug delivery.

    PubMed

    Maulvi, Furqan A; Soni, Tejal G; Shah, Dinesh O

    2016-10-01

    Contact lenses for ophthalmic drug delivery have become very popular, due to their unique advantages like extended wear and more than 50% bioavailability. To achieve controlled and sustained drug delivery from contact lenses, researchers are working on various systems like polymeric nanoparticles, microemulsion, micelle, liposomes, use of vitamin E, etc. Numerous scientists are working on different areas of therapeutic contact lenses to treat ocular diseases by implementing techniques like soaking method, molecular imprinting, entrapment of drug-laden colloidal nanoparticles, drug plate/film, ion ligand polymeric systems, supercritical fluid technology, etc. Though sustained drug delivery was achieved using contact lens, the critical properties such as water content, tensile strength (mechanical properties), ion permeability, transparency and oxygen permeability were altered, which limit the commercialization of therapeutic contact lenses. Also issues like drug stability during processing/fabrication (drug integrity test), zero order release kinetics (prevent burst release), drug release during monomer extraction step after fabrication (to remove un-reacted monomers), protein adherence, drug release during storage in packaging solution, shelf life study, cost-benefit analysis, etc. are still to be addressed. This review provides an expert opinion on different methodology to develop therapeutic contact lenses with special remark of their advantages and limitations.

  19. Design and Evaluation of the Highly Concentrated Human IgG Formulation Using Cyclodextrin Polypseudorotaxane Hydrogels.

    PubMed

    Higashi, Taishi; Tajima, Anna; Ohshita, Naoko; Hirotsu, Tatsunori; Abu Hashim, Irhan Ibrahim; Motoyama, Keiichi; Koyama, Sawako; Iibuchi, Ruriko; Mieda, Shiuhei; Handa, Kenji; Kimoto, Tomoaki; Arima, Hidetoshi

    2015-12-01

    To achieve the potent therapeutic effects of human immunoglobulin G (IgG), highly concentrated formulations are required. However, the stabilization for highly concentrated human IgG is laborious work. In the present study, to investigate the potentials of polypseudorotaxane (PPRX) hydrogels consisting of polyethylene glycol (PEG) and α- or γ-cyclodextrin (α- or γ-CyD) as pharmaceutical materials for highly concentrated human IgG, we designed the PPRX hydrogels including human IgG and evaluated their pharmaceutical properties. The α- and γ-CyDs formed PPRX hydrogels with PEG (M.W. 20,000) even in the presence of highly concentrated human IgG (>100 mg/mL). According to the results of (1)H-NMR, powder X-ray diffraction, and Raman microscopy, the formation of human IgG/CyD PPRX hydrogels was based on physical cross-linking arising from their columnar structures. The release profiles of human IgG from the hydrogels were in accordance with the non-Fickian diffusion model. Importantly, the stabilities of human IgG included into the hydrogels against thermal and shaking stresses were markedly improved. These findings suggest that PEG/CyD PPRX hydrogels are useful to prepare the formulation for highly concentrated human IgG.

  20. Protein therapeutics: a summary and pharmacological classification.

    PubMed

    Leader, Benjamin; Baca, Quentin J; Golan, David E

    2008-01-01

    Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic--human insulin--25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. This article overviews some of the key characteristics of protein therapeutics, summarizes the more than 130 protein therapeutics used currently and suggests a new classification of these proteins according to their pharmacological action.

  1. Beyond amyloid: the future of therapeutics for Alzheimer's disease.

    PubMed

    Lane, Rachel F; Shineman, Diana W; Steele, John W; Lee, Linda Bobbi H; Fillit, Howard M

    2012-01-01

    Currently, the field is awaiting the results of several pivotal Phase III clinical Alzheimer's disease (AD) trials that target amyloid-β (Aβ). In light of the recent biomarker studies that indicate Aβ levels are at their most dynamic 5-10 years before the onset of clinical symptoms, it is becoming uncertain whether direct approaches to target Aβ will achieve desired clinical efficacy. AD is a complex neurodegenerative disease caused by dysregulation of numerous neurobiological networks and cellular functions, resulting in synaptic loss, neuronal loss, and ultimately impaired memory. While it is clear that Aβ plays a key role in the pathogenesis of AD, it may be a challenging and inefficient target for mid-to-late stage AD intervention. Throughout the course of AD, multiple pathways become perturbed, presenting a multitude of possible therapeutic avenues for design of AD intervention and prophylactic therapies. In this chapter, we sought to first provide an overview of Aβ-directed strategies that are currently in development, and the pivotal Aβ-targeted trials that are currently underway. Next, we delve into the biology and therapeutic designs associated with other key areas of research in the field including tau, protein trafficking and degradation pathways, ApoE, synaptic function, neurotrophic/neuroprotective strategies, and inflammation and energy utilization. For each area we have provided a comprehensive and balanced overview of the therapeutic strategies currently in preclinical and clinical development, which will shape the future therapeutic landscape of AD.

  2. Reversal of cognitive decline: A novel therapeutic program

    PubMed Central

    Bredesen, Dale E.

    2014-01-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  3. The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution.

    PubMed

    Dyawanapelly, Sathish; Junnuthula, Vijayabhaskar Reddy; Singh, AkhileshVikram

    2015-01-01

    In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

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

    ERIC Educational Resources Information Center

    Alsharif, Naser Z.; And Others

    1997-01-01

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

  5. Achievement Monitoring of Individually Paced Instruction. Final Report.

    ERIC Educational Resources Information Center

    Pinsky, Paul D.

    A study was made to monitor achievement of individually paced instruction. The project concentrated on designing testing procedures in group paced instructional programs to provide information to student, teachers, parents and administrators which could be used in both a formative and summative evaluation. The three objectives of the project were:…

  6. Problems and Issues in Translating International Educational Achievement Tests

    ERIC Educational Resources Information Center

    Arffman, Inga

    2013-01-01

    The article reviews research and findings on problems and issues faced when translating international academic achievement tests. The purpose is to draw attention to the problems, to help to develop the procedures followed when translating the tests, and to provide suggestions for further research. The problems concentrate on the following: the…

  7. "Brains before "Beauty"?" High Achieving Girls, School and Gender Identities

    ERIC Educational Resources Information Center

    Skelton, Christine; Francis, Becky; Read, Barbara

    2010-01-01

    In recent years educational policy on gender and achievement has concentrated on boys' underachievement, frequently comparing it with the academic success of girls. This has encouraged a perception of girls as the "winners" of the educational stakes and assumes that they no longer experience the kinds of gender inequalities identified in…

  8. Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?

    PubMed Central

    Schäfer, Richard; Spohn, Gabriele; Baer, Patrick C.

    2016-01-01

    Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy. PMID:27721701

  9. Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

    PubMed

    Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

    2014-10-21

    Various therapeutics exhibit unfavorable physicochemical properties or stability issues that reduce their in vivo efficacy. Therefore, carriers able to overcome such challenges and deliver therapeutics to specific in vivo target sites are critically needed. For instance, anticancer drugs are hydrophobic and require carriers to solubilize them in aqueous environments, and gene-based therapies (e.g., siRNA or pDNA) require carriers to protect the anionic genes from enzymatic degradation during systemic circulation. Polymeric micelles, which are self-assemblies of amphiphilic polymers (APs), constitute one delivery vehicle class that has been investigated for many biomedical applications. Having a hydrophobic core and a hydrophilic shell, polymeric micelles have been used as drug carriers. While traditional APs are typically comprised of nondegradable block copolymers, sugar-based amphiphilic polymers (SBAPs) synthesized by us are comprised of branched, sugar-based hydrophobic segments and a hydrophilic poly(ethylene glycol) chain. Similar to many amphiphilic polymers, SBAPs self-assemble into polymeric micelles. These nanoscale micelles have extremely low critical micelle concentrations offering stability against dilution, which occurs with systemic administration. In this Account, we illustrate applications of SBAPs for anticancer drug delivery via physical encapsulation within SBAP micelles and chemical conjugation to form SBAP prodrugs capable of micellization. Additionally, we show that SBAPs are excellent at stabilizing liposomal delivery systems. These SBAP-lipid complexes were developed to deliver hydrophobic anticancer therapeutics, achieving preferential uptake in cancer cells over normal cells. Furthermore, these complexes can be designed to electrostatically complex with gene therapies capable of transfection. Aside from serving as a nanocarrier, SBAPs have also demonstrated unique bioactivity in managing atherosclerosis, a major cause of cardiovascular

  10. Level 1 Therapeutic Model site.

    PubMed

    Hall, Philip S; DeJong, Judith A

    2006-01-01

    This site is an intertribal residential grant school annually enrolling over 250 students in grades 1-8 from tribes located in three states on the Northern Great Plains. From its inception in 1890, the boarding school's mission has been to provide services for young children in need of a safe and supportive living and learning environment. For over a decade, this site has used strategies centered on respecting children, structuring students' time, and providing the therapeutic benefits of a well-maintained campus. This site also has a long history of believing in each child's inherent value and potential. When Therapeutic Residential Model funding commenced at the midpoint of the 2002-2003 school year, L1 focused these new resources on strengthening and refining its program. The number of personnel positions increased from 98 to 135, with new positions principally going to dormitory staff and four Masters-level counselor positions. This increase in staff allowed L1 to proactively address the children's developmental needs. The site also adopted and implemented the Applied Humanism caregiving model. In accordance with Applied Humanism, an interview was utilized that allowed the site to identify and hire applicants possessing the attitudes and skills necessary to be good caregivers, existing staff were trained so that they understood the kind of caregiving that would be expected of them, supervision procedures and practices were implemented that supported and encouraged good caregivers and provided time-limited assistance to those who were not, and relevant agency policies and procedures were revised as needed to align with the Applied Humanism philosophy. In addition, the Morningside program was brought in to systematically address the students' academic lags in reading. The results of implementing the Therapeutic Residential Model were a reduction in behavioral incidents, a decrease in the amount of money spent on external mental health services, an increase in the

  11. [Functional Analytic Psychotherapy: Approaches and scope of behavior therapy based on changes in the therapeutic context].

    PubMed

    Muñoz-Martínez, Amanda M; Coletti, Juan P

    2015-01-01

    Functional Analytic Psychotherapy (FAP) is a therapeutic approach developed in 'third wave therapies' context. FAP is characterized by use therapeutic relationship and the behaviors emit into it to improve clients daily life functioning. This therapeutic model is supported in behavior analysis principles and contextual functionalism philosophy. FAP proposes that clients behavior in session are functional equivalent with those out of session; therefore, when therapists respond to clients behaviors in session contingently, they promote and increase improvements in the natural setting. This article poses main features of FAP, its philosophical roots, achievements and research challenges to establish FAP as an independent treatment based on the evidence.

  12. [FUNCTIONAL ANALYTIC PSYCHOTHERAPY: APPROACHES AND SCOPE OF BEHAVIOR THERAPY BASED ON CHANGES IN THE THERAPEUTIC CONTEXT].

    PubMed

    Muñoz-Martínez, Amanda M; Coletti, Juan Pablo

    2015-01-01

    Abstract Functional Analytic Psychotherapy (FAP) is a therapeutic approach developed in context. FAP is characterized by use therapeutic relationship and the behaviors emit into it to improve clients daily life functioning. This therapeutic model is supported in behavior analysis principles and contextual functionalism philosophy. FAP proposes that clients behavior in session are functional equivalent with those out of session; therefore, when therapists respond to clients behaviors in session contingently, they promote and increase improvements in the natural setting. This article poses main features of FAP, its philosophical roots, achievements and research challenges to establish FAP as an independent treatment based on the evidence.

  13. Contact refusal by children following acrimonious separation: therapeutic approaches with children and parents.

    PubMed

    Dejong, Margaret; Davies, Hilary

    2013-04-01

    This paper aims to build on the existing literature, by presenting some thoughts based on clinical experience with nine families of children referred for intractable contact refusal with one parent following marital separation. This particular group of high-conflict divorce cases engenders an inordinate amount of frustration both within the courts and therapeutic agencies. We outline here our assessment process and therapeutic strategies, as well as consideration of the role of the wider professional system and the courts. We conclude that whether or not direct contact with the rejected parent is achieved, useful therapeutic work can be carried out to assist children in moving on with their lives.

  14. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

    PubMed

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-03-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

  15. HIV-1 Genital Shedding is Suppressed in the Setting of High Genital Antiretroviral Drug Concentrations Throughout the Menstrual Cycle

    PubMed Central

    Sheth, Anandi N.; Evans-Strickfaden, Tammy; Haaland, Richard; Martin, Amy; Gatcliffe, Chelsea; Adesoye, Adebola; Omondi, Michael W.; Lupo, L. Davis; Danavall, Damien; Easley, Kirk; Chen, Cheng-Yen; Pau, Chou-Pong; Hart, Clyde; Ofotokun, Igho

    2014-01-01

    Background. It is not known if fluctuations in genital tract antiretroviral drug concentrations correlate with genital virus shedding in human immunodeficiency virus (HIV)–infected women on antiretroviral therapy (ART). Methods. Among 20 HIV-infected women on ART (tenofovir [TFV], emtricitabine [FTC], and ritonavir-boosted atazanavir [ATV]) with suppressed plasma virus loads, blood and cervicovaginal samples collected twice weekly for 3 weeks were tested for antiretroviral concentrations, HIV-1 RNA, and proviral DNA. Results. Cervicovaginal:plasma antiretroviral concentration ratios were highest for FTC (11.9, 95% confidence interval [CI], 8.66–16.3), then TFV (3.52, 95% CI, 2.27–5.48), and ATV (2.39, 95% CI, 1.69–3.38). Within- and between-person variations in plasma and genital antiretroviral concentrations were observed. Low amounts of genital HIV-1 RNA (<50 copies/mL) were detected in 45% of women at 16% of visits. Genital HIV-1 DNA was detected in 70% of women at 35% of visits. Genital virus detection was associated with higher concentrations of mucosal leukocytes but not with genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding, or plasma virus detection. Conclusions. Standard doses of ART achieved higher genital than plasma concentrations across the menstrual cycle. Therapeutic ART suppresses genital virus shedding throughout the menstrual cycle, even in the presence of factors reported to increase virus shedding. PMID:24643223

  16. Therapeutic clowning in paediatric practice.

    PubMed

    Finlay, Fiona; Baverstock, Anna; Lenton, Simon

    2014-10-01

    Over the past 30 years, there has been much research into the health benefits of humour and laughter. Although often viewed very positively, rigorous evaluation of the therapeutic effect of clowning is complex. Clowning is a multi-modal intervention, which may have an impact on medical conditions, procedures, family functioning and health care teams. Clowns help children to adapt to their hospital surroundings and can distract from, and demystify, painful or frightening procedures through 'doses of fun' to complement traditional clinical interventions. This paper provides a review of the paediatric literature and reveals studies looking at the effect of clown interventions on various practical procedures and individual medical conditions, and the effects of clowning within clinical teams.

  17. Brain plasticity-based therapeutics

    PubMed Central

    Merzenich, Michael M.; Van Vleet, Thomas M.; Nahum, Mor

    2014-01-01

    The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, traditional clinical strategies of professional therapy practitioners, and (b) an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine. PMID:25018719

  18. Antibody engineering and therapeutics conference

    PubMed Central

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A; Burton, Dennis R; Adams, Gregory P; Weiner, Louis M; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2014-01-01

    The 25th anniversary of the Antibody Engineering & Therapeutics Conference, the Annual Meeting of The Antibody Society, will be held in Huntington Beach, CA, December 7–11, 2014. Organized by IBC Life Sciences, the event will celebrate past successes, educate participants on current activities and offer a vision of future progress in the field. Keynote addresses will be given by academic and industry experts Douglas Lauffenburger (Massachusetts Institute of Technology), Ira Pastan (National Cancer Institute), James Wells (University of California, San Francisco), Ian Tomlinson (GlaxoSmithKline) and Anthony Rees (Rees Consulting AB and Emeritus Professor, University of Bath). These speakers will provide updates of their work, placed in the context of the substantial growth of the industry over the past 25 years. PMID:25517297

  19. Ion channel therapeutics for pain

    PubMed Central

    Skerratt, Sarah E; West, Christopher W

    2015-01-01

    Pain is a complex disease which can progress into a debilitating condition. The effective treatment of pain remains a challenge as current therapies often lack the desired level of efficacy or tolerability. One therapeutic avenue, the modulation of ion channel signaling by small molecules, has shown the ability to treat pain. However, of the 215 ion channels that exist in the human genome, with 85 ion channels having a strong literature link to pain, only a small number of these channels have been successfully drugged for pain. The focus of future research will be to fully explore the possibilities surrounding these unexplored ion channels. Toward this end, a greater understanding of ion channel modulation will be the greatest tool we have in developing the next generation of drugs for the treatment of pain. PMID:26218246

  20. Proteopathy: the next therapeutic frontier?

    PubMed

    Walker, Lary C; LeVine, Harry

    2002-05-01

    The abnormal conformation and assembly of proteins is a probable cause of many degenerative diseases of old age. These proteopathies include such clinically disparate neurological disorders as Alzheimer's disease. Parkinson's disease and Creutzfeldt-Jakob disease, as well as a variety of non-neurological maladies. The involvement of protein pathology in these diseases is well established and we are beginning to understand the process whereby proteins self-assemble and injure tissues; however, we remain largely in the dark regarding the fundamental origins of the proteopathies. Our present knowledge suggests three broad therapeutic approaches to abrogating the proteopathic cascade: reduce the production of the offending proteins, prevent their self-assembly, or promote their removal.

  1. The delivery of therapeutic oligonucleotides

    PubMed Central

    Juliano, Rudolph L.

    2016-01-01

    The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology. PMID:27084936

  2. Therapeutic advances in muscular dystrophy

    PubMed Central

    Leung, Doris G; Wagner, Kathryn R

    2013-01-01

    The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Each of these disorders represents a different class of genetic disease (monogenic, epigenetic, and repeat expansion disorders), and the approach to therapy addresses the diverse and complex molecular mechanisms involved in these diseases. The large number of novel pharmacologic agents in development with good biologic rationale and strong proof of concept suggests there will be an improved quality of life for individuals with muscular dystrophy. PMID:23939629

  3. Therapeutic target for protozoal diseases

    DOEpatents

    Rathore, Dharmendar; Jani, Dewal; Nagarkatti, Rana

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  4. Current therapeutic paradigms in glioblastoma.

    PubMed

    Quick, Allison; Patel, Disha; Hadziahmetovic, Mersiha; Chakravarti, Arnab; Mehta, Minesh

    2010-01-01

    Glioblastoma (GBM), a WHO grade IV malignant glioma, is the most common and lethal adult primary brain tumor. Median survival rates range from 12-15 months. The current standard of care for GBM has evolved from resection followed by adjuvant radiotherapy to resection, concurrent adjuvant chemotherapy (temozolomide) and radiation, and additional adjuvant chemotherapy. The expression of specific molecular biomarkers, especially O-6-methylguanine methyltransferase (MGMT) status, may determine the response of the tumor to treatment, and helps in identifying the magnitude of benefit from this regimen. By identifying further biological subtypes of GBM at the molecular level, specific targeted therapies could be developed and used in the future for more individualized therapeutic regimens. This article will review the current therapies for GBM and the investigation of new molecular and targeted therapies, such as EGFR inhibitors, mTOR/PI3Kinase inhibitors, and anti-angiogenesis agents.

  5. Design of an ultrasmall aspect ratio concentrator

    NASA Astrophysics Data System (ADS)

    Cheng, Ying; Fang, Fengzhou; Zhang, Xiaodong

    2014-11-01

    The concentrated photovoltaic (CPV) can be employed to improve the efficiency of solar cells and reduce the system cost of power generation, which is the primary part of the CPV system. Based on the demands for the concentrators to have an ultrathin and ultralight design, a design of ultrasmall aspect ratio concentrators is proposed. The concentrator is formed by a lens array and a freeform reflector to precisely control the light. The solar cell is placed at the side of the concentrator, which greatly reduces the overall thickness of the concentrator. The design can reduce the aspect ratio of concentrator by a considerable amount. The freeform reflector can shape the light beam and achieve a uniform distribution of light energy.

  6. Competency-Based Achievement System

    PubMed Central

    Ross, Shelley; Poth, Cheryl N.; Donoff, Michel; Humphries, Paul; Steiner, Ivan; Schipper, Shirley; Janke, Fred; Nichols, Darren

    2011-01-01

    Abstract Problem addressed Family medicine residency programs require innovative means to assess residents’ competence in “soft” skills (eg, patient-centred care, communication, and professionalism) and to identify residents who are having difficulty early enough in their residency to provide remedial training. Objective of program To develop a method to assess residents’ competence in various skills and to identify residents who are having difficulty. Program description The Competency-Based Achievement System (CBAS) was designed to measure competence using 3 main principles: formative feedback, guided self-assessment, and regular face-to-face meetings. The CBAS is resident driven and provides a framework for meaningful interactions between residents and advisors. Residents use the CBAS to organize and review their feedback, to guide their own assessment of their progress, and to discern their future learning needs. Advisors use the CBAS to monitor, guide, and verify residents’ knowledge of and competence in important skills. Conclusion By focusing on specific skills and behaviour, the CBAS enables residents and advisors to make formative assessments and to communicate their findings. Feedback indicates that the CBAS is a user-friendly and helpful system to assess competence. PMID:21918129

  7. Academic Achievement Among Juvenile Detainees

    PubMed Central

    Grigorenko, Elena L.; Macomber, Donna; Hart, Lesley; Naples, Adam; Chapman, John; Geib, Catherine F.; Chart, Hilary; Tan, Mei; Wolhendler, Baruch; Wagner, Richard

    2016-01-01

    The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010–July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample (n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research. PMID:24064502

  8. Academic Achievement Among Juvenile Detainees.

    PubMed

    Grigorenko, Elena L; Macomber, Donna; Hart, Lesley; Naples, Adam; Chapman, John; Geib, Catherine F; Chart, Hilary; Tan, Mei; Wolhendler, Baruch; Wagner, Richard

    2015-01-01

    The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010-July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample (n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research.

  9. The pragmatics of therapeutic interaction: an empirical study.

    PubMed

    Lepper, Georgia

    2009-10-01

    The research reported in this article aims to demonstrate a method for the systematic study of the therapist/patient interaction in psychoanalytic psychotherapy, drawing upon the tradition and methods of 'pragmatics'--the study of language in interaction. A brief introduction to the discipline of pragmatics demonstrates its relevance to the contemporary focus of clinical theory on the here-and-now dynamics of the relationship between analyst and patient. This is followed by a detailed study of five segments from the transcript of a therapeutic dialogue, drawn from a brief psychoanalytic psychotherapy, in which therapist and patient negotiate the meaning of the patient's symptom: Is it psychosomatic? The research seeks to show how the therapeutic process can be observed and studied as an interactional achievement, grounded in general and well-studied procedures through which meaning is intersubjectively developed and shared. Implications of the analysis for clinical theory and practice, and further research, are discussed.

  10. Synthetic biology and therapeutic strategies for the degenerating brain

    PubMed Central

    Agustín-Pavón, Carmen; Isalan, Mark

    2014-01-01

    Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease-related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will arise from combining ‘protect and repair’ strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site-specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long-term therapies for many brain diseases in human patients. PMID:25100403

  11. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases.

    PubMed

    Lai, Yuping; Dong, Chen

    2016-04-01

    Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects.

  12. ANTIOXIDANT THERAPEUTIC ADVANCES IN COPD

    PubMed Central

    Rahman, Irfan

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD. PMID:19124382

  13. Emerging therapeutic options for asthma.

    PubMed

    Colice, Gene L

    2011-04-01

    Asthma is characterized by eosinophilic airway inflammation and elevated serum immunoglobulin E (IgE) levels. Due to these pathologic features, the foundation of asthma treatment has historically been anti-inflammatory therapy with inhaled corticosteroids (ICSs). Numerous factors in addition to IgE and eosinophils, however, likely play important roles in mediating the airway inflammatory response characteristic of asthma. ICSs are effective therapy for some patients with persistent asthma, but clinical trials have shown that even increasing doses of ICSs under carefully controlled situations does not always result in acceptable asthma control. Consequently, other classes of medications, in addition to ICSs, are recommended in those patients with more severe asthma. The class of medication most commonly used in more severe asthma, along with ICSs, is long-acting inhaled beta2-agonists, but leukotriene modifying agents and anti-IgE monoclonal antibodies may also be used. Agents such as tiotropium, a long-acting inhaled anti-muscarinic agent, and those aimed at inhibiting cytokines, such as mepoluzimab, daclizumab, and etanercept, hold promise in the treatment of asthma. Other agents under investigation include phosphodiesterase type 4 inhibitors and oligonucleotides. Bronchial thermoplasty, a nonpharmacologic option, may also be beneficial in patients with poorly controlled asthma. As our understanding of the complex pathophysiology of asthma increases, it will enable the development of novel therapeutic approaches for patients who are not responding well to traditional treatments. Although more studies are necessary to ensure the efficacy and safety of both pharmacologic and nonpharmacologic approaches, there is future promise for therapeutic advances in severe, persistent asthma.

  14. Direct Alloying of Steel with Nickel Concentrate

    NASA Astrophysics Data System (ADS)

    Nokhrina, O. I.; Rozhikhina, I. D.; Proshunin, I. E.

    2016-08-01

    A technology of alloying steel with nickel reduced from nickel concentrate is analysed and developed. Limits of reduction concentration areas are defined. An optimal composition of nickel concentrate pellets and a method of feeding them into the furnace are deduced from experiments. It is proved that when pellets made of nickel concentrate and coke are added into the charge during steel smelting by the technology of alloyed scrap remelting, nickel recovery achieves 92-95%. The technology was tested by smelting DSP-40 steel.

  15. Breast cancer stem cells, EMT and therapeutic targets

    SciTech Connect

    Kotiyal, Srishti; Bhattacharya, Susinjan

    2014-10-10

    Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.

  16. Sharing Leadership Responsibilities Results in Achievement Gains

    ERIC Educational Resources Information Center

    Armistead, Lew

    2010-01-01

    Collective, not individual, leadership in schools has a greater impact on student achievement; when principals and teachers share leadership responsibilities, student achievement is higher; and schools having high student achievement also display a vision for student achievement and teacher growth. Those are just a few of the insights into school…

  17. Closing the Achievement Gap: Challenges and Opportunities

    ERIC Educational Resources Information Center

    Robards, Shirley N.

    2008-01-01

    Closing the achievement gap between low- and high-achieving public school students is an important goal of public education. This article explores background information and research and discusses examples of best practices to close the achievement gap. Several plans have been proposed as ways to enhance the achievement of under-represented…

  18. Development of concentrator solar cells

    SciTech Connect

    Not Available

    1994-08-01

    A limited pilot production run on PESC silicon solar cells for use at high concentrations (200 to 400 suns) is summarized. The front contact design of the cells was modified for operation without prismatic covers. The original objective of the contract was to systematically complete a process consolidation phase, in which all the, process improvements developed during the contract would be combined in a pilot production run. This pilot run was going to provide, a basis for estimating cell costs when produced at high throughput. Because of DOE funding limitations, the Photovoltaic Concentrator Initiative is on hold, and Applied Solar`s contract was operated at a low level of effort for most of 1993. The results obtained from the reduced scope pilot run showed the effects of discontinuous process optimization and characterization. However, the run provided valuable insight into the technical areas that can be optimized to achieve the original goals of the contract.

  19. Silicon concentrator solar cell research

    SciTech Connect

    Green, M.A.; Zhao, J.; Wang, A.; Dai, X.; Milne, A.; Cai, S.; Aberle, A.; Wenham, S.R.

    1993-06-01

    This report describes work conducted between December 1990 and May 1992 continuing research on silicon concentrator solar cells. The objectives of the work were to improve the performance of high-efficiency cells upon p-type substrates, to investigate the ultraviolet stability of such cells, to develop concentrator cells based on n-type substrates, and to transfer technology to appropriate commercial environments. Key results include the identification of contact resistance between boron-defused areas and rear aluminum as the source of anomalously large series resistance in both p- and n-type cells. A major achievement of the present project was the successful transfer of cell technology to both Applied Solar Energy Corporation and Solarex Corporation.

  20. Photovoltaic concentrator initiative: Concentrator cell development

    SciTech Connect

    Wohlgemuth, J.H.; Narayanan, S.

    1993-05-01

    This project involves the development of a large-area, low-cost, high-efficiency concentrator solar cell for use in the Entech 22-sun linear-focus Fresnel lens concentrator system. The buried contact solar cell developed at the University of New South Wales was selected for this project. Both Entech and the University of New South Wales are subcontractors. This annual report presents the program efforts from November 1990 through December 1991, including the design of the cell, development of a baseline cell process, and presentation of the results of preliminary cell processing. Important results include a cell designed for operation in a real concentrator system and substitution of mechanical grooving for the previously utilized laser scribing.