Self-Efficacy for Therapeutic Mode Use among Occupational Therapy Students in Norway

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Opseth, Thea Moos; Carstensen, Tove; Yazdani, Farzaneh; Ellingham, Brian; Thørrisen, Mikkel Magnus; Bonsaksen, Tore

2017-01-01

Background: The intentional relationship model (IRM) proposes six distinct ways of relating to clients. A new instrument for measuring self-efficacy for using the therapeutic modes in occupational therapy practice was recently found to have good psychometric properties. To date, however, no research has investigated factors associated with…

Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent.

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Garay, Ricardo P; Chiavaroli, Carlo; Hannaert, Patrick

2006-01-01

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. This review covers more than 40 years of intensive clinical and fundamental research with ethamsylate. First, we summarize the large medical literature concerning its clinical efficacy. Of these, well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding. Second, we review the numerous investigations performed to elucidate the mechanism of action of ethamsylate. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. Recent studies showed that ethamsylate promotes P-selectin-dependent, platelet adhesive mechanisms. Finally, we compare ethamsylate with other recent hemostatic agents. It is suggested that the place of ethamsylate as a hemostatic agent is that of a mild but well-tolerated drug, particularly useful in dysfunctional uterine bleeding when contraception is not needed.

Therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia

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Ekta Atul Thakkar

2014-12-01

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

Shangri-La revisited: an exploration of therapeutic efficacy among intentional communities.

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Francis, T L

1992-04-01

Field and literature surveys were employed to explore the therapeutic efficacy of a reportedly common set of social structures found among some Intentional Communities (ICs). Substance misuse served as an example of social problems plausibly related to the examined social structures, which included: (1) meditative practices, (2) progressive education, (3) holistic health practices, (4) nutritional diet, (5) open policy making, (6) equally or equitably shared resources, (7) integrating membership processes, and (8) environmental concern. The field survey identified and examined 11 such ICs, and the literature exploration concerning the structures found that they appear to be therapeutic. Future research should focus on refining the study of structural and antecedent variables and on finding relationships between these variables to communities in the larger society.

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

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Sheng-Mou Hsiao

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

Therapeutic efficacy of uterine arterial embolization for intractable uterine hemorrhage

International Nuclear Information System (INIS)

Liu Lang; Lu Lianwei; Ke Mengjia; Zhao Ru'en; Zeng Shaolan

2010-01-01

Objective: To evaluate the therapeutic efficacy of uterine arterial embolization (UAE) for intractable uterine hemorrhage. Methods: 16 patients with intractable uterine hemorrhage underwent bilateral UAE after failed conventional conservative treatment. Results: Uterine hemorrhage ceased within 12 hours in 15 patients (93.8%) after bilateral super-selective UAE. Internal iliac artery embolization was performed on one patient (6.2%) and hysterectomy was eventually carried out because of recurrent hemorrhage. Conclusion: UAE is a rapid and effective treatment method obviating hysterectomy for intractable uterine hemorrhage. (authors)

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

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

2017-06-01

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

Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

DEFF Research Database (Denmark)

Gustafsson, Anna M E; Bäck, Tom; Elgqvist, Jörgen

2012-01-01

The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.......The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model....

Therapeutic efficacy of Artemether/Lumefantrine (Coartem® against Plasmodium falciparum in Kersa, South West Ethiopia

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Animut Abebe

2010-01-01

Full Text Available Abstract Background Artemether/Lumefantrine (Coartem® has been used as a first-line treatment for uncomplicated Plasmodium falciparum infection since 2004 in Ethiopia. In the present study the therapeutic efficacy of artemether/lumefantrine for the treatment of uncomplicated P. falciparum infection at Kersa, Jima zone, South-west Ethiopia, has been assessed. Methods A 28 day therapeutic efficacy study was conducted between November 2007 and January 2008, in accordance with the 2003 WHO guidelines. Outcomes were classified as early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Results 90 patients were enrolled and completed the 28 day follow-up period after treatment with artemether/lumefantrine. Cure rate was very high, 96.3%, with 95% CI of 0.897-0.992 (PCR uncorrected. Age-stratified data showed adequate clinical and parasitological response (ACPR to be 100% for children under 5 and 97.4% and 87.3% for children aged 5-14, and adults, respectively. There was no early treatment failure (ETF in all age groups. Fever was significantly cleared on day 3 (P 0.05. No major side effect was observed in the study except the occurrence of mouth ulcers in 7% of the patients. Conclusions The current study proved the excellent therapeutic efficacy of artemether/lumefantrine in the study area and the value of using it. However, the proper dispensing and absorption of the drug need to be emphasized in order to utilize the drug for a longer period of time. This study recommends further study on the toxicity of the drug with particular emphasis on the development of oral ulcers in children.

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

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Oh, Doo-Byoung

2015-08-01

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

The mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization

International Nuclear Information System (INIS)

Li Weiduo; Yang Jianyong; Zhuang Wenquan; Chen Wei; Li Heping

2002-01-01

Objective: To explore the mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization. Methods: Twenty-five patients of Graves' disease treated with interventional embolization were followed up for 24-57 months. T 3 and T 4 were monitored at pre-operation, six months, 12 months, 2, 3 and 4 years after operation, respectively. Other references included pulse, thyroid size, and vessel's murmur. Results: Twenty-two patients completely relieved from the hyperthyroidism during the follow-up. Only one patient suffered from recurrence. Other two patients were still on maintaining dosage of antithyroid drug therapy. No hypothyroidism or hypoparathyroidism was found during this term. Conclusion: Mid-to-long term follow-up showed satisfactory efficacy of interventional therapy, offering another alternative for treatment of refractory Graves' disease

Correlation between paclitaxel Tc > 0.05 and its therapeutic efficacy and severe toxicities in ovarian cancer patients

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Shuyao Zhang

2016-01-01

Conclusion: These results indicated that the PTX Tc > 0.05 correlated with therapeutic efficacy and drug toxicity. Therefore, monitoring the PTX Tc > 0.05 other than blood concentration of PTX is necessary to optimize individual treatment.

Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins

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Alison Smith

2016-01-01

Full Text Available Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.

New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

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Robert H E Friesen

2010-02-01

Full Text Available The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.

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

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Gallen Triana-Baltzer

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

Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.

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Salaam, Amanee D; Hwang, Patrick T J; Poonawalla, Aliza; Green, Hadiyah N; Jun, Ho-wook; Dean, Derrick

2014-10-24

Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.

Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

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Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Uesato, Shin-ichi [Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680 (Japan); Watanabe, Kazushi [Proubase Technology Inc., Kanagawa 211-0063 (Japan); Tanimura, Susumu [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Koji, Takehiko [Department of Histology and Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kohno, Michiaki, E-mail: kohnom@nagasaki-u.ac.jp [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Proubase Technology Inc., Kanagawa 211-0063 (Japan); Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501 (Japan)

2013-04-19

Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.

Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

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Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

2017-10-01

The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure

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Dickinson, Brent A; Semus, Hillary M; Montgomery, Rusty L; Stack, Christianna; Latimer, Paul A; Lewton, Steven M; Lynch, Joshua M; Hullinger, Thomas G; Seto, Anita G; van Rooij, Eva

AIMS: Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in

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

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Jeehoon Kang

2016-11-01

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

Adverse events and therapeutic efficacy associated with TACE for hepatocellular carcinoma with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension

International Nuclear Information System (INIS)

Araki, Takuji; Okada, Taiki; Kimura, Kazufumi; Sawada, Eiichi; Sano, Katushiro; Araki, Tsutomu

2012-01-01

The aim of this study was to evaluate the short-term adverse events and therapeutic efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension. Of patients who underwent TACE for unresectable HCCs in 2009 and 2010, twenty-nine and twenty-seven patients underwent TACE using cisplatin-lipiodol suspension (C-LS) and miriplatin-lipiodol suspension (M-LS), respectively. Adverse events of fever, pain, nausea, anorexia, elevation of aspartate aminotransferase (AST), total bilirubin, creatinine and a decrease in platelet count were evaluated by the National Cancer Institute Common Toxicity Criteria Ver.4. to compare the C-LS and M-LS groups. The short-term therapeutic efficacy of both groups was evaluated by the treatment effect (TE) on the CT images three months after TACE according to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer (the 5th edition, Revised Version). With regard to the adverse events, the M-LS group had significantly less fever and anorexia than the C-LS group. No critical adverse events were observed in either group. The therapeutic efficacy was not significantly different between the groups. TACE with M-LS had fewer adverse events than TACE with C-LS, but neither TACE led to any critical adverse events. The short-term therapeutic efficacy of TACE with M-LS was equivalent to that of TACE with C-LS. (author)

Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

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Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

2016-07-01

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells

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

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Safieh Mohebitabar

2017-04-01

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

Prevalence of Schistosoma mansoni infection and the therapeutic efficacy of praziquantel among school children in Manna District, Jimma Zone, southwest Ethiopia

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Mitiku Bajiro

2016-10-01

Full Text Available Abstract Background Intestinal schistosomiasis is one of the neglected tropical parasitic diseases caused by Schistosoma mansoni. Currently, the control measures for the disease are mainly based on mass drug administration (MDA with praziquantel (PZQ targeting the school-age children. In Ethiopia, the potential foci for schistosomiasis and therapeutic efficacy of PZQ among school-age children remain poorly explored. Therefore, we determined both the prevalence and intensity of S. mansoni infection and the therapeutic efficacy of PZQ among school children in the Manna District (new foci for S. mansoni, Jimma Zone, southwest Ethiopia. Methods A cross-sectional study was conducted among the school children aged between 6 and 18 years in three primary schools in Manna district from March to April 2014. For diagnosis of S. mansoni, a single stool sample was obtained from each child and processed using single Kato Katz and examined under light microscopy. A questionnaire was used to collect demographic information of the school children participated in the study. School children excreting eggs of S. mansoni were administered with 40 mg/kg of PZQ and re-examined after three weeks post-treatment. The therapeutic efficacy of PZQ against S. mansoni was evaluated by means of cure rate and egg reduction rate. Results The overall prevalence of S. mansoni among the school children in the three primary schools in Manna District was 24.0 %. Higher prevalence was recorded for males 25.6 % (61/238 than for females 22.5 % (59/262. Majority (27.5 % of infection intensity was light with mean faecal egg count (FEC of 202 eggs per gram (EPG. The therapeutic efficacy of PZQ at a dose of 40 mg/kg was highly efficient (cure rate of 99.1 % and egg reduction rate of 99.9 % among the school children in the three primary schools in Manna District. Conclusions The school children in the three primary schools of Manna District, Jimma Zone were at moderate risk of the

Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.

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Cameron P Simmons

2007-05-01

Full Text Available New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1 in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1. mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1.These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1

Recombinant proteins in therapeutics: haemophilia treatment as an example

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Liras Antonio

2008-04-01

Full Text Available Abstract One of the most spectacular advances in the history of scientific knowledge was the discovery of deoxyribonucleic acid (DNA by Watson and Crick in 1953. This enabled certain proteins to be prepared in this way for their therapeutic use in clinical practice. Today, in the first decade of the 21st century, hundreds of therapeutic proteins have been produced recombinantly and about 50 of them have been approved for clinical use. Because of the specific procedure used for obtaining these products, which is based on expressing a atherapeutica gene from a fragment of DNA in a cell to produce a functional protein that is free from any human or animal component, they are especially acleana and thus the therapy of choice for many current diseases. The immediate question is: why are recombinant products not used more extensively given their high efficacy and maximum safety? In short, we are faced with an interesting but also unfortunate paradox of pharmacology that greater progress in therapeutic procedures is not always associated with greater introduction of those resources that are safest, for the simple reason that they are more costly.

Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

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Zhang, Aihua; Sun, Hui; Wang, Xijun

2014-04-01

Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

Therapeutic efficacy of different brands of albendazole against soil transmitted helminths among students of Mendera Elementary School, Jimma, Southwest Ethiopia.

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Tefera, Ephrem; Belay, Tariku; Mekonnen, Seleshi Kebede; Zeynudin, Ahmed; Belachew, Tefera

2015-01-01

Different brands Albendazole are commercially available and the efficacious brand/s is/are required for effective control of STHs infection. Thus, this study is aimed at determining the therapeutic efficacy of different brands of albendazole against soil transmitted helminths among school children of Jimma town. A cross sectional survey for prevalence of geohelminths and a randomized trial for efficacy study of different brands of albendazole was conducted among students Mendera Elementary School from March 29 to April 29, 2010. Positive subjects were randomized into three treatment arms using lottery method. The collected stool samples were examined by the McMaster method. CRs were calculated using SPSS windows version 16 and ERRs were calculated using appropriate formula. Of the 715 school children who had their stools examined, 326 were positive for STHs with a prevalence rate of 45.6%. The cure rates (CR) for A. lumbricoides, T. trichiura and Hookworm were 99.4, 59.9 and 93.7%, respectively. Similarly, the egg reduction rates (ERR) were 97, 99.9 and 99.9% respectively. A statistical significant mean STH egg count difference were observed between pre and post-intervention study (p 0.05). All the three brands of Albendazole tested regardless of the brand type were therapeutically efficacious for Ascariasis, Trichuriasis and Hookworm infections irrespective of the infection status whether it was single or multiple.

Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

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Claudia P. Miller

2011-01-01

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

Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis.

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Pensel, Patricia E; Castro, Silvina; Allemandi, Daniel; Bruni, Sergio Sánchez; Palma, Santiago D; Elissondo, María Celina

2014-06-16

Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

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Stefano Salmaso

2013-01-01

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

Efficacy of escitalopram monotherapy in the treatment of major depressive disorder

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Li, Guanjun; Shen, Yifeng; Luo, Jianfeng; Li, Huafang

2017-01-01

Abstract This study aimed to evaluate the efficacy of escitalopram monotherapy in the treatment of major depressive disorder (MDD) on the basis of pooled data analysis of 4 Chinese clinical trials. A total of 649 outpatients with MDD score of ≥18 at the 17-item Hamilton Depression Rating Scale (HAMD17) were included across 4 eligible studies. Patients were treated with 10 mg/day escitalopram for 2 weeks, and then 20 mg/day escitalopram was administered if the clinical response was poor. The change in total HAMD17 score was significantly greater in moderate MDD group than in other subgroups (P Escitalopram monotherapy is effective and safe in the treatment of MDD in Chinese patients, and therapeutic efficacy is dependent on the severity of MDD. Further study is needed to identify better predictors of therapeutic responses. PMID:28953649

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

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D. W. Nigg

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

International Nuclear Information System (INIS)

Nigg, D.W.

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

Therapeutic Efficacy of Bipolar Radiofrequency Thermotherapy for Patients with Chronic Prostatitis: A Retrospective Analysis of 26 Cases

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Lim, Ju Young; Shim, Seung Bum; Yoo, Dong Hoon; Park, Young Woong; Kim, Jong Yeon; Noh, Joon Hwa

2012-01-01

Purpose Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. Materials and Methods A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 year...

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

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Gulati, Karan [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia); Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M. [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Atkins, Gerald J., E-mail: gerald.atkins@adelaide.edu.au [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Losic, Dusan, E-mail: dusan.losic@adelaide.edu.au [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia)

2016-12-01

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

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

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Tae-Hyun Kim

2014-01-01

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

Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

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Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

2013-05-01

Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

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

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Basanti Jena

2013-12-01

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

Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs

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Ildiko Barabasi

2016-11-01

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

The Therapeutic Efficacy of Domestic Violence Victim Interventions.

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

2016-04-01

A meta-analysis on domestic violence interventions was conducted to determine overall effectiveness of mental health programs involving women and children in joint treatment. These interventions were further analyzed to determine whether outcomes are differentially affected based on the outcome measure employed. To date, no meta-analyses have been published on domestic violence victim intervention efficacy. The 17 investigations that met study criteria yielded findings indicating that domestic violence interventions have a large effect size (d = .812), which decreases to a medium effect size when compared to control groups (d = .518). Effect sizes were assessed to determine whether treatment differed according to the focus of the outcome measure employed: (a) external stress (behavioral problems, aggression, or alcohol use); (b) psychological adjustment (depression, anxiety, or happiness); (c) self-concept (self-esteem, perceived competence, or internal locus of control); (d) social adjustment (popularity, loneliness, or cooperativeness); (e) family relations (mother-child relations, affection, or quality of interaction); and (f) maltreatment events (reoccurrence of violence, return to partner). Results reveal that domestic violence interventions across all outcome categories yield effects in the medium to large range for both internalized and externalized symptomatology. Implications for greater awareness and support for domestic violence treatment and programming are discussed. © The Author(s) 2015.

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

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

2010-02-01

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

Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

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Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

2010-01-15

Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

Introduction to current and future protein therapeutics: a protein engineering perspective.

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Carter, Paul J

2011-05-15

Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies to address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

Therapeutic Strategy for Chronic Headache in Children

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H.O. Lezhenko

2016-05-01

Full Text Available The therapeutic efficacy of a combined homeopathic preparation Cefavora, which consists of alcoholic extracts of Ginkgo biloba, hawthorn (Crataegus and white mistletoe (Viscum album, has been studied in the treatment of chronic tension-type headache in children. It has been shown that alongside with elimination of headache manifestations, the use of homeopathic medicine has contributed to the normalization of adaptive mechanisms of autonomic regulation in children indicating its high therapeutic efficacy.

Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

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Yuya Yoshimoto

Full Text Available PURPOSE: There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL activity. METHODS AND MATERIALS: C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD was defined as the time (in days for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days and prolonged median survival time (MST to 59 days (versus 28 days in the non-irradiated group. CD8(+ cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days. Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days, while anti-FR4 and anti-GITR antibodies did not affect efficacy. CONCLUSIONS: Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4

Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

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Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a

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

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V. V. Sokolov

2016-01-01

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

Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.

Science.gov (United States)

Svendsen, Torleiv; Brodtkorb, Eylert; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I; Johannessen Landmark, Cecilie

2017-07-01

Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.

Novel therapeutic uses and formulations of botulinum neurotoxins: a patent review (2012 - 2014).

Science.gov (United States)

Kane, Christopher D; Nuss, Jonathan E; Bavari, Sina

2015-06-01

Botulinum neurotoxins (BoNTs) are among the most toxic of known biological molecules and function as acetylcholine release inhibitors and neuromuscular blocking agents. Paradoxically, these properties also make them valuable therapeutic agents for the treatment of movement disorders, urological conditions and hypersecretory disorders. Greater understanding of their molecular mechanism of action and advances in protein engineering has led to significant efforts to improve and expand their function with a view towards broadening their therapeutic potential. Searches of Espacenet and Google Patent have revealed a number of patents related to BoNTs. This review will focus on novel therapeutic uses and formulations disclosed during 2012 - 2014. The seven patents discussed will include nanoformulations of FDA-approved BoNTs, additional BoNT subtypes and novel BoNT variants and chimeras created through protein engineering. Supporting patents and related publications are also briefly discussed. The clinical and commercial success of BoNTs has prompted investigation into novel BoNTs or BoNT-mediated chimeras with promising in vitro results. Distinct strategies including the use of nanoformulations and targeted delivery have been implemented to identify new indication and improved functionality. Greater understanding of their systemic exposure, efficacy and safety profiles will be required for further development.

Percutaneous Radiofrequency Ablation for the Hepatocellular Carcinoma Abutting the Diaphragm: Assessment of Safety and Therapeutic Efficacy

International Nuclear Information System (INIS)

Kang, Tae Wook; Rhim, Hyun Chul; Kim, Eun Young; Kim, Young Sun; Choi, Dong Il; Lee, Won Jae; Lim, Hyo K.

2009-01-01

To assess the safety and therapeutic efficacy of a percutaneous radiofrequency (RF) ablation for the hepatocellular carcinoma (HCC) abutting the diaphragm. We retrospectively assessed 80 patients who underwent a percutaneous RF ablation for a single nodular (< 4 cm) HCC over the last four years. Each patient underwent an ultrasound-guided RF ablation using internally cooled electrodes for the first-line treatment. We divided patients into two subgroups based on whether the index tumor was abutting (less than 5 mm) the diaphragm or not: group A (abutting; n = 31) versus group B (non-abutting; n = 49). We compared the two subgroups for complications and therapeutic efficacy using image and the review of medical records. The statistical assessment included an independent t-test, Fisher's exact test, and chi-square test. The assessment of the diaphragmatic swelling at CT immediately following the procedure was more severe in group A than group B (mean thickness change:1.44 vs. 0.46 mm, p = 0.00). Further, right shoulder pain was more common in group A than B (p = 0.01). Although minor complications (hemothorax 1 case, pleural effusion 1 case) were noted only in group A, no major thoracic complication occurred in either group. The technical success rate was lower in group A than group B (84% vs. 98%, p = 0.03). As well, the primary and secondary technique effectiveness rates in group A and group B were 90% versus 98% (p = 0.29) and 79% versus 91% (p = 0.25), respectively. The local tumor progression rate was higher in group A than in group B (29% vs. 6%, p = 0.02). We found that the percutaneous RF ablation for the HCC abutting the diaphragm is a safe procedure without major complications. However, it is less effective with regard to technical success and local tumor control

A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug.

Science.gov (United States)

Li, Jingwen; Lyv, Zhonglin; Li, Yanli; Liu, Huan; Wang, Jinkui; Zhan, Wenjun; Chen, Hong; Chen, Huabing; Li, Xinming

2015-05-01

Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic efficacy of ranitidine bismuth citrate with clarithromycin for seven days in the eradication of Helicobacter pylori in Brazilian peptic ulcer patients

Directory of Open Access Journals (Sweden)

Jaime Natan Eisig

Full Text Available CONTEXT: The curative treatment of peptic ulcer is made available nowadays through the eradication of the bacterium Helicobacter pylori, which is associated with it, but the best therapeutic regimen is yet to be determined. OBJECTIVE: To assess the efficacy of a therapeutic regimen with 400 mg ranitidine bismuth citrate associated with 500 mg clarithromycin given twice a day for seven days in a cohort of Brazilian patients with peptic ulcer. TYPE OF STUDY: Cross-sectional study. SETTING: Tertiary-care hospital. PATIENTS: One hundred and twenty nine outpatients, with active or healed peptic ulcers infected by Helicobacter pylori, diagnosed via endoscopy with confirmation via the urease test and histological examination, who had never undergone a regimen for the eradication of the bacterium. PROCEDURE: Administration of 400 mg ranitidine-bismuth and 500 mg clarithromycin twice a day, for seven days. MAIN MEASUREMENTS: Efficacy of the treatment, with a check on the cure done via another endoscopy eight weeks after drug administration. The eradication of the bacterium was determined via the urease test and histological examination. Patients who were negative for both were considered to be cured. RESULTS: Eight patients failed to complete the study. The eradication rate according to intention to treat was 81% (104/129 and per protocol was 86% (104/121. CONCLUSION: The bismuth ranitidine compound associated with clarithromycin used for one week was shown to be a simple, effective and well-tolerated therapeutic regimen for the eradication of Helicobacter pylori.

Therapeutic efficacy of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome.

Science.gov (United States)

Kajiwara, Mitsuru; Inoue, Shougo; Kobayashi, Kanao; Ohara, Shinya; Teishima, Jun; Matsubara, Akio

2014-04-01

Narrow band imaging cystoscopy can increase the visualization and detection of Hunner's lesions. A single-center, prospective clinical trial was carried out aiming to show the effectiveness of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome. A total of 23 patients (19 women and 4 men) diagnosed as having ulcer-type interstitial cystitis/painful bladder syndrome were included. All typical Hunner's lesions and suspected areas identified by narrow band imaging were electrocoagulated endoscopically after the biopsy of those lesions. Therapeutic efficacy was assessed prospectively by using visual analog scale score of pain, O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score. The mean follow-up period was 22 months. All patients (100%) experienced a substantial improvement in pain. The average visual analog scale pain scores significantly decreased from 7.3 preoperatively to 1.2 1 month postoperatively. A total of 21 patients (91.3%) who reported improvement had at least a 50% reduction in bladder pain, and five reported complete resolution. Daytime frequency was significantly decreased postoperatively. O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score were significantly decreased postoperatively. However, during the follow-up period, a total of six patients had recurrence, and repeat narrow band imaging-assisted transurethral electrocoagulation of the recurrent lesions was carried out for five of the six patients, with good response in relieving bladder pain. Our results showed that narrow band imaging-assisted transurethral electrocoagulation could be a valuable therapeutic alternative in patients with ulcer-type interstitial cystitis/painful bladder syndrome, with good efficacy and reduction of recurrence rate. © 2014 The Japanese Urological Association.

Therapeutic product disposition in at-risk populations

International Nuclear Information System (INIS)

Foster, B. C.

2009-01-01

In an emergency situation, such as a chemical, biological, radionuclide, nuclear or explosion (CBRNE) event, all patient populations are at increased risk of serious adverse events. Therapeutic product (TP) safety and efficacy depend on the disposition of the product through absorption, distribution, metabolism and excretion. The ability of a patient to benefit from or merely tolerate a TP can be modified by many factors, including but not limited to culture, diet, disease, environmental contaminants, genetic predisposition, stress and socioeconomic status and recent life experiences. Metabolism is considered to have the greatest effect on safety and efficacy, as chemicals not metabolised can accumulate to toxic levels. Inter-individual variances in most drug metabolism enzymes may range up to greater than 1000-fold. The fetus, neonates, infants, individuals with hormonal change, infection or prior exposure to licit or illicit products and the elderly are more susceptible to increased risk of serious adverse health effects. The critically ill are the most at risk. The at-risk populations for a serious adverse event are dependent then on the CBRNE event, their physical and cognitive states and the inter-individual intrinsic and extrinsic factors that affect TP disposition. (authors)

Therapeutic Cancer Vaccines in Combination with Conventional Therapy

DEFF Research Database (Denmark)

Andersen, Mads Hald; Junker, N.; Ellebaek, E.

2010-01-01

The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

Therapeutic cancer vaccines in combination with conventional therapy

DEFF Research Database (Denmark)

Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

2010-01-01

The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

Therapeutic cloning in individual parkinsonian mice

Science.gov (United States)

Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

Structuring polymers for delivery of DNA-based therapeutics: updated insights.

Science.gov (United States)

Gupta, Madhu; Tiwari, Shailja; Vyas, Suresh

2012-01-01

Gene therapy offers greater opportunities for treating numerous incurable diseases from genetic disorders, infections, and cancer. However, development of appropriate delivery systems could be one of the most important factors to overcome numerous biological barriers for delivery of various therapeutic molecules. A number of nonviral polymer-mediated vectors have been developed for DNA delivery and offer the potential to surmount the associated problems of their viral counterpart. To address the concerns associated with safety issues, a wide range of polymeric vectors are available and have been utilized successfully to deliver their therapeutics in vivo. Today's research is mainly focused on the various natural or synthetic polymer-based delivery carriers that protect the DNA molecule from degradation, which offer specific targeting to the desired cells after systemic administration, have transfection efficiencies equivalent to virus-mediated gene delivery, and have long-term gene expression through sustained-release mechanisms. This review explores an updated overview of different nonviral polymeric delivery system for delivery of DNA-based therapeutics. These polymeric carriers have been evaluated in vitro and in vivo and are being utilized in various stages of clinical evaluation. Continued research and understanding of the principles of polymer-based gene delivery systems will enable us to develop new and efficient delivery systems for the delivery of DNA-based therapeutics to achieve the goal of efficacious and specific gene therapy for a vast array of clinical disorders as the therapeutic solutions of tomorrow.

Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

Science.gov (United States)

Zhang, Yaxiong; Zhang, Zhonghan; Huang, Xiaodan; Kang, Shiyang; Chen, Gang; Wu, Manli; Miao, Siyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

2017-09-01

Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib). Copyright © 2016 Elsevier Inc. All rights reserved.

Gut microbiota modulation of chemotherapy efficacy and toxicity.

Science.gov (United States)

Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

2017-06-01

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

The Novel IκB Kinase β Inhibitor, IMD-0560, Has Potent Therapeutic Efficacy in Ovarian Cancer Xenograft Model Mice.

Science.gov (United States)

Sawada, Ikuko; Hashimoto, Kae; Sawada, Kenjiro; Kinose, Yasuto; Nakamura, Koji; Toda, Aska; Nakatsuka, Erika; Yoshimura, Akihiko; Mabuchi, Seiji; Fujikawa, Tomoyuki; Itai, Akiko; Kimura, Tadashi

2016-05-01

Aberrant activation of nuclear factor-kappa β (NF-κB) signaling has been correlated with poor outcome among patients with ovarian cancer. Although the therapeutic potential of NF-κB pathway disruption in cancers has been extensively studied, most classical NF-κB inhibitors are poorly selective, exhibit off-target effects, and have failed to be applied in clinical use. IMD-0560, N-[2,5-bis (trifluoromethyl) phenyl]-5-bromo-2-hydroxybenzamide, is a novel low-molecular-weight compound that selectively inhibits the IκB kinase complex and works as an inhibitor of NF-κB signaling. The aim of this study was to assess the therapeutic potential of IMD-0560 against ovarian cancer in vitro and in vivo. NF-κB activity (phosphorylation) was determined in 9 ovarian cancer cell lines and the inhibitory effect of IMD-0560 on NF-κB activation was analyzed by Western blotting. Cell viability, cell cycle, vascular endothelial growth factor (VEGF) expression, and angiogenesis were assessed in vitro to evaluate the effect of IMD-0560 on ovarian cancer cells. In vivo efficacy of IMD-0560 was also investigated using an ovarian cancer xenograft mouse model. The NF-κB signaling pathway was constitutively activated in 8 of 9 ovarian cancer cell lines. IMD-0560 inhibited NF-κB activation and suppressed ovarian cancer cell proliferation by inducing G1 phase arrest. IMD-0560 decreased VEGF secretion from cancer cells and inhibited the tube formation of human umbilical vein endothelial cells. IMD-0560 significantly inhibited peritoneal metastasis and prolonged the survival in an ovarian cancer xenograft mice model. Immunohistochemical staining of excised tumors revealed that IMD-0560 suppressed VEGF expression, tumor angiogenesis, and cancer cell proliferation. IMD-0560 showed promising therapeutic efficacy against ovarian cancer xenograft mice by inducing cell cycle arrest and suppressing VEGF production from cancer cells. IMD-0560 may be a potential future option in regimens for the

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

Directory of Open Access Journals (Sweden)

Danbo Yang

2010-12-01

Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

International Nuclear Information System (INIS)

Yang, Danbo; Yu, Lei; Van, Sang

2010-01-01

The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

Energy Technology Data Exchange (ETDEWEB)

Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

2010-12-23

The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-03-15

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

Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

Science.gov (United States)

Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

2015-01-01

Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

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

OpenAIRE

Thomas L. Chenevert; Charles R. Meyer; Bradford A. Moffat; Alnawaz Rehemtulla; Suresh K. Mukherji; Stephen S. Gebarski; Douglas J. Quint; Patricia L. Robertson; Theodore S. Lawrence; Larry Junck; Jeremy M. G. Taylor; Timothy D. Johnson; Qian Dong; Karin M. Muraszko; James A. Brunberg

2002-01-01

The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular ...

Perceived collective teacher efficacy in low performing schools

African Journals Online (AJOL)

Education Management and Leadership, School for Professional Studies in ... enhance collective teacher efficacy, the challenge of low-performing schools ... Collective teacher efficacy, therefore, involves the combined perceptions of ... because greater efficacy leads to greater effort and ... One of the strategies for sharing.

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

Science.gov (United States)

Bradbury, Allison M; Gray-Edwards, Heather L; Shirley, Jamie L; McCurdy, Victoria J; Colaco, Alexandria N; Randle, Ashley N; Christopherson, Pete W; Bird, Allison C; Johnson, Aime K; Wilson, Diane U; Hudson, Judith A; De Pompa, Nicholas L; Sorjonen, Donald C; Brunson, Brandon L; Jeyakumar, Mylvaganam; Platt, Frances M; Baker, Henry J; Cox, Nancy R; Sena-Esteves, Miguel; Martin, Douglas R

2014-01-01

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated GM2 patients and those in future clinical trials. PMID:25284324

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

Science.gov (United States)

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

2017-01-01

The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children ( n = 8) and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological comorbidity; children with intellectual impairment were excluded (IQ Stress Index, Beck Depression Inventory, Children's Depression Inventory, and Revised Children's Manifest Anxiety Scale) at pre- and post-intervention, and administered satisfaction surveys following the intervention. Participants' opinions about the program's necessity, contents, and process, and participants' overall program satisfaction were analyzed. Parents and children reported high levels of satisfaction with the program. Externalizing behavioral problems, anxiety/depression, and emotional functioning from quality of life showed improvement after the intervention. Although not statistically significant, total child stress trended downward from pre- to post-intervention. A four-session structured therapeutic psycho-educational program for children and adolescents with chronic neurological illness and their parents was successfully implemented, showing good compliance and high satisfaction and efficacy.

Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease Is Phase Specific: Implication of its Therapeutic Effectiveness

Science.gov (United States)

Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara

2014-01-01

Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331

Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

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Olver, Mark E.; Wong, Stephen C. P.

2009-01-01

The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

The therapeutic efficacy of sacroiliac joint blocks with triamcinolone acetonide in the treatment of sacroiliac joint dysfunction without spondyloarthropathy.

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Liliang, Po-Chou; Lu, Kang; Weng, Hui-Ching; Liang, Cheng-Loong; Tsai, Yu-Duan; Chen, Han-Jung

2009-04-20

Prospective case series. The study aimed to investigate the therapeutic efficacy of sacroiliac joint (SIJ) blocks with triamcinolone acetonide in patients with SIJ pain without spondyloarthropathy. Numerous studies have demonstrated that SIJ blocks with corticosteroid/anesthetic provide long-term pain relief in seronegative spondyloarthropathy. However, only one report on SIJ dysfunction patients without spondyloarthropathy shows promising results. We conducted a prospective observational study of patients at a University Spine Center from March 2005 to May 2006. The above mentioned SIJ blocks were performed in 150 patients, and dual SIJ blocks confirmed SIJ pain in 39 patients (26%). Twenty-six patients (66.7%) experienced significant pain reduction for more than 6 weeks; the overall mean duration of pain reduction in these responders was 36.8 +/- 9.9 weeks. SIJ blocks were ineffective in 13 patients (33.3%); the mean duration of pain reduction in these patients was 4.4 +/- 1.8 weeks. Univariate analysis revealed that treatment failure was significantly associated with a history of lumbar/lumbosacral fusion (P = 0.03). SIJ blocks with triamcinolone acetonide are beneficial for some patients with SIJ pain without spondyloarthropathy. The SIJ blocks showed a long-lasting efficacy in two-thirds of the patients; however, the duration of its efficacy was shorter in patients with a history of lumbar/lumbosacral fusion. These findings suggest the need for further studies.

Therapeutic monoclonal antibody N-glycosylation - Structure, function and therapeutic potential.

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Cymer, Florian; Beck, Hermann; Rohde, Adelheid; Reusch, Dietmar

2018-03-01

Therapeutic antibodies (IgG-type) contain several post-translational modifications (PTMs) whereby introducing a large heterogeneity, both structural and functional, into this class of therapeutics. Of these modifications, glycosylation in the fragment crystallizable (Fc) region is the most heterogeneous PTM, which can affect the stability of the molecule and interactions with Fc-receptors in vivo. Hence, the glycoform distribution can affect the mode of action and have implications for bioactivity, safety and efficacy of the drug. Main topics of the manuscript include: What factors influence the (Fc) glycan pattern in therapeutic antibodies and how can these glycans be characterized? How does structure of the Fc-glycan relate to function and what methods are available to characterize those functions? Although heterogeneous in their scope, the different sections are intended to combine current knowledge on structure-function correlations of IgG glycan structures with regard to Fc (effector) functions, as well as basic aspects and methodologies for their assessment. Copyright © 2017. Published by Elsevier Ltd.

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

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

2017-05-01

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

Therapeutic Efficacy of Intermittent Cryotherapy in the Management ...

African Journals Online (AJOL)

This study was therefore, designed to investigate the efficacy of intermittent cryotherapy in the management of pain among human subjects who sustained closed soft tissue injuries (CSTIs). Subjects' pre- and post-treatment pain perception scores (PPS) using visual analogue scale (VAS) and the sessions of treatment were ...

Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

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Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

2008-06-01

Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

International Nuclear Information System (INIS)

Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

2008-01-01

Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

TC > 0.05 as a Pharmacokinetic Parameter of Paclitaxel for Therapeutic Efficacy and Toxicity in Cancer Patients.

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Xin, D S; Zhou, L; Li, C Z; Zhang, S Q; Huang, H Q; Qiu, G D; Lin, L F; She, Y Q; Zheng, J T; Chen, C; Fang, L; Chen, Zhe-Sheng; Zhang, S Y

2018-03-05

Paclitaxel (PTX) has remarkable anti-tumor activity, but it causes severe toxicities. There is an urgent need to seek an appropriate pharmacokinetic parameter of PTX to improve treatment efficacy and reduce adverse effects. To evaluate the association of pharmacokinetic parameter TC>0.05 of paclitaxel (PTX) and its therapeutic efficacy and toxicity in patients with solid tumors. A total of 295 patients with ovarian cancer, esophageal cancer, breast cancer, and non-small cell lung cancer (NSCLC), who were admitted to the Tumor Hospital of Shantou University Medical College, China, were recruited for this study. Patients received 3 weeks of PTX chemotherapy. The plasma concentrations of PTX were examined using the MyPaclitaxelTM kit. The patients' PTX TC>0.05 (the time during which PTX plasma concentration exceed 0.05 μmol/L) were calculated based on pharmacokinetic analysis. The results showed that: (1) the concentrations of PTX in these 295 patients ranged from 0.0358-0.127 μmol/L; (2) the PTX TC> 0.05 ranged from 14 to 38 h with a median time of 27 h; (3) among all treatment cycles, there was a statistically significant difference in the PTX TC>0.05 between CR+PR and SD+PD; (4) with the increasing value of TC>0.05, level of leukopenia and leukopenic fever increased; (5) high PTX TC>0.05 led to the occurrence of neutropenia, neutropenic fever, severe anemia, and severe peripheral neurotoxicity. Taken together, our results indicated that the pharmacokinetic parameter PTX TC>0.05 was an effective measure of treatment efficacy and toxicity in patients with solid tumors. Maintaining PTX TC>0.05 at 26 to 30 h could improve its efficacy and reduce the incidence of leukopenia, neutropenia, anemia, and peripheral neurotoxicity in these patients. PTX TC>0.05 is a key pharmacokinetic parameter of PTX which should be monitored to optimize individual treatment in patients with solid tumors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics

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Krakstad Camilla

2010-06-01

Full Text Available Abstract Glioblastoma multiforme (GBM is the most common primary brain tumour in adults and one of the most aggressive cancers in man. Despite technological advances in surgical management, combined regimens of radiotherapy with new generation chemotherapy, the median survival for these patients is 14.6 months. This is largely due to a highly deregulated tumour genome with opportunistic deletion of tumour suppressor genes, amplification and/or mutational hyper-activation of receptor tyrosine kinase receptors. The net result of these genetic changes is augmented survival pathways and systematic defects in the apoptosis signalling machinery. The only randomised, controlled phase II trial conducted targeting the epidermal growth factor receptor (EGFR signalling with the small molecule inhibitor, erlotinib, has showed no therapeutic benefit. Survival signalling and apoptosis resistance in GBMs can be viewed as two sides of the same coin. Targeting increased survival is unlikely to be efficacious without at the same time targeting apoptosis resistance. We have critically reviewed the literature regarding survival and apoptosis signalling in GBM, and highlighted experimental, preclinical and recent clinical trials attempting to target these pathways. Combined therapies simultaneously targeting apoptosis and survival signalling defects might shift the balance from tumour growth stasis to cytotoxic therapeutic responses that might be associated with greater therapeutic benefits.

Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

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Xiujuan Zhang

Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

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

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Thomas L. Chenevert

2002-10-01

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

Understanding music’s therapeutic efficacy: Implications for music education

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Diane Thram

2014-11-01

Full Text Available In the current era of electronic domination of human experience, be it via cell phone and/or computer addiction, or the ubiquitous television, actual participation in music- making is less and less common for the average person, child or adult. Passive participation through listening is most often cited by people as their major experience with music in their lives. When asked if listening has therapeutic effects, it is rare for anyone to respond in the negative. Likewise, for performers/active participants in music- making, be it solitary or as part of a group, invariably an enhanced sense of well-being from the act of making music is reported. This paper addresses therapeutic aspects of musical participation (singing, clapping, playing an instrument, dancing, listening by providing a historical overview (12th c to present of attitudes toward music’s therapeutic effects. It argues that music exists through the interaction of our biological capacity to make music with our cultural circumstances. How individuals benefit in all aspects their being – physical, mental and emotional – from engaging in the act of making music is illustrated with examples from field research in southern Africa. Finally implications for Music Education are explored which emphasize how more comprehensive integration of music into the curriculum can serve as an antidote to the increasing isolation and alienation of modern life.

A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

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Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

2018-03-20

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

Towards the therapeutic use of vascular smooth muscle progenitor cells.

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Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

2012-07-15

Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope

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Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R.; Gambhir, Sanjiv S.; Kino, Gordon S.; Solgaard, Olav; Kaspar, Roger L.; Contag, Christopher H.

2010-05-01

Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

Psychedelics and hypnosis: Commonalities and therapeutic implications.

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Lemercier, Clément E; Terhune, Devin B

2018-06-01

Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention. Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy. We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes. Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.

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

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Kostov Rostislav V

2015-07-01

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

Therapeutic efficacy and toxicity of a single and double application of boron neutron capture therapy (BNCT) in a hamster cheek pouch oral precancer model

International Nuclear Information System (INIS)

Monti Hughes, A; Pozzi, E C C; Thorp, S; Garabalino, M A; Farias, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Molinari, A J; Miller, M; Nigg, D W; Curotto, P; Trivillin, V A; Schwint, A E

2012-01-01

Tumor development from tissue with potentially malignant disorders (PMD) gives rise to second primary tumors. We previously demonstrated the partial inhibitory effect on tumor development of Boron Neutron Capture Therapy (BNCT) mediated by the boron compounds BPA (boronophenylalanine) and decahydrodecaborate (GB-10) in a hamster pouch oral precancer model. Seeking to optimize BNCT, the aim of the present study was to contribute to the knowledge of BNCT radiobiology for oral precancer and assess new BNCT protocols in terms of inhibition of tumor development and radiotoxicity. Groups of cancerized hamsters were locally exposed to single or double applications (2 weeks apart) of BPA-BNCT or (GB-10 + BPA)-BNCT at a total dose of 8Gy to tissue with PMD; to a single application of BPA-BNCT at 6Gy and to a double application (4 weeks apart) of BPA-BNCT or (BPA + GB-10)-BNCT at a total dose of 10Gy. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumor development from tissue with PMD and mucositis were followed for 8 months. The marked therapeutic efficacy of single applications of BNCT at 6 and 8Gy were associated to severe radiotoxicity. Dose fractionation into 2 applications reduced mucositis but also reduced therapeutic efficacy, depending on dose and interval between applications. A double application (4 weeks apart) of (GB-10 + BPA)-BNCT at a total dose of 10Gy rendered the best therapeutic advantage, i.e. 63% - 100% inhibition of tumor development with only slight mucositis in 67% of cases. The data reported herein show that issues such as dose levels and dose fractionation, interval between applications, and choice of boron compounds are pivotal to therapeutic advantage and must be tailored for a particular pathology and anatomic site. The present study determined treatment conditions that would contribute to optimize BNCT for precancer and that would warrant cautious assessment in a clinical scenario (author)

A Potent In Vivo Antitumor Efficacy of Novel Recombinant Type I Interferon.

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Zhang, Kang-Jian; Yin, Xiao-Fei; Yang, Yuan-Qin; Li, Hui-Ling; Xu, Yan-Ni; Chen, Lie-Yang; Liu, Xi-Jun; Yuan, Su-Jing; Fang, Xian-Long; Xiao, Jing; Wu, Shuai; Xu, Hai-Neng; Chu, Liang; Katlinski, Kanstantsin V; Katlinskaya, Yuliya V; Guo, Rong-Bing; Wei, Guang-Wen; Wang, Da-Cheng; Liu, Xin-Yuan; Fuchs, Serge Y

2017-04-15

Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I. Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK-STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models. Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK-STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8 + T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice. Conclusions: These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038-49. ©2016 AACR . ©2016 American Association for Cancer Research.

Therapeutic efficacy of chemotherapy with ACNU and radiation therapy for malignant glioma in the cerebral hemisphere

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Miyagami, Mitsusuke; Katayama, Yoichi; Nakamura, Saburo [Nihon Univ., Tokyo (Japan). School of Medicine

2000-10-01

Seventy-two patients with malignant gliomas (57 with glioblastoma and 15 with anaplastic astrocytoma) in the cerebral hemisphere were studied retrospectively to evaluate the therapeutic efficacy of chemotherapy with nimustine and radiation after surgery. Survival was analyzed with the Kaplan-Meier method in 21 patients treated with radiotherapy after surgery and 51 patients treated with nimustine and radiotherapy after surgery. Histological classification age, and the extent of resection of the tumors were significantly correlated with survival. The median survival time was 8 months in patients treated with radiotherapy and 15 months in patients treated with nimustine and radiotherapy. The 2- and 5-year survival rates were 12% and 0% in patients treated with radiotherapy and 33% and 22% in patients treated with nimustine and radiotherapy. Thus, a significant difference in survival was recognized, and chemotherapy with nimustine was found to be useful as an adjuvant therapy for glioblastoma after surgery. However, survival time did not differ between intravenous and intra-arterial infusion of nimustine. (author)

Therapeutic efficacy of hydro-kinesiotherapy Programs in lumbar spondylosis

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Ana-Maria BOTEZAN

2015-12-01

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

Efficacy of combination of glycolic acid peeling with topical regimen in treatment of melasma.

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Chaudhary, Savita; Dayal, Surabhi

2013-10-01

Various treatment modalities are available for management of melasma, ranging from topical and oral to chemical peeling, but none is promising alone. Very few studies are available regarding efficacy of combination of topical treatment with chemical peeling. Combination of chemical peeling and topical regimen can be a good treatment modality in the management of this recalcitrant disorder. To assess the efficacy of combination of topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling in the treatment of melasma in Indian patients. Forty Indian patients of moderate to severe epidermal variety melasma were divided into two groups of 20 each. One Group i.e. peel group received topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling and other group i.e. control group received topical regimen (2% hydroquinone, 1% hydrocortisone, 0.05% tretinoin). There was an overall decrease in MASI from baseline in 24 weeks of therapy in both the groups (P value peel with topical regimen showed early and greater improvement than the group which was receiving topical regimen only. This study concluded that combining topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling significantly enhances the therapeutic efficacy of glycolic acid peeling. The combination of glycolic acid peeling with the topical regimen is a highly effective, safe and promising therapeutic option in treatment of melasma.

Ultrasound-Guided Intermediate Site Greater Occipital Nerve Infiltration: A Technical Feasibility Study.

Science.gov (United States)

Zipfel, Jonathan; Kastler, Adrian; Tatu, Laurent; Behr, Julien; Kechidi, Rachid; Kastler, Bruno

2016-01-01

Two studies recently reported that computed tomography (CT) guided infiltration of the greater occipital nerve at its intermediate site allows a high efficacy rate with long-lasting pain relief following procedure in occipital neuralgia and in various craniofacial pain syndromes. The purpose of our study was to evaluate the technical feasibility and safety of ultrasound-guided intermediate site greater occipital nerve infiltration. Retrospective study. This study was conducted at the imaging department of a 1,409 bed university hospital. Local institutional review board approval was obtained and written consent was waived. In this retrospective study, 12 patients suffering from refractory occipital neuralgia or craniofacial pain syndromes were included between April and October 2014. They underwent a total of 21 ultrasound-guided infiltrations. Infiltration of the greater occipital nerve was performed at the intermediate site of the greater occipital nerve, at its first bend between obliqus capitis inferior and semispinalis capitis muscles with local anestetics and cortivazol. Technical success was defined as satisfactory diffusion of added iodinated contrast media in the fatty space between these muscles depicted on control CT scan. We also reported first data of immediate block test efficacy and initial clinical efficacy at 7 days, one month, and 3 months, defined by a decrease of at least 50% of visual analog scale (VAS) scores. Technical success rate was 95.24%. Patients suffered from right unilateral occipital neuralgia in 3 cases, left unilateral occipital neuralgia in 2 cases, bilateral occipital neuralgia in 2 cases, migraine in one case, cervicogenic headache in one case, tension-type headache in 2 cases, and cluster headache in one case. Block test efficacy was found in 93.3% (14/15) cases. Clinical efficacy was found in 80% of cases at 7 days, in 66.7% of cases at one month and in 60% of cases at 3 months. No major complications were noted. Some of the

Efficacy of therapeutic ultrasound and exercise therapy in the ...

African Journals Online (AJOL)

Results: Findings of the study revealed no significant difference in VAS, ROM and WOMAC scores in the study and control groups. Conclusions: This study confirms that therapeutic ultrasound is of no additional benefit to exercise therapy in the management of chronic osteoarthritis. Key words: Ultrasound; Exercise; ...

Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

Energy Technology Data Exchange (ETDEWEB)

Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)

2011-01-15

Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

Therapeutic drug monitoring of aminoglycosides in neonates

NARCIS (Netherlands)

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

2009-01-01

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

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

Directory of Open Access Journals (Sweden)

Anne Kleijn

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

Efficacy of a therapeutic vaccine using mutated β-amyloid sensitized dendritic cells in Alzheimer's mice.

Science.gov (United States)

Luo, Zhongqiu; Li, Jialin; Nabar, Neel R; Lin, Xiaoyang; Bai, Ge; Cai, Jianfeng; Zhou, Shu-Feng; Cao, Chuanhai; Wang, Jinhuan

2012-09-01

Despite FDA suspension of Elan's AN-1792 amyloid beta (Aβ) vaccine in phase IIb clinical trials, the implications of this study are the guiding principles for contemporary anti-Aβ immunotherapy against Alzheimer's disease (AD). AN-1792 showed promising results with regards to Aβ clearance and cognitive function improvement, but also exhibited an increased risk of Th1 mediated meningoencephalitis. As such, vaccine development has continued with an emphasis on eliciting a notable anti-Aβ antibody titer, while avoiding the unwanted Th1 pro-inflammatory response. Previously, we published the first report of an Aβ sensitized dendritic cell vaccine as a therapeutic treatment for AD in BALB/c mice. Our vaccine elicited an anti-Aβ titer, with indications that a Th1 response was not present. This study is the first to investigate the efficacy and safety of our dendritic cell vaccine for the prevention of AD in transgenic mouse models (PDAPP) for AD. We also used Immunohistochemistry to characterize the involvement of LXR, ABCA1, and CD45 in order to gain insight into the potential mechanisms through which this vaccine may provide benefit. The results indicate that (1) the use of mutant Aβ1-42 sensitized dendritic cell vaccine results in durable antibody production, (2) the vaccine provides significant benefits with regards to cognitive function without the global (Th1) inflammation seen in prior Aβ vaccines, (3) histological studies showed an overall decrease in Aβ burden, with an increase in LXR, ABCA1, and CD45, and (4) the beneficial results of our DC vaccine may be due to the LXR/ABCA1 pathway. In the future, mutant Aβ sensitized dendritic cell vaccines could be an efficacious and safe method for the prevention or treatment of AD that circumvents problems associated with traditional anti-Aβ vaccines.

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

Directory of Open Access Journals (Sweden)

Pushpa Gnanaraj

2011-01-01

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

Challenges of therapeutic substitution of drugs for economic reasons: focus on CVD prevention.

Science.gov (United States)

Johnston, Atholl

2010-04-01

Healthcare systems throughout the world are under increasing pressure to control and minimise costs. The substitution of initially-prescribed drugs with cheaper equivalents is an obvious option which presents a rapid and visible means to reduce these costs. Whether the substitution improves patient and/or population outcomes must be appraised and this paper highlights the conditions under which therapeutic substitution may require additional thought and consideration. In this paper, some of the medical evidence and the regulatory environment for and against the three types of therapeutic substitution - generic, within-class and between-class - are discussed. This article is not an exhaustive review of the literature, but captures some of the key clinical, pharmacological, economic, policy and ethical issues regarding generic and therapeutic substitution. Search criteria of the most commonly used terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence, were applied to Embase, PubMed and Google Scholar to identify relevant publications. Although population studies support therapeutic substitution in principle, there is evidence that substitution may not always result in therapeutic equivalence in individual patients, with the consequent potential for greater risks of decreased efficacy and/or increased safety concerns. Factors such as patient choice and therapeutic equivalence also play an important role in the effectiveness of the treatment and overall management of the patient. The pan-European regulatory environment provides another contradiction, encouraging widespread cost containment through reduction in drug acquisition costs, while simultaneously promoting an increased role for patients in defining and managing their own treatment. There is a strong rationale for careful management in some patients with cardiovascular disease. Treatment decisions should be transparent and based on strong clinical evidence. If not, drug substitution on

Design of clinical trials for therapeutic cancer vaccines development.

Science.gov (United States)

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

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

International Nuclear Information System (INIS)

Dudau, Cristina; Salim, Fakhruddin; Jiang, Dan; Connor, Steve E.J.

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-03-15

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

Evaluation of the safety and efficacy of therapeutic bandage contact lenses on post-cataract surgery patients.

Science.gov (United States)

Shi, Dan-Na; Song, Hang; Ding, Tong; Qiu, Wei-Qiang; Wang, Wei

2018-01-01

To evaluate the safety of therapeutic bandage contact lens for post-cataract surgery patients and to illustrate its efficacy on post-operative comfort and tear-film stability. A total of 40 participants were recruited and randomly divided into two groups. Group one was instructed to wear bandage contact lenses for a week and use antibiotic eye drops for a month since the first day after surgery. Group two received sub-conjunctival injection of tobramycin and was asked to wear eye pads on the first day after surgery and then were instructed to use antibiotic eye drops as the first group did. Ocular surface disease index (OSDI) questionnaire, slit-lamp microscope examination of tear break-up time (TBUT), corneal fluorescein score (CFS), tear meniscus height (TMH) together with anterior segment optical coherence tomography (AS-OCT) and corneal topography were evaluated preoperatively and postoperatively. The subjective feeling ( P =0.004), TBUT ( P <0.001) and TMH ( P =0.02) post-surgery had improved in patients who used bandage contact lenses compared with those who did not at 1wk post-surgery. Until three month postoperatively, the comfort degree ( P =0.004) and TMH ( P =0.01) of group two were still worse than group one. Moreover, TBUT ( P <0.001) and CFS ( P =0.004) of the group with eye pads got worse than the results before, whereas the group with bandage contact lenses recovered to normal. None of these patients had infections or other complications. Wearing therapeutic bandage contact lens after cataract surgery, compared with traditional eye-pads, is a safe method to improve tear-film stability and reduce post-operative discomfort without hindering corneal incision recovery.

Outcome results of self-efficacy in children with sickle disease pain who were trained to use guided imagery.

Science.gov (United States)

Dobson, Cassandra

2015-11-01

The aim of this study was to describe self-efficacy as a theoretical component of behavior change in various therapeutic treatments such as the management of SCD pain. The participants were prepared to self-initiate the GI for 5 to 10 minutes three times each day regardless of pain and also during each pain episode. As part of the GI training a tape or CD with guided imagery messages was provided. Participants were monitored for 4 weeks pre and 4 weeks post intervention (GI training). Children kept a daily record of pain episodes. During this time, children continued to record as before in their personal study diary: pain episodes (intensity and treatment), school attendance, and also the frequency of GI use. At the conclusion of this 4-week period, usual pain patterns (PAT), visual imagery ability (KIAQ), and disease specific self-efficacy scale were measured again. The Sickle Cell Self-Efficacy Scale (SCSES) is a new nine-item scale measuring disease-specific perceptions of self-efficacy. The instrument's developers established internal consistency by Cronbach's alpha of 0.89. H1: Children with SCD who are trained in guided imagery will have greater disease-specific self-efficacy following the training than they had prior to learning guided imagery; the hypothesis was tested and supported using t-tests of mean interval-level scores on the SCSES. Eighteen children had positive gained scores and sixteen children raised their scores more than one standard deviation above the mean score for this sample distribution. Greater self-efficacy scores are associated with better physical and psychological functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Key factors which concur to the correct therapeutic evaluation of herbal products in free radical-induced diseases.

Directory of Open Access Journals (Sweden)

Cesare eMancuso

2015-04-01

Full Text Available For many years now the world's scientific literature has been perfused with articles on the therapeutic potential of natural products, the vast majority of which have herbal origins, as in the case of free radical-induced diseases. What is often overlooked is the effort of researchers who take into consideration the preclinical and clinical evaluation of these herbal products, in order to demonstrate the therapeutic efficacy and safety. The first critical issue to be addressed in the early stages of the preclinical studies is related to pharmacokinetics, which is sometimes not very favorable, of some of these products, which limits the bioavailability after oral intake. In this regard, it is worthy underlining how it is often unethical to propose the therapeutic efficacy of a compound on the basis of preclinical results obtained with far higher concentrations to those which, hopefully, could be achieved in organs and tissues of subjects taking these products by mouth. The most widely used approach to overcome the problem related to the low bioavailability involves the complexation of the active ingredients of herbal products with non-toxic carriers that facilitate the absorption and distribution. Even the induction or inhibition of drug metabolizing enzymes by herbal products, and the consequent variations of plasma concentrations of co-administered drugs, are phenomena to be carefully evaluated as they can give rise to side-effects. This risk is even greater when considering that people lack the perception of the risk arising from an over use of herbal products that, by their very nature, are considered risk-free.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Directory of Open Access Journals (Sweden)

Mario Gimona

2017-06-01

Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

Do ABO blood group antigens hamper the therapeutic efficacy of mesenchymal stromal cells?

Science.gov (United States)

Moll, Guido; Hult, Annika; von Bahr, Lena; Alm, Jessica J; Heldring, Nina; Hamad, Osama A; Stenbeck-Funke, Lillemor; Larsson, Stella; Teramura, Yuji; Roelofs, Helene; Nilsson, Bo; Fibbe, Willem E; Olsson, Martin L; Le Blanc, Katarina

2014-01-01

Investigation into predictors for treatment outcome is essential to improve the clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We therefore studied the possible harmful impact of immunogenic ABO blood groups antigens - genetically governed antigenic determinants - at all given steps of MSC-therapy, from cell isolation and preparation for clinical use, to final recipient outcome. We found that clinical MSCs do not inherently express or upregulate ABO blood group antigens after inflammatory challenge or in vitro differentiation. Although antigen adsorption from standard culture supplements was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB plasma (ABP), dependent on antigen concentration and adsorption time. Compared to cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP elicited stronger blood responses after exposure to blood from healthy O donors in vitro, containing high titers of ABO antibodies. Clinical evaluation of hematopoietic stem cell transplant (HSCT) recipients found only very low titers of anti-A/B agglutination in these strongly immunocompromised patients at the time of MSC treatment. Patient analysis revealed a trend for lower clinical response in blood group O recipients treated with ABP-exposed MSC products, but not with HSA-exposed products. We conclude, that clinical grade MSCs are ABO-neutral, but the ABP used for washing and infusion of MSCs can contaminate the cells with immunogenic ABO substance and should therefore be substituted by non-immunogenic HSA, particularly when cells are given to immunocompentent individuals.

A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

NARCIS (Netherlands)

Hoefnagel, C. A.; Rutgers, M.; Buitenhuis, C. K.; Smets, L. A.; de Kraker, J.; Meli, M.; Carrel, F.; Amstutz, H.; Schubiger, P. A.; Novak-Hofer, I.

2001-01-01

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in

The therapeutic relationship after psychiatric admission.

LENUS (Irish Health Repository)

Roche, Eric

2014-03-01

The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

Efficacy of prophylactic splenectomy for proximal advanced gastric cancer invading greater curvature.

Science.gov (United States)

Ohkura, Yu; Haruta, Shusuke; Shindoh, Junichi; Tanaka, Tsuyoshi; Ueno, Masaki; Udagawa, Harushi

2017-05-25

For proximal gastric cancer invading the greater curvature, concomitant splenectomy is frequently performed to secure the clearance of lymph node metastases. However, prognostic impact of prophylactic splenectomy remains unclear. The aim of this study was to clarify the oncological significance of prophylactic splenectomy for advanced proximal gastric cancer invading the greater curvature. Retrospective review of 108 patients who underwent total or subtotal gastrectomy for advanced proximal gastric cancer involving the greater curvature was performed. Short-term and long-term outcomes were compared between the patients who underwent splenectomy (n = 63) and those who did not (n = 45). Patients who underwent splenectomy showed higher amount of blood loss (538 vs. 450 mL, p = 0.016) and morbidity rate (30.2 vs. 13.3, p = 0.041) compared with those who did not undergo splenectomy. In particular, pancreas-related complications were frequently observed among patients who received splenectomy (17.4 vs. 0%, p = 0.003). However, no significant improvement of long-term outcomes were confirmed in the cases with splenectomy (5-year recurrence-free rate, 60.2 vs. 67.3%; p = 0.609 and 5-year overall survival rates, 63.7 vs. 73.6%; p = 0.769). On the other hand, splenectomy was correlated with marginally better survival in patients with Borrmann type 1 or 2 gastric cancer (p = 0.072). For advanced proximal gastric cancer involving the greater curvature, prophylactic splenectomy may have no significant prognostic impact despite the increased morbidity rate after surgery. Such surgical procedure should be avoided as long as lymph node involvement is not evident.

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

Science.gov (United States)

Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Therapeutic alliance in a randomized clinical trial for bulimia nervosa.

Science.gov (United States)

Accurso, Erin C; Fitzsimmons-Craft, Ellen E; Ciao, Anna; Cao, Li; Crosby, Ross D; Smith, Tracey L; Klein, Marjorie H; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A; Peterson, Carol B

2015-06-01

This study examined the temporal relation between therapeutic alliance and outcome in two treatments for bulimia nervosa (BN). Eighty adults with BN symptoms were randomized to 21 sessions of integrative cognitive-affective therapy (ICAT) or enhanced cognitive-behavioral therapy (CBT-E). Bulimic symptoms (i.e., frequency of binge eating and purging) were assessed at each session and posttreatment. Therapeutic alliance (Working Alliance Inventory) was assessed at Sessions 2, 8, 14, and posttreatment. Repeated-measures analyses using linear mixed models with random intercepts were conducted to determine differences in alliance growth by treatment and patient characteristics. Mixed-effects models examined the relation between alliance and symptom improvement. Overall, patients in both treatments reported strong therapeutic alliances. Regardless of treatment, greater therapeutic alliance between (but not within) subjects predicted greater reductions in bulimic behavior; reductions in bulimic behavior also predicted improved alliance. Patients with higher depression, anxiety, or emotion dysregulation had a stronger therapeutic alliance in CBT-E than ICAT, while those with more intimacy problems had greater improvement in therapeutic alliance in ICAT compared to CBT-E. Therapeutic alliance has a unique impact on outcome, independent of the impact of symptom improvement on alliance. Within- and between-subjects effects revealed that changes in alliance over time did not predict symptom improvement, but rather that individuals who had a stronger alliance overall had better bulimic symptom outcomes. These findings indicate that therapeutic alliance is an important predictor of outcome in the treatment of BN. (c) 2015 APA, all rights reserved).

Experimental Myocardial Infarction: The quest for novel therapeutics

NARCIS (Netherlands)

Hout, G.P.J. van

2015-01-01

Myocardial infarction (MI) and its consequences are associated with high mortality rates and considerable health care costs. Novel therapeutics that protect the heart after MI are therefore required. To assess safety and efficacy before exposing patients to experimental compounds, thorough

Psychiatric therapeutic applications of virtual reality technology (VRT): research prospectus and phenomenological critique.

Science.gov (United States)

Bloom, R W

1997-01-01

There is theoretical and empirical research supporting the hypothesis that virtual reality technology (VRT) can be efficaciously applied to attenuate the symptoms of mental disorders (Baer, 1996; Rothbaum et al, 1995a, 1995b; Rothbaum et al, 1996.) Yet there is also research suggesting psychiatric therapeutic applications of VRT may induce noxious or unexpected psychological consequences (Kolasinski, 1996; Muscott & Gifford, 1994; Regan & Price, 1994; Regan & Ramsey, 1996; Strickland, 1995.) A prudent conclusion would be to advocate ever more sophisticated studies on psychiatric therapeutic applications of VRT concerning (1) increasing the overall socioadaptiveness of patients, (2) the robustness of moderating, modifying, or other intermediary variables effecting or affecting VRT therapeutic efficacy, and (3) variables, processes, and hypotheses generated from VRT applications in non-psychiatric fields.

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

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K. M. Maheswari

2014-01-01

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

Evaluation of the safety and efficacy of therapeutic bandage contact lenses on post-cataract surgery patients

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Dan-Na Shi

2018-02-01

Full Text Available AIM: To evaluate the safety of therapeutic bandage contact lens for post-cataract surgery patients and to illustrate its efficacy on post-operative comfort and tear-film stability. METHODS: A total of 40 participants were recruited and randomly divided into two groups. Group one was instructed to wear bandage contact lenses for a week and use antibiotic eye drops for a month since the first day after surgery. Group two received sub-conjunctival injection of tobramycin and was asked to wear eye pads on the first day after surgery and then were instructed to use antibiotic eye drops as the first group did. Ocular surface disease index (OSDI questionnaire, slit-lamp microscope examination of tear break-up time (TBUT, corneal fluorescein score (CFS, tear meniscus height (TMH together with anterior segment optical coherence tomography (AS-OCT and corneal topography were evaluated preoperatively and postoperatively. RESULTS: The subjective feeling (P=0.004, TBUT (P<0.001 and TMH (P=0.02 post-surgery had improved in patients who used bandage contact lenses compared with those who did not at 1wk post-surgery. Until three month postoperatively, the comfort degree (P=0.004 and TMH (P=0.01 of group two were still worse than group one. Moreover, TBUT (P<0.001 and CFS (P=0.004 of the group with eye pads got worse than the results before, whereas the group with bandage contact lenses recovered to normal. None of these patients had infections or other complications. CONCLUSION: Wearing therapeutic bandage contact lens after cataract surgery, compared with traditional eye-pads, is a safe method to improve tear-film stability and reduce post-operative discomfort without hindering corneal incision recovery.

Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334 ameliorates murine colitis

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Gupta R

2014-01-01

Full Text Available Ram Gupta,1 Anita R Chaudhary,2 Binita N Shah,1 Avinash V Jadhav,3 Shitalkumar P Zambad,1 Ramesh Chandra Gupta,4 Shailesh Deshpande,4 Vijay Chauthaiwale,4 Chaitanya Dutt4 1Department of Pharmacology, 2Cellular and Molecular Biology, 3Preclinical Safety Evaluation, 4Discovery, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gandhinagar, Gujarat, India Background and aim: Mucosal healing in inflammatory bowel disease (IBD can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods: The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results: TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion: Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor

Therapeutic Inertia in the New Landscape of Multiple Sclerosis Care

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Gustavo Saposnik

2018-03-01

Full Text Available The landscape of multiple sclerosis (MS treatment is constantly changing. Significant heterogeneity exists in the efficacy and risks associated with these therapies. Therefore, clinicians have the challenge to tailor treatment based on several factors (disease activity level, risk of progression, individual patient preferences and characteristics, personal expertise, etc., to identify the optimal balance between safety and efficacy. However, most clinicians have limited education in decision-making and formal training in risk management. Together, these factors may lead to therapeutic inertia (TI; defined as the absence of treatment initiation or intensification when therapeutic goals are unmet. TI may lead to suboptimal treatments choices, worse clinical outcomes, and more disability. This article provides a succinct overview on factors influencing TI in MS care.

The Cannabis Dilemma: A Review of Its Associated Risks and Clinical Efficacy.

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Zhang, Melvyn Weibin; Ho, Roger C M

2015-01-01

Cannabis, also known as marijuana, has 9-tetrahydrocannabinol as the main constituent. There has been strict legislation governing the utilization of cannabis locally and worldwide. However, there has been an increasing push to make cannabis legalized, in view of its potential medical and therapeutic effects, for various medical disorders ranging from development disorders to cancer treatment, and being an adjunctive medication for various neurological conditions. It is the aim of this review paper to explore the evidence base for its proposed therapeutic efficacy and to compare the evidence base supporting its proposed therapeutic efficacy with its known and well-researched medical and psychiatric side effects.

The Cannabis Dilemma: A Review of Its Associated Risks and Clinical Efficacy

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Melvyn Weibin Zhang

2015-01-01

Full Text Available Cannabis, also known as marijuana, has 9-tetrahydrocannabinol as the main constituent. There has been strict legislation governing the utilization of cannabis locally and worldwide. However, there has been an increasing push to make cannabis legalized, in view of its potential medical and therapeutic effects, for various medical disorders ranging from development disorders to cancer treatment, and being an adjunctive medication for various neurological conditions. It is the aim of this review paper to explore the evidence base for its proposed therapeutic efficacy and to compare the evidence base supporting its proposed therapeutic efficacy with its known and well-researched medical and psychiatric side effects.

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

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Bonglim Joo

2017-05-01

Full Text Available The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children (n = 8 and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological comorbidity; children with intellectual impairment were excluded (IQ < 80. The program was carried out weekly for four sessions. In each of the 4 weeks, children's session content addressed self, emotion, coping skills, and finishing up, respectively; and parents' session content targeted family dynamic and emotional intervention, coping skills, childcare and education, and finishing up, respectively. Clinical psychologists administered psychological assessments (viz., Child Behavior Checklist, Pediatric Quality of Life Inventory, Parenting Stress Index, Beck Depression Inventory, Children's Depression Inventory, and Revised Children's Manifest Anxiety Scale at pre- and post-intervention, and administered satisfaction surveys following the intervention. Participants' opinions about the program's necessity, contents, and process, and participants' overall program satisfaction were analyzed. Parents and children reported high levels of satisfaction with the program. Externalizing behavioral problems, anxiety/depression, and emotional functioning from quality of life showed improvement after the intervention. Although not statistically significant, total child stress trended downward from pre- to post-intervention. A four-session structured therapeutic psycho-educational program for children and adolescents with chronic neurological illness and their parents was successfully implemented, showing good compliance and high satisfaction and efficacy.

Development of Class IIa Bacteriocins as Therapeutic Agents

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Christopher T. Lohans

2012-01-01

Full Text Available Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as the optimization of their production and purification. The suitability of bacteriocins as pharmaceuticals is explored through determinations of cytotoxicity, effects on the natural microbiota, and in vivo efficacy in mouse models. Recent results suggest that class IIa bacteriocins show promise as a class of therapeutic agents.

Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.

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Masuko, Kazutaka; Wakita, Daiko; Togashi, Yuji; Kita, Toshiyuki; Kitamura, Hidemitsu; Nishimura, Takashi

2015-01-01

To elucidate the immunologic mechanisms of artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which indicated a great vaccine efficacy in human cancers, we prepared ovalbumin (OVA)-H/K-HELP by conjugating killer and helper epitopes of OVA-model tumor antigen via a glycine-linker. Vaccination of C57BL/6 mice with OVA-H/K-HELP (30 amino acids) but not with short peptides mixture of class I-binding peptide (8 amino-acids) and class II-binding peptide (17 amino-acids) combined with adjuvant CpG-ODN (cytosine-phosphorothioate-guanine oligodeoxynucleotides), induced higher numbers of OVA-tetramer-positive CTL with concomitant activation of IFN-γ-producing CD4(+) Th1 cells. However, replacement of glycine-linker of OVA-H/K-HELP with other peptide-linker caused a significant decrease of vaccine efficacy of OVA-H/K-HELP. In combination with adjuvant CpG-ODN, OVA-H/KHELP exhibited greater vaccine efficacy compared with short peptides vaccine, in both preventive and therapeutic vaccine models against OVA-expressing EG-7 tumor. The elevated vaccine efficacy of OVAH/K-HELP might be derived from the following mechanisms: (i) selective presentation by only professional dendritic cells (DC) in vaccinated draining lymph node (dLN); (ii) a long-term sustained antigen presentation exerted by DC to stimulate both CTL and Th1 cells; (iii) formation of three cells interaction among DC, Th and CTL. In comparative study, H/K-HELP indicated stronger therapeutic vaccine efficacy compared with that of extended class I synthetic long peptide, indicating that both the length of peptide and the presence of Th epitope peptide were crucial aspects for preparing artificially synthesized H/K-HELP vaccine. Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

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Cataland, S R; Wu, H M

2015-06-01

Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

Tofacitinib Suppresses Antibody Responses to Protein Therapeutics in Murine Hosts1

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Onda, Masanori; Ghoreschi, Kamran; Steward-Tharp, Scott; Thomas, Craig; O’Shea, John J.; Pastan, Ira H.; FitzGerald, David J.

2014-01-01

Immunogenicity remains the ‘Achilles’ heel’ of protein-based therapeutics. Anti-drug antibodies produced in response to protein therapeutics can severely limit both the safety and efficacy of this expanding class of agent. Here we report that monotherapy of mice with tofacitinib (the Janus kinase inhibitor) quells antibody responses to an immunotoxin derived from the bacterial protein, Pseudomonas exotoxin A, as well as to the model antigen, keyhole limpet hemocyanin. Thousandfold reductions in IgG1 titers to both antigens were observed 21 days post-immunization. In fact, suppression was evident for all IgG isotypes and IgM. A reduction in IgG3 production was also noted with a thymus-independent type II antigen. Mechanistic investigations revealed that tofacitinib treatment led to reduced numbers of CD127+ pro-B cells. Furthermore, we observed fewer germinal center B cells and the impaired formation of germinal centers of mice treated with tofacitinib. Since normal immunoglobulin levels were still present during the tofacitinib treatment, this agent specifically reduced anti-drug antibodies, thus preserving the potential efficacy of biological therapeutics, including those that are used as cancer therapeutics. PMID:24890727

Gender Differences in Career Self-Efficacy: Combining a Career with Home and Family.

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Stickel, Sue A.; Bonett, Rhonda M.

1991-01-01

Piloted Career Attitude Scale, measure of career self-efficacy, with college students (n=130) and examined gender differences in career self-efficacy. Compared to men, women reported greater efficacy in terms of combining traditional career with family and home activities. Women also revealed greater confidence that they could competently handle…

Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor.

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Honma, Daisuke; Kanno, Osamu; Watanabe, Jun; Kinoshita, Junzo; Hirasawa, Makoto; Nosaka, Emi; Shiroishi, Machiko; Takizawa, Takeshi; Yasumatsu, Isao; Horiuchi, Takao; Nakao, Akira; Suzuki, Keisuke; Yamasaki, Tomonori; Nakajima, Katsuyoshi; Hayakawa, Miho; Yamazaki, Takanori; Yadav, Ajay Singh; Adachi, Nobuaki

2017-10-01

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B-cell lymphoma cells harboring gain-of-function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The state-of-play and future of antibody therapeutics.

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Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

2017-12-01

It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

[Therapeutic efficacy of compound Xuanju capsule on autoimmune prostatitis in rats: an experimental study].

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Li, Tian-Fu; Wu, Qiu-Yue; Li, Wei-Wei; Zhang, Cui; Li, Na; Shang, Xue-Jun; Xia, Xin-Yi; Xu, Hao-Qin; Huang, Yu-Feng

2014-05-01

To evaluate the therapeutic effect of Compound Xuanju Capsule (CXC) on autoimmune prostatitis in rat models. Sixty healthy male Wistar rats were randomly divided into five groups of equal number: blank control, low-concentration purified prostate protein (low-conc PPP), low-conc PPP + CXC treatment, high-concentration PPP (hi-con PPP), and hi-conc PPP + CXC treatment. Autoimmune prostatitis models were established by intragastric administration of PPP solution at 15 mg/ml (low concentration) and 80 mg/ml, respectively. At 30 days after modeling, the rats in the blank control and low-conc and hi-conc PPP model groups were treated with normal saline, and those in the other two groups with CXC at a daily dose of 0.068 g/ml. At 30, 45, and 60 days, all the animals were sacrificed for observation of pathological changes in the prostate tissue and determination of the levels of IL-8, IL-10, and TNF-alpha in the serum. Compared with the PPP models, the hi-conc PPP + CXC group showed significantly reduced levels of IL-8 and TNF-alpha in the serum at 45 days ([148.54 +/- 17.23] and [62.14 +/- 5.59] pg/ml vs [100.77 +/- 11.08] and [32.63 +/- 2.91] pg/ml, P microscope. Compound Xuanju Capsule is efficacious on autoimmune prostatis in rats by reducing inflammatory changes in the prostate tissue and improving the expression of inflammatory factors.

Efficacy of Morin as a Potential Therapeutic Phytocomponent: Insights into the Mechanism of Action

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Amarendranath Choudhury

2017-11-01

Full Text Available Morin (3,5,7,29,49-pentahydroxyflavone is a yellow colour natural bioflavonoid abundantly available in different species of Moraceae family. Besides this, Morin is also harvested from several other sources like tea, coffee, cereals, fruits and red wine. Anti-oxidant, anti-inflammatory, and antiproliferative potency of Morin is well established in both in vivo and in vitro experiments. Among all major sources of Morin, Almond (Prunus dulcis, Fig (Chlorophora tinctoria, and Indian guava (Psidium guajava contains high quantity of it. Easy availability, less side effects and robust functional properties have encouraged the use of these plants in the traditional herbal medicine. In last few decades, the studies on Morin have opened up a whole new era in the therapeutic medicine. Besides anti-oxidant, anti-inflammatory, and antiproliferative activity, Morin has also been reported as a potential neuroprotective agent against many neurological diseases including Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. According to published reports, the underlying neuroprotective mechanism of Morin is focused mainly on its capacity to inhibit oxidative stress in brain. However, recent data also supports its efficacy in neuroprotection by effectively interacting in the β‒amyloid pathways, inflammatory pathways, and apoptotic pathways. In the present review, we have accumulated all the protective contributions of Morin and intended to drag a mechanistic pathway containing the molecular events leading to the protection against various anomalies.

Efficacy of ivermectin, closantel and fenbendazole against gastrointestinal nematodes of sheep in Kashmir valley.

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Tramboo, S R; Shahardar, R A; Allaie, I M; Wani, Z A; Abbas, Maria

2017-06-01

The present work was undertaken to evaluate the therapeutic efficacy of ivermectin, closantel and fenbendazole under field conditions against Gastrointestinal Nematodes (GIN) of cross bred merino sheep in Budgam area of Kashmir Valley. A total of 115 sheep having Egg per gram of faeces (EPG) greater than or equal to 150 (mean EPG 258.89) were selected. The animals were randomly divided into four groups comprising of 30 animals each in three treatment groups (ivermectin, closantel and fenbendazole) and twenty-five in fourth untreated infected control group. Faecal samples from the selected animals were collected on day '0' pre treatment and on days 8th and 14th post treatment. Based on Faecal Egg Count Reduction Test (FECRT), ivermectin was found to be 98.80 % effective against strongyles on 8th day post treatment, however an efficacy of 100 % was seen against strongyle worms on 14th day post treatment. 98.80 and 100 % efficacy was observed on day 8th post treatment against strongyles in case of closantel and fenbendazole respectively, however efficacy decreased to 97.60 and 98.8 % respectively on 14th day post treatment. There was no evidence of development of resistance by GIN of cross bred merino sheep in District Budgam of Kashmir Valley to ivermectin, closantel and fenbendazole.

Therapeutic Vaccine Against Primate Papillomavirus Infections of the Cervix

DEFF Research Database (Denmark)

Ragonnaud, Emeline; Andersson, Anne-Marie C; Mariya, Silmi

2017-01-01

Currently available prophylactic vaccines have no therapeutic efficacy for preexisting human papillomavirus (HPVs) infections, do not target all oncogenic HPVs and are insufficient to eliminate the burden of HPV induced cancer. We aim to develop an alternative HPV vaccine which is broadly effective...

Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice.

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Badamchi-Zadeh, Alexander; Tartaglia, Lawrence J; Abbink, Peter; Bricault, Christine A; Liu, Po-Ting; Boyd, Michael; Kirilova, Marinela; Mercado, Noe B; Nanayakkara, Ovini S; Vrbanac, Vladimir D; Tager, Andrew M; Larocca, Rafael A; Seaman, Michael S; Barouch, Dan H

2018-04-01

Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Copyright © 2018 Badamchi-Zadeh et al.

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

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Kannan, Rangaramanujam

2007-03-01

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

Therapeutic efficacy of bipolar radiofrequency thermotherapy for patients with chronic prostatitis: a retrospective analysis of 26 cases.

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Lim, Ju Young; Shim, Seung Bum; Yoo, Dong Hoon; Park, Young Woong; Kim, Jong Yeon; Noh, Joon Hwa

2012-07-01

Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 years old and diagnosed with CP (National Institutes of Health [NIH]-category III) was performed. Twenty patients were diagnosed with inflammatory CP (NIH-category IIIa) and the rest with noninflammatory CP (NIH-category IIIb). We used the Tempro system at an intraprostatic temperature of 55℃ for 50 minutes with a medium heating rate. All patients also completed the NIH-Chronic Prostatitis Symptom Index (CPSI) before and after treatment. In the patients diagnosed with CP, the mean serum prostate-specific antigen (PSA) level was 0.9±0.3 ng/ml, the prostate volume was 27.1±5.5 g, and the average score for all 3 domains on the NIH-CPSI significantly decreased. The total scores decreased from 19.8±7.1 to 11.1±7.0, the pain domain decreased from 8.6±3.1 to 4.8±3.1, the voiding symptom domain decreased from 5.1±1.8 to 2.9±1.8, and the effect on the quality of life decreased from 6.1±2.2 to 3.4±2.2 (pthermotherapy for patients with CP intractable to conventional medication can provide significant improvement in the NIH-CPSI. Large, randomized controlled trials will also be required to confirm the efficacy of this therapy.

Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

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Tripathy, Sushant

Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

Efficacy of oral moxifloxacin for aerobic vaginitis.

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Wang, C; Han, C; Geng, N; Fan, A; Wang, Y; Yue, Y; Zhang, H; Xue, F

2016-01-01

The purpose of this study was to investigate the therapeutic efficacy of oral moxifloxacin for aerobic vaginitis (AV). We also identified factors that are associated with therapeutic efficacy. This prospective study enrolled general gynecological outpatients at Tianjin Medical University General Hospital between September 2012 and May 2014. Women diagnosed with AV (n = 102) were recruited. All enrolled women were treated with oral moxifloxacin, 400 mg once daily for 6 days (one course). Therapeutic efficacy was evaluated based on microscopic criteria, and cure rates were calculated. Women who were microscopically improved (but not cured) received a second course of therapy. Women classified with microscopic failure were treated using other strategies. Univariate and multivariate logistic regression analysis was used to identify factors that may be associated with a cure after one course of therapy. After one course of therapy, 65.7 % (67/102) of women were cured, 29.4 % (30/102) of women were improved (but not cured), 4.9 % (5/102) of women failed to respond to the therapy. After two courses of therapy, 85.3 % (87/102) of women were cured, 9.8 % (10/102) of women were improved, 4.9 % (5/102) of women failed to respond to the therapy, and clinical improvement was achieved in additional women. In the multivariate logistic regression analysis, women with a baseline vaginal pH value of vaginal pH value of ≥5.0 (OR, 3.503; 95 % CI, 1.278-9.601). Moxifloxacin is an effective therapeutic option for patients with AV. Most women with AV were cured with one course of moxifloxacin. For those with a higher vaginal pH value of ≥5.0 before treatment, two courses of therapy should be considered.

Personal identity narratives of therapeutic songwriting participants following Spinal Cord Injury: A case series analysis.

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Roddy, Chantal; Rickard, Nikki; Tamplin, Jeanette; Baker, Felicity Anne

2018-07-01

Spinal Cord Injury (SCI) patients face unique identity challenges associated with physical limitations, higher comorbid depression, increased suicidality and reduced subjective well-being. Post-injury identity is often unaddressed in subacute rehabilitation environments where critical physical and functional rehabilitation goals are prioritized. Therapeutic songwriting has demonstrated prior efficacy in promoting healthy adjustment and as a means of expression for post-injury narratives. The current study sought to examine the identity narratives of therapeutic songwriting participants. Case-series analysis of the individual identity trajectories of eight individuals. Subacute rehabilitation facility, Victoria, Australia. Eight individuals with an SCI; 7 males and 1 female. Six-week therapeutic songwriting intervention facilitated by a music therapist to promote identity rehabilitation. Identity, subjective well-being and distress, emotional state. Three participants demonstrated positive trajectories and a further three showed negative trajectories; remaining participants were ambiguous in their response. Injury severity differentiated those with positive trajectories from those with negative trajectories, with greater injury severity apparent for those showing negative trends. Self-concept also improved more in those with positive trajectories. Core demographic variables did not however meaningfully predict the direction of change in core identity or wellbeing indices. Identity-focused songwriting holds promise as a means of promoting healthy identity reintegration. Further research on benefits for those with less severe spinal injuries is warranted.

Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial.

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Johnston, Celeste; Campbell-Yeo, Marsha; Rich, Bonnie; Whitley, Julie; Filion, Francoise; Cogan, Jennifer; Walker, Claire-Dominique

2013-09-01

Preterm neonates below 30 weeks' gestational age undergo numerous painful procedures. Many management approaches are not appropriate for this population. Therapeutic Touch, an alternative approach based on the theory of energy medicine, has been shown to promote physiological stability in preterm neonates and reduce pain in some adult studies. The objective was to determine whether Therapeutic Touch is efficacious in decreasing pain in preterm neonates. Infants Touch (n = 27) with infant behind curtains, leaving the curtained area for the heel lance, performed by another. In the sham condition (n = 28), the therapist stood by the incubator with hands by her side. The Premature Infant Pain Profile was used for pain response and time for heart rate to return to baseline for recovery. Heart rate variability and stress response were secondary outcomes. There were no group differences in any of the outcomes. Mean Premature Infant Pain Profile scores across 2 minutes of heel lance procedure in 30-second blocks ranged from 7.92 to 8.98 in the Therapeutic Touch group and 7.64 to 8.46 in the sham group. Therapeutic Touch given immediately before and after heel lance has no comforting effect in preterm neonates. Other effective strategies involving actual touch should be considered.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

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Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

2017-01-01

Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

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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

[Relationship experiences and therapeutic outcome in inpatient psychotherapy].

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Sammet, Isa; Staats, Herrmann; Schauenburg, Henning

2004-01-01

Inpatient psychotherapy includes the patient's manifold contacts with different therapists, nurses and fellow patients. The present study investigated the association between these multiple relationships and therapy outcome. Pre-post measures of symptom load (Brief Symptom Inventory), interpersonal problems (IIP) and self-efficacy (SEB) were used to define three groups with positive (N=129), unchanged (N=44) or negative (N=40) outcome. These groups were compared 1) by their alliance with an individual therapist, their relationship to the therapeutic team, their experience of cohesion and climate concerning fellow patients in the ward (measured weekly by the "Stationserfahrungsbogen" SEB), and 2) by their differences in mean correlations between the courses of relationship experiences and symptom load. Cohesion and relationship to the therapeutic team were not associated with therapy outcome. Therapeutic alliance with the individual therapist and climate among fellow patients turned out to be moderate indicators of the therapeutic outcome. It is recommended to include these process parameters systematically into the process diagnostics of inpatient psychotherapy.

The Efficacy of Cardiac Anti-miR-208a Therapy Is Stress Dependent

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Eding, Joep E C; Demkes, Charlotte J; Lynch, Joshua M; Seto, Anita G; Montgomery, Rusty L; Semus, Hillary M; Jackson, Aimee L; Isabelle, Marc; Chimenti, Stefano; van Rooij, Eva

2017-01-01

MicroRNAs (miRNAs) are important regulators of biology and disease. Recent animal efficacy studies validate the therapeutic benefit of miRNA modulation and underscore the therapeutic value of miRNA-targeting oligonucleotides. However, whether disease conditions (stress) influence the pharmacological

Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine : efficacy, safety and dosing

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van den Broek, Marcel P. H.; Rademaker, Carin M. A.; van Straaten, Henrica L. M.; Huitema, Alwin D. R.; Toet, Mona C.; de Vries, Linda S.; Egberts, Antoine C. G.; Groenendaal, Floris

BACKGROUND: Lidocaine is an antiarrythmicum used as an anticonvulsant for neonatal seizures, also during therapeutic hypothermia following (perinatal) asphyxia. Hypothermia may affect the efficacy, safety and dosing of lidocaine in these patients. OBJECTIVE: To study the efficacy and safety of

Therapeutic efficacy of milbemycin oxime/praziquantel oral formulation (Milbemax® against Thelazia callipaeda in naturally infested dogs and cats

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Motta Bruna

2012-05-01

Full Text Available Abstract Background Over the last few decades, canine and feline thelaziosis caused by Thelazia callipaeda eye worms has gained the attention of the veterinary community due to the spread of this ocular infestation in geographical areas previously regarded as non endemic. The therapeutic efficacy of milbemycin oxime/praziquantel tablets (Milbemax® against T. callipaeda was tested in naturally infested dogs and cats. Methods From January 2009 to July 2011 a placebo controlled and randomized field study was conducted in T. callipaeda endemic areas of Switzerland (CH and Italy (ITA involving client-owned animals. Dogs (n = 56 and cats (n = 31 were physically examined at enrolment Day 0 (D0 and twice afterwards (D7 and D14. Infested animals were orally treated with Milbemax® or with placebo tablets on D0 and, if an animal was found still infested with T. callipaeda, also on D7. On D14 nematodes were flushed from the conjunctiva, identified and counted. Results Out of 56 dogs, 43 were included in the statistical analysis, whereas 13 were excluded because the products under investigation were not administered with food, as required by the label. On D7 and D14, 72.7% and 90.9% of treated dogs were eye worm free, whereas in the placebo group 95.2% and 76.2% still harbored nematodes, resulting in a mean percentage worm count reduction for the Milbemax® group of 86.1% and 96.8%, respectively. Both results were significantly higher (p = 0.0001 than the placebo group. Out of the 31 cats included in the study at D7 and D14, 53.3% and 73.3% treated with Milbemax® were free of T. callipaeda, while 81.3% and 73.3 in the placebo group were still harbouring eye worms, resulting in a mean percentage worm count reduction for the treated group of 62.2% and 80.0%, respectively. Both results were significantly higher (p = 0.0106 and p = 0.0043 than the placebo group. Conclusions The commercial formulation of milbemycin oxime at the minimal dose

Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.

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Jing Lin

Full Text Available POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4 vs. (25.1 ± 19.1 pg/ml, P 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

Comparison of efficacy and safety of topiramate with gabapentin in migraine prophylaxis: randomized open label control trial

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Zain, S.; Khan, M.; Alam, R.; Zafar, I.; Ahmed, S.

2013-01-01

Objective: To compare the efficacy and safety of topiramate with gabapentin in the prophylaxis of migraine patients. Methods: A 12-week randomised open label control trial was conducted at the Department of Pharmacology and Therapeutics, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January to March 2011 involving 80 outpatients who had a history of migraine. The sample was divided into two equal groups. Primary efficacy measure was changed into mean monthly migraine frequency. Secondary efficacy measure included reduction in severity and average duration of an attack. Chi square test and paired t-test were used to analyse the data through SPSS 15. Result: Reduction in mean monthly migraine frequency (10.67+-4.25 to 1.82+-2.02) in the topiramate group was significantly greater compared with (11.97+-4.452 to 2.73+-2.59) that in the gabapentin group (p<0.001). Reduction in severity from 6.60+-2.122 to 1.03+-0.92 in the topiramate group was also significantly greater compared with 6.93+-1.90 to 1.18+-1.01 in the gabapentin group (p<0.001). Reduction in the average duration of attacks from 25.77+-22.32 hours to 1.0 1.06 hours in the topiramate group was significantly greater compared with 22.20+-20.72 to 1.08+-1.40 hours in the gabapentin group (p<0.001). Weight loss and numbness were common adverse effects in the topiramate group. Dizziness, weight gain and somnolence were reported in the gabapentin group. Conclusion: Gabapentin appeared well tolerated in 30(75%) patients compared to topiramate in 23(57.5%) patients. Both drugs were equally effective in migraine prophylaxis. (author)

Influence of drug colour on perceived drug effects and efficacy.

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Tao, Da; Wang, Tieyan; Wang, Tieshan; Qu, Xingda

2018-02-01

A drug's physical characteristics, such as colour, could be factors influencing its therapeutic effects. It is not well understood whether people's expectations on drug effects and efficacy are affected by colour, especially among Chinese population. This study was conducted to examine people's expectations on drug effects and efficacy on the basis of drug colour, and to reveal possible gender differences in colour-related drug expectations. Participants (n = 224) were asked to classify seven single-coloured and six two-coloured capsules into one of four categories of drug effects, and to indicate the strength of drug efficacy. It is found that all the coloured capsules yielded non-chance distributions in classifications of drug effects, with six single-coloured and four two-coloured capsules associated with specific drug effects. Colour also conveyed differential strengths of drug efficacy in general and in relation to specific drug effects. There were gender differences in drug expectations for some colours and colour combinations. Practitioner Summary: Drug colour was found to have impacts on perceived drug effects and efficacy. The findings from the present study can be used by ergonomics practitioners to design appropriate drug colours in support of drug differentiation, therapeutic effects and medication adherence.

Therapeutic Silencing of Bcl-2 by Systemically Administered siRNA Nanotherapeutics Inhibits Tumor Growth by Autophagy and Apoptosis and Enhances the Efficacy of Chemotherapy in Orthotopic Xenograft Models of ER (− and ER (+ Breast Cancer

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Ibrahim Tekedereli

2013-01-01

Full Text Available Bcl-2 is overexpressed in about a half of human cancers and 50–70% of breast cancer patients, thereby conferring resistance to conventional therapies and making it an excellent therapeutic target. Small interfering RNA (siRNA offers novel and powerful tools for specific gene silencing and molecularly targeted therapy. Here, we show that therapeutic silencing of Bcl-2 by systemically administered nanoliposomal (NL-Bcl-2 siRNA (0.15 mg siRNA/kg, intravenous twice a week leads to significant antitumor activity and suppression of growth in both estrogen receptor-negative (ER(− MDA-MB-231 and ER-positive (+ MCF7 breast tumors in orthotopic xenograft models (P < 0.05. A single intravenous injection of NL-Bcl-2-siRNA provided robust and persistent silencing of the target gene expression in xenograft tumors. NL-Bcl-2-siRNA treatment significantly increased the efficacy of chemotherapy when combined with doxorubicin in both MDA-MB-231 and MCF-7 animal models (P < 0.05. NL-Bcl-2-siRNA treatment-induced apoptosis and autophagic cell death, and inhibited cyclin D1, HIF1α and Src/Fak signaling in tumors. In conclusion, our data provide the first evidence that in vivo therapeutic targeting Bcl-2 by systemically administered nanoliposomal-siRNA significantly inhibits growth of both ER(− and ER(+ breast tumors and enhances the efficacy of chemotherapy, suggesting that therapeutic silencing of Bcl-2 by siRNA is a viable approach in breast cancers.

Approaching Environmental Sustainability: Perceptions of Self-Efficacy and Changeability.

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Schutte, Nicola S; Bhullar, Navjot

2017-04-03

This paper describes a model focused on the role of self-efficacy and belief in changeability of behavior in motivating environmentally sustainable behavior. The model was tested in two studies. The first study found that participants who had greater self-efficacy for sustainability behavior and a greater belief in their changeability of sustainability behavior had a higher level of approach motivation toward sustainability behavior and reported more such actual behavior. The second study investigated the effect of brief interventions intended to increase perception of self-efficacy for sustainability-related purchasing and changeability of sustainability-related purchasing. The intervention that focused on enhancing self-efficacy for making sustainability-related purchases had the strongest impact on intention to purchase. These findings have implications for interventions intended to change behavior related to environmental sustainability.

Therapeutic efficacy of AS2077715 against experimental tinea pedis in guinea pigs in comparison with terbinafine.

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Ohsumi, Keisuke; Murai, Hidetsugu; Nakamura, Ikko; Watanabe, Masato; Fujie, Akihiko

2014-10-01

AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal strain Capnodium sp. 339855. This compound has potent inhibitory activity against Trichophyton mentagrophytes mitochondrial cytochrome bc1 complex (complex III) and potent fungicidal activity against T. mentagrophytes, as measured in vitro. Here, we compared the effects of AS2077715 and terbinafine in a guinea pig model of tinea pedis. In a treatment regimen started from the day 7 after infection, 10 daily oral doses of 10 and 20 mg kg(-1) AS2077715 and 20 mg kg(-1) of terbinafine significantly decreased fungal colony-forming units (CFUs) in foot pad skin. In a treatment regimen started from the day 11 after infection, 20 mg kg(-1) AS2077715 significantly reduced fungal CFUs in foot pad skin after 7 daily doses in comparison with 20 mg kg(-1) terbinafine-treated guinea pigs. Our findings suggest that in vivo potency and efficacy of AS2077715 are equal to or greater than that of terbinafine, positioning AS2077715 as a good candidate for use in treating trichophytosis.

Therapeutic efficacy of percutaneous radiofrequency ablation versus microwave ablation for hepatocellular carcinoma.

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Lei Zhang

Full Text Available The aim of this study was to investigate the therapeutic efficacy of percutaneous radiofrequency (RF ablation versus microwave (MW ablation for hepatocellular carcinoma (HCC measuring ≤ 5 cm in greatest diameter. From January 2006 to December 2006, 78 patients had undergone RF ablation whereas 77 had undergone MW ablation. Complete ablation (CA, local tumour progression (LTP and distant recurrence (DR were compared. The overall survival curves were calculated with the Kaplan-Meier technique and compared with the log-rank test. The CA rate was 83.4% (78/93 for RF ablation and 86.7%(91/105 for MW ablation. The LTP rate was 11.8% (11/93 for RF ablation and 10.5% (11/105 for MW ablation. DR was found in 51 (65.4% in the RF ablation and 62 (80.5% in the MW ablation. There was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.780 and the 1-, 3-, and 5-year disease-free survival rates (P = 0.123 between RF and MW ablation. At subgroup analyses, for patients with tumors ≤ 3.0 cm, there was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.067 and the corresponding disease-free survival rates(P = 0.849. For patients with tumor diameters of 3.1-5.0 cm, the 1-, 3-, and 5-year overall survival rates were 87.1%, 61.3%, and 40.1% for RF ablation and 85.4%, 36.6%, and 22% for MW ablation, with no significant difference (P = 0.068. The corresponding disease-free survival rates were 74.2%, 54.8%, and 45.2% for the RF ablation group and 53.3%, 26.8%, and 17.1% for the MW ablation group. The disease-free survival curve for the RF ablation group was significantly better than that for the MW ablation group (P = 0.018. RF ablation and MW ablation are both effective methods in treating hepatocellular carcinomas, with no significant differences in CA, LTP, DR, and overall survival.

Stimuli-responsive nanomaterials for therapeutic protein delivery.

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Lu, Yue; Sun, Wujin; Gu, Zhen

2014-11-28

Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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

2008-01-01

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

Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

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Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

2017-12-01

Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 + T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

Therapeutic Vaccination for HPV Induced Cervical Cancers

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Joeli A. Brinkman

2007-01-01

Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

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Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

Interactions of silica nanoparticles with therapeutics for oxidative stress attenuation in neurons

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White-Schenk, Desiree; Shi, Riyi; Leary, James F.

2015-03-01

Oxidative stress plays a major role in many disease pathologies, notably in the central nervous system (CNS). For instance, after initial spinal cord injury, the injury site tends to increase during a secondary chemical injury process based on oxidative stress from necrotic cells and the inflammatory response. Prevention of this secondary chemical injury would represent a major advance in the treatment of people with spinal cord injuries. Few therapeutics are useful in combating such stress in the CNS due to side effects, low efficacy, or half-life. Mesoporous silica nanoparticles show promise for delivering therapeutics based on the formation of a porous network during synthesis. Ideally, they increase the circulation time of loaded therapeutics to increase the half-life while reducing overall concentrations to avoid side effects. The current study explored the use of silica nanoparticles for therapeutic delivery of anti-oxidants, in particular, the neutralization of acrolein which can lead to extensive tissue damage due to its ability to generate more and more copies of itself when it interacts with normal tissue. Both an FDA-approved therapeutic, hydralazine, and natural product, epigallocatechin gallate, were explored as antioxidants for acrolein with nanoparticles for increased efficacy and stability in neuronal cell cultures. Not only were the nanoparticles explored in neuronal cells, but also in a co-cultured in vitro model with microglial cells to study potential immune responses to near-infrared (NIRF)-labeled nanoparticles and uptake. Studies included nanoparticle toxicity, uptake, and therapeutic response using fluorescence-based techniques with both dormant and activated immune microglia co-cultured with neuronal cells.

Therapeutic approaches for celiac disease

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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

Cooperative nanomaterials systems for cancer diagnosis and therapeutics

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Park, Ji Ho

developed. Gold nanorods localized through vascular circulation to the tumor region, where they reported their location and converted near infrared (NIR) radiation to thermal energy. The local photothermal heating enabled to enhance tumor-specific drug release from thermally labile therapeutic liposomes or induce more binding sites for targeted therapeutic liposomes. The combination of local hyperthermia and chemotherapy in the cooperative nanosystems significantly enhanced therapeutic efficacy relative to individual therapies.

Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

International Nuclear Information System (INIS)

Banerjee, Subhamoy; Ghosh, Siddhartha Sankar; Sahoo, Amaresh Kumar; Chattopadhyay, Arun

2014-01-01

The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV–vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells. (paper)

Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

Science.gov (United States)

Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

2014-08-01

The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

The anthelmintic efficacy of fenbendazole in the control of Moniezia expansa and Trichuris ovis in sheep.

Science.gov (United States)

Townsend, R B; Kelly, J D; James, R; Weston, I

1977-11-01

The anthelmintic efficacy of fenbendazole (methyl 5-(phenyl-thio)-2-benzimidazole-carbamate) against Moniezia expansa and Trichuris ovis was tested. At dose rates of 5 mg per kg and above, efficacies were found to be greater than 91 percent against M expansa and greater than 92 per cent against T ovis. At these dose rates efficacy on egg suppression was 100 per cent for Moniezia and greater than 97 per cent for Trichuris.

Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

DEFF Research Database (Denmark)

Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

formulation in contrast to that of clinically available tamoxifen citrate when measured as function of hepatotoxicity markers and histopathological changes. CONCLUSIONS: In nutshell, co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great potential in improving the therapeutic efficacy...

Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

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Degrazio, Dominick

Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level. Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to recombinantly derived therapeutic biologics. Concerns associated with this transformation are becoming prominent, as therapeutic biologics are uncharacteristic to small-molecule drugs. Maintaining the stability of a therapeutic biologic is a combination of balancing intrinsic factors and external elements within the biologic's microenvironment. An important aspect of this balance is relegated to the overall compatibility of primary, parenteral container-closure systems with therapeutic biologics

Prognostic evaluation of primary biliary cirrhosis and its value in guiding therapeutic regimens

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HUANG Chunyang

2016-07-01

Full Text Available Prognostic evaluation of patients with primary biliary cirrhosis (PBC and how to improve the prognosis have attracted much attention. Further therapeutic regimens for PBC patients with poor prognosis has become the direction of clinical and scientific studies. This article summarizes the association between baseline indices and prognosis and prognostic evaluation of patients undergoing ursodeoxycholic acid (UDCA treatment, introduces the current status of UDCA combined with budesonide, fibrates, and obeticholic acid for patients with poor response to UDCA and the drugs being developed, and analyzes the influencing factors for prognosis and efficacy of UDCA. It is pointed out that prognosis and efficacy should be evaluated before and during UDCA treatment, and that therapeutic regimens should be adjusted in time to improve prognosis.

Molecular Imaging of Gene Expression and Efficacy following Adenoviral-Mediated Brain Tumor Gene Therapy

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Alnawaz Rehemtulla

2002-01-01

Full Text Available Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD along with an optical reporter gene (luciferase. Following intratumoral injection of the vector into orthotopic 9L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging

Therapeutic outcomes, assessments, risk factors and mitigation efforts of immunogenicity of therapeutic protein products.

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Yin, Liusong; Chen, Xiaoying; Vicini, Paolo; Rup, Bonita; Hickling, Timothy P

2015-06-01

Therapeutic protein products (TPPs) are of considerable value in the treatment of a variety of diseases, including cancer, hemophilia, and autoimmune diseases. The success of TPP mainly results from prolonged half-life, increased target specificity and decreased intrinsic toxicity compared with small molecule drugs. However, unwanted immune responses against TPP, such as generation of anti-drug antibody, can impact both drug efficacy and patient safety, which has led to requirements for increased monitoring in regulatory studies and clinical practice, termination of drug development, or even withdrawal of marketed products. We present an overview of current knowledge on immunogenicity of TPP and its impact on efficacy and safety. We also discuss methods for measurement and prediction of immunogenicity and review both product-related and patient-related risk factors that affect its development, and efforts that may be taken to mitigate it. Lastly, we discuss gaps in knowledge and technology and what is needed to fill these. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidemiological aspects of centipede (Scolopendromorphae: Chilopoda bites registered in Greater S. Paulo, SP, Brazil

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Irene Knysak

1998-12-01

Full Text Available INTRODUCTION: The lack of basic knowledge on venomous arthropods and the benignity of the clinical manifestations contribute to the centipede bite victims' not being taken to a treatment reference center, leading to underestimation of the number of cases and minimizing the possibility of a broader epidemiological view. An inventory of the centipede bite occurrences in Greater S. Paulo, Brazil, and the therapeutic methods employed, by the main Brazilian medical center for the notification of poisoning by venomous animals, is presented. METHOD: All patient cards of the period 1980-1989 have been checked as to place, month and time of occurrence; sex, age, affected part of the body, signs and symptoms have been observed, as well as the therapeutic methods employed. The centipedes that caused the accidents were identified at the Arthropods Laboratory. RESULTS: It was registered 216 accidents, with a 69% predominance of the Greater S. Paulo and in only 63% of the cases (136 was the agent brought in by the victim for identification. The genera most frequently represented were Cryptops (58%, Otostigmus (33% and Scolopendra (4%. Of the 136 cases, 87% showed erythema, edema, hemorrhage, burns, cephalalgia, and intense pain. There was a predominance of accidents in the warm rainy season, in the morning and for females between 21 and 60 years of age. Hands and feet were the parts of the body most affected. The benign evolution of the clinical picture (54% made therapeutical treatment unnecessary. Only the victims of Scolopendra and Otostigmus (46% were medicated with anesthetics (51%, analgesics (25%, antihistamines and cortisone (24%. CONCLUSION: The reproductive period of the centipedes, associated with their sinanthropic habits, contributes to the greater incidence of accidents in urban areas in the warm rainy season. Only patients bitten by Scolopendra and Otostigmus require therapeutical treatment.

Therapeutic efficacy of autologous platelet-rich plasma and polydeoxyribonucleotide on female pattern hair loss.

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Lee, Si-Hyung; Zheng, Zhenlong; Kang, Jin-Soo; Kim, Do-Young; Oh, Sang Ho; Cho, Sung Bin

2015-01-01

Autologous platelet-rich plasma (PRP) exerts positive therapeutic effects on hair thickness and density in patients with pattern hair loss. The aim of our study was to evaluate the efficacy of intra-perifollicular autologous PRP and polydeoxyribonucleotide (PDRN) injections in treating female pattern hair loss (FPHL). Twenty FPHL patients were treated with a single session of PRP injection, followed by 12 sessions of PDRN intra-perifollicular injection, along the scalp at weekly intervals. Additionally, another 20 FPHL patients were treated with 12 sessions of PDRN injection only. Meanwhile, one half of the backs of two rabbits was injected with the PRP preparation, while the other half was injected with phosphate buffered saline as a control. Tissue samples from the rabbits were analyzed by real-time polymerase chain reaction and Western blotting. Compared with baseline values, patients treated with PRP and PDRN injections exhibited clinical improvement in mean hair counts (23.2 ± 15.5%; p hair thickness (16.8 ± 10.8%; p hair counts (17.9 ± 13.2%; p hair thickness (13.5 ± 10.7%; p hair thickness than treatment with PDRN therapy alone (p = 0.031), but not in hair counts (p > 0.05). The pilot animal study revealed significant up-regulation of WNT, platelet-derived growth factor, and fibroblast growth factor expression in rabbit skin treated with the PRP preparation, compared with control skin. In conclusion, intra-perifollicular injections of autologous PRP and/or PDRN generate improvements in hair thickness and density in FPHL patients. © 2014 by the Wound Healing Society.

EFFICACY OF IBUPROFEN IN TREATMENT OF PAIN IN CHILDREN: SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED STUDIES

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R.T. Saygitov

2010-01-01

Full Text Available The article presents results of systematic review of data on prophylactic and therapeutic efficacy of ibuprofen. Data search was performed by PubMed database and Google search. 27 publications for analysis were available. Prophylactic efficacy of ibuprofen was studied in 14 studies. Summarizing of the results showed that ibuprofen prevents pain and decreases its following intensity after different surgical or dental operations. There is no significant difference in prophylactic efficacy of single dose ibuprofen and acetaminophen. Therapeutic efficacy of ibuprofen was described in 13 studies. Administration of the drug for pain stopping in children is reasonable. The analgesic effect of ibuprofen compared to placebo was shown in all studies of patients with migraine and diseases of ENT-organs. 5 studies performed in last 5 years showed efficacy of ibuprofen in trauma patients, including children with non-complicated fractures of extremities.Key words: children, pain, ibuprofen, prophylaxis, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(6:52-62

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

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Pengfei Liu

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

Therapeutic efficacy of intralesional 131I-labelled hyaluronectin in grafted human glioblastoma

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Girard, N.; Courel, M.N.; Vera, P.; Delpech, B. [Centre Henri-Becquerel, Rouen (France). Laboratoire d' Oncologie Moleculaire

2000-07-01

The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN). 131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 {mu}Ci/{mu}gHN, 1 {mu}g chloramine-T/{mu}gHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the tumour. On day 4 the radioactivity concentrated in the tumour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 {mu}Ci 131I-HN was injected into the tumour, resulting in a delivery of 6.8 Gy over a 7-day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free 131I or no treatment (six animals per group). Tumour volumes were evaluated every second day from treatment day and the rate of tumour growth was expressed as a ratio of tumour size at time intervals to the tumour size at the time of injection. Growth curves were compared: heat-inactivated with or without free 131I had no anti-tumour effect. Unlabelled HN-injected tumours had a slightly slower growth rate than untreated tumours (p < 0.02) and growth rate of 131I-HN-injected tumours was much lower (p < 0.00002). A pronounced inhibitory effect with intralesional 131I-labelled HN injection resulted from a combination of a) blockage of HA, a proliferation facilitating factor, and b) local irradiation of tumoral tissue, while uptake in normal tissues was minimized.

Therapeutic efficacy of intralesional 131I-labelled hyaluronectin in grafted human glioblastoma

International Nuclear Information System (INIS)

Girard, N.; Courel, M.N.; Vera, P.; Delpech, B.

2000-01-01

The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN). 131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 μCi/μgHN, 1 μg chloramine-T/μgHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the tumour. On day 4 the radioactivity concentrated in the tumour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 μCi 131I-HN was injected into the tumour, resulting in a delivery of 6.8 Gy over a 7-day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free 131I or no treatment (six animals per group). Tumour volumes were evaluated every second day from treatment day and the rate of tumour growth was expressed as a ratio of tumour size at time intervals to the tumour size at the time of injection. Growth curves were compared: heat-inactivated with or without free 131I had no anti-tumour effect. Unlabelled HN-injected tumours had a slightly slower growth rate than untreated tumours (p < 0.02) and growth rate of 131I-HN-injected tumours was much lower (p < 0.00002). A pronounced inhibitory effect with intralesional 131I-labelled HN injection resulted from a combination of a) blockage of HA, a proliferation facilitating factor, and b) local irradiation of tumoral tissue, while uptake in normal tissues was minimized

Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

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Anjaneyulu K

2018-04-01

Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis

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Antonio Lobasso

2017-09-01

Full Text Available BackgroundThyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc. Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4 malabsorption in patients with Hashimoto’s thyroiditis (HT and SSc.Case reportHere, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure.ConclusionA recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

Focus on the therapeutic efficacy of 3BNC117 against HIV-1: In vitro studies, in vivo studies, clinical trials and challenges.

Science.gov (United States)

Liu, Zhi-Jun; Bai, Jing; Liu, Feng-Li; Zhang, Xiang-Yang; Wang, Jing-Zhang

2017-11-01

3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo. The outcomes of Phase I and Phase IIa clinical trials in 2015 and 2016 showed the safety, tolerability, and therapeutic efficacy of 3BNC117 in HIV-1-infected human individuals. Nevertheless, anti-3BNC117 antibodies and HIV-1 strains resistant to 3BNC117 pose clinical challenges to immunotherapy with 3BNC117, so potential strategies for optimizing the potency of 3BNC117 are suggested here. Predictably, HIV-1 prevention and AIDS treatment will benefit from combinational immunotherapies with 3BNC117 and other pharmaceuticals (bNAbs, antiretroviral medicines, viral inducers, etc.) in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

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Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Therapeutic benefits of Nanoparticles in Stroke

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Stavros ePanagiotou

2015-05-01

Full Text Available Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to the brain is restricted by the blood-brain barrier (BBB. Nanoparticles (NPs, which can readily cross the BBB without compromising its integrity, have immense applications in the treatment of ischemic stroke. In this review, potential uses of NPs will be summarized for the treatment of ischemic stroke. Additionally, an overview of targeted NPs will be provided, which could be used in the diagnosis of stroke. Finally, the potential limitations of using NPs in medical applications will be mentioned. Since the use of NPs in stroke therapy is now emerging and is still in development, this review is far from comprehensive or conclusive. Instead, examples of NPs and their current use will be provided, as well as the potentials of NPs in an effort to meet the high demand of new therapies in stroke.

Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy.

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Järnum, Sofia; Runström, Anna; Bockermann, Robert; Winstedt, Lena; Crispin, Max; Kjellman, Christian

2017-09-01

Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887-97. ©2017 AACR . ©2017 American Association for Cancer Research.

A double-blind randomized controlled pilot trial examining the safety and efficacy of therapeutic touch in premature infants.

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Whitley, Julie Anne; Rich, Bonnie L

2008-12-01

To explore the hypothesis that nontouch therapy such as therapeutic touch (TT) reduces stress to a clinically important degree and is safe to use in preterm infants. A pilot randomized, double-blind, controlled trial. Two groups of 10 infants were enrolled and randomly assigned to treatment or nontreatment groups. Gestational age was less than 29 weeks. Demographic descriptions of the 2 groups were statistically similar. The observer and staff were blinded to assignment; the TT practitioner was blinded to observed measurements. Each infant received either TT or no therapeutic touch (NTT) for 5 minutes on 3 consecutive days at the same time of day, behind a curtain. Heart period variability (HPV) was measured 5 minutes before, during, and after the treatment phase. Examination of the parameters of oxygen saturation and episodes of apnea demonstrated no increase in adverse events in TT group compared with NTT group. Repeated-measures multivariate analysis of variance on HPV revealed differences in the interaction of group assignment with low-frequency, high-frequency, and low-to-high- frequency ratio interaction (F2,143 = 8.076, P = .000) and for group, day, and low-frequency, high-frequency, and low-to-high-frequency ratio (F2,288 = 3.146, P = .015), and in the posttreatment time period (F1,16 = 6.259, P = .024), reflective of greater parasympathetic activity in TT group. In this pilot trial, HPV showed an increase for the TT group compared with the NTT group. The study reveals no adverse effects of TT in preterm infants.

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

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Cohan, Stanley

2016-01-01

Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

Therapeutic Uses of Triphala in Ayurvedic Medicine.

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Peterson, Christine Tara; Denniston, Kate; Chopra, Deepak

2017-08-01

The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. A search of the PubMed database was conducted. In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.

Experimental study of plasmapheresis therapeutic efficacy in severe radiation damage

International Nuclear Information System (INIS)

Legeza, V.I.; Abdul', Yu.A.; Chigareva, N.G.; Petkevich, N.V.; Myasoedov, A.F.; Andryukhin, V.I.; Artemenko, A.G.

1994-01-01

In experiments with dogs exposed to 2.9 Gy (LD 80/45 ) it was found that plasmapheresis treatment 4-6 h after irradiation reduce the severity of the radiation sickness clinical manifestations and post-radiation toxemia thus increasing the rate of animal survival up to 60 %. Sham plasmapheresis included all the manipulations of plasmapheretic treatment except plasma substitution and had no detoxication effect and did not affect the irradiated animals survival. This is evidence for leading role of detoxiation in the mechanisms of th therapeutic action of plasmapheresis in acute irradiation

REAL-TIME ASSESSMENT OF MICROWAVE ABLATION EFFICACY BY NIR SPECTROSCOPIC TECHNIQUE

Directory of Open Access Journals (Sweden)

JINZHE ZHAO

2014-01-01

Full Text Available Microwave ablation (MWA status monitoring in real time plays a key role in assessment of therapeutic effectiveness. As a novel real-time assessment method, near infrared spectroscopy (NIRs was used to evaluate the ablation efficacy. MWA experiments were carried out on in vitro porcine livers. An optical measurement system for biological tissue is developed by our lab to monitor reduced scattering coefficient $(\\mu_{s}^{'}$ at 690 nm of the coagulation zones. It is noted that $\\mu_{s}^{'}$ of liver tissue, which increases as the liver tissue being ablated, is clearly related with the coagulation status. $\\mu_{s}^{'}$ of normal tissue and coagulated tissue is 3–5 and 17–19 cm-1, respectively. Continuous changes of $\\mu_{s}^{'}$ demonstrate that optical parameter can be used as an efficacy evaluation factor because it essentially indicates the degree of thermal damage. Compared with temperature, optical parameter is more sensitive and accurate, which is promising for real-time therapeutic efficacy assessment in MWA.

Therapeutic kitchens for residents with dementia.

Science.gov (United States)

Marsden, J P; Meehan, R A; Calkins, M P

2001-01-01

Long-term care facilities are increasingly incorporating some sort of kitchen, often referred to as a therapeutic kitchen, for resident, staff, and family use through remodeling efforts or new construction. A study, consisting of five site visits and a questionnaire mailed to 631 facilities providing dementia care, was conducted to identify physical features that are typically included in therapeutic kitchen design and to explore how these features support daily use in relation to activities programming and food service systems. Findings indicate that universal design features should be incorporated to a greater extent and certain features are more common, reinforce homelike imagery, or enhance safety. Results also suggest that a higher number of residents participate in more recreational activities, such as baking, than they do in household chores, such as meal set-up, and therapeutic kitchens are not always linked to food service systems.

[Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder].

Science.gov (United States)

Zavadenko, N N; Suvorinova, S Iu

2004-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is the most common cause of behavioral and learning problems in childhood. Therapeutic efficiency of nootropil (piracetam) in two different doses has been evaluated in the open control study of 80 children with ADHD, 70 boys and 10 girls, aged 6-11 years, being divided into 3 groups. Two groups received nootropil, as a monotherapy, for a month: 1st group (30 patients)--in the dosage of 70 mg/kg daily and 2nd group (30 patients)--40 mg/kg daily orally. The control group of 20 patients did not receive any treatment. All children were examined twice with one month interval. A procedure of assessment included of structured questionnaire to parents, neurological examination with scored evaluation of subtle signs and psychological testing. Nootropil therapy in ADHD children resulted in the improvement of behavioral characteristics, motor coordination as well as continuous, selective and divided attention. A response rate was 60% in patients received 70 mg/kg of nootropil and 43% for nootropil dosage of 40 mg/kg. The results of the study suggest more considerable positive therapeutic effects of nootropil higher dose on behavioral, motor and attention characteristics in children with ADHD.

Efficacy methods to evaluate health communication and marketing campaigns.

Science.gov (United States)

Evans, W Douglas; Uhrig, Jennifer; Davis, Kevin; McCormack, Lauren

2009-06-01

Communication and marketing are growing areas of health research, but relatively few rigorous efficacy studies have been conducted in these fields. In this article, we review recent health communication and marketing efficacy research, present two case studies that illustrate some of the considerations in making efficacy design choices, and advocate for greater emphasis on rigorous health communication and marketing efficacy research and the development of a research agenda. Much of the outcomes research in health communication and marketing, especially mass media, utilizes effectiveness designs conducted in real time, in the media markets or communities in which messages are delivered. Such evaluations may be impractical or impossible, however, imiting opportunities to advance the state of health communication and marketing research and the knowledge base on effective campaign strategies, messages, and channels. Efficacy and effectiveness studies use similar measures of behavior change. Efficacy studies, however, offer greater opportunities for experimental control, message exposure, and testing of health communication and marketing theory. By examining the literature and two in-depth case studies, we identify advantages and limitations to efficacy studies. We also identify considerations for when to adopt efficacy and effectiveness methods, alone or in combination. Finally, we outline a research agenda to investigate issues of internal and external validity, mode of message presentation, differences between marketing and message strategies, and behavioral outcomes.

Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

Science.gov (United States)

Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

1999-03-01

We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

Directory of Open Access Journals (Sweden)

Katsuya Endo

2016-01-01

Full Text Available Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC. Although some studies have compared the efficacy of infliximab (IFX and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac. This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX (n=48 or Tac (n=47 in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p<0.001; log-rank test. The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

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Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

Promoting Efficacy Research on Functional Analytic Psychotherapy

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Maitland, Daniel W. M.; Gaynor, Scott T.

2012-01-01

Functional Analytic Psychotherapy (FAP) is a form of therapy grounded in behavioral principles that utilizes therapist reactions to shape target behavior. Despite a growing literature base, there is a paucity of research to establish the efficacy of FAP. As a general approach to psychotherapy, and how the therapeutic relationship produces change,…

Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

Science.gov (United States)

Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

2017-01-01

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Therapeutic drug monitoring of infliximab : performance evaluation of three commercial ELISA kits

NARCIS (Netherlands)

Schmitz, E.M.H.; van de Kerkhof, D.; Hamann, D.; van Dongen, J.L.J.; Kuijper, P.H.M.; Brunsveld, L.; Scharnhorst, V.; Broeren, M.A.C.

2016-01-01

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences

Comparative evaluation of therapeutic efficacy of sulfadiazine-trimethoprim, oxytetracycline, enrofloxacin and florfenicol on Staphylococcus aureus-induced arthritis in broilers.

Science.gov (United States)

Mosleh, N; Shomali, T; Namazi, F; Marzban, M; Mohammadi, M; Boroojeni, A Motamedi

2016-04-01

Staphylococcus aureus is an important human and veterinary pathogen that causes economic loss in the poultry industry. This study aimed to compare therapeutic efficacy of 4 commonly used antibiotics in poultry on S. aureus-induced arthritis in broilers. Sixty broilers, 8 weeks of age, were assigned at random into 7 groups as follows: (1) negative control (n = 5); (2) vehicle control (n = 5); (3) sulfadiazine-trimethoprim, 250 ml/1000 l drinking water (n = 10); (4) oxytetracycline 20%, 1 mg/l drinking water (n = 10); (5) florfenicol 10%, 1/1000 v/v in drinking water (n = 10); (6) enrofloxacin 10%, 1/1000 v/v in drinking water (n = 10) and (7) positive control (n = 10). Birds in group 2 were injected with 1 ml of sterile TSB medium into the right tibiotarsal joint on d 0 while other birds (except group 1) were challenged with 1 ml of 1.2 × 10(10) CFU/ml suspension of S. aureus bacteria. Antibiotic therapy was started from d 4 post challenge and continued for 5 d. At the end, birds were weighed and clinical severity of arthritis was determined. After blood collection, birds were slaughtered and tibiotarsal and hip joints were evaluated grossly. The content of inflammatory exudates of tibiotarsal joint and the degree of femoral head necrosis were recorded. Mucin clot test and histopathological evaluation were performed on right tibiotarsal joint. Serum interleukin 6 was also assayed. Sulfadiazine-trimethoprim had higher therapeutic efficiency with regard to most of the assayed criteria, whereas none of the antibiotics significantly affected femoral head necrosis and body weight. These data will help clinicians to have better antibiotic choice in field conditions.

Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease

OpenAIRE

Cayatte, Corinne; Joyce-Shaikh, Barbara; Vega, Felix; Boniface, Katia; Grein, Jeffrey; Murphy, Erin; Blumenschein, Wendy M; Chen, Smiley; Malinao, Maria-Christina; Basham, Beth; Pierce, Robert H; Bowman, Edward P; McKenzie, Brent S; Elson, Charles O; Faubion, William A

2012-01-01

OBJECTIVES: Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). METHODS: Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-...

Glycosylation profiles of therapeutic antibody pharmaceuticals.

Science.gov (United States)

Wacker, Christoph; Berger, Christoph N; Girard, Philippe; Meier, Roger

2011-11-01

Recombinant antibodies specific for human targets are often used as therapeutics and represent a major class of drug products. Their therapeutic efficacy depends on the formation of antibody complexes resulting in the elimination of a target molecule or the modulation of specific signalling pathways. The physiological effects of antibody therapeutics are known to depend on the structural characteristics of the antibody molecule, specifically on the glycosylation which is the result of posttranslational modifications. Hence, production of therapeutic antibodies with a defined and consistent glycoform profile is needed which still remains a considerable challenge to the biopharmaceutical industry. To provide an insight into the industries capability to control their manufacturing process and to provide antibodies of highest quality, we conducted a market surveillance study and compared major oligosaccharide profiles of a number of monoclonal antibody pharmaceuticals sampled on the Swiss market. Product lot-to-lot variability was found to be generally low, suggesting that a majority of manufacturers have implemented high quality standards in their production processes. However, proportions of G0, G1 and G2 core-fucosylated chains derived from different products varied considerably and showed a bias towards the immature agalactosidated G0 form. Interestingly, differences in glycosylation caused by the production cell type seem to be of less importance compared with process related parameters such as cell growth. Copyright © 2011 Elsevier B.V. All rights reserved.

The Therapeutic Alliance and Family Psychoeducation in the Treatment of Schizophrenia: An Exploratory Prospective Change Process Study

Science.gov (United States)

Smerud, Phyllis E.; Rosenfarb, Irwin S.

2008-01-01

Although family psychoeducation has been shown to be highly efficacious in the treatment of schizophrenia, the mechanisms underlying the treatment's success are poorly understood. The therapeutic alliance in behavioral family management (BFM) was examined to determine whether the alliance plays a role in the efficacy of this treatment. One early…

Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system.

Science.gov (United States)

Hu, Mei; Zhang, Jinjie; Ding, Rui; Fu, Yao; Gong, Tao; Zhang, Zhirong

2017-04-01

The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus ® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2-2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.

Therapeutic genes for anti-HIV/AIDS gene therapy.

Science.gov (United States)

Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

2013-01-01

The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-04-15

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

[Therapeutic response of Plasmodium vivax to chloroquine in Bolivia].

Science.gov (United States)

Añez, Arletta; Navarro-Costa, Dennis; Yucra, Omar; Garnica, Cecilia; Melgar, Viviana; Moscoso, Manuel; Arteaga, Ricardo; Nakao, Gladys

2012-01-01

Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.

Determinants of immunogenic response to protein therapeutics.

Science.gov (United States)

Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

2012-09-01

Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

Hospitals with greater diversities of physiologically complex procedures do not achieve greater surgical growth in a market with stable numbers of such procedures.

Science.gov (United States)

Dexter, Franklin; Epstein, Richard H; Lubarsky, David A

2018-05-01

Although having a large diversity of types of procedures has a substantial operational impact on the surgical suites of hospitals, the strategic importance is unknown. In the current study, we used longitudinal data for all hospitals and patient ages in the State of Florida to evaluate whether hospitals with greater diversity of types of physiologically complex major therapeutic procedures (PCMTP) also had greater rates of surgical growth. Observational cohort study. 1479 combinations of hospitals in the State of Florida and fiscal years, 2008-2015. The types of International Classification of Diseases, Ninth revision, Clinical Modification (ICD-9-CM) procedures studied were PCMT, defined as: a) major therapeutic procedure; b) >7 American Society of Anesthesiologists base units; and c) performed during a hospitalization with a Diagnosis Related Group with a mean length of stay ≥4.0days. The number of procedures of each type of PCMTP commonly performed at each hospital was calculated by taking 1/Herfindahl index (i.e., sum of the squares of the proportions of all procedures of each type of PCMTP). Over the 8 successive years studied, there was no change in the number of PCMTP being performed (Kendall's τ b =-0.014±0.017 [standard error], P=0.44; N=1479 hospital×years). Busier and larger hospitals commonly performed more types of PCMTP, respectively categorized based on performed PCMTP (τ=0.606±0.017, P<0.0001) or hospital beds (τ=0.524±0.017, P<0.0001). There was no association between greater diversity of types of PCMTP commonly performed and greater annual growth in numbers of PCMTP (τ=0.002±0.019, P=0.91; N=1295 hospital×years). Conclusions were the same with multiple sensitivity analyses. Post hoc, it was recognized that hospitals performing a greater diversity of PCMTP were more similar to the aggregate of other hospitals within the same health district (τ=0.550±0.017, P<0.0001). During a period with no overall growth in PCMTP, hospitals with

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

Science.gov (United States)

Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

2017-12-01

Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

Preclinical models used for immunogenicity prediction of therapeutic proteins.

Science.gov (United States)

Brinks, Vera; Weinbuch, Daniel; Baker, Matthew; Dean, Yann; Stas, Philippe; Kostense, Stefan; Rup, Bonita; Jiskoot, Wim

2013-07-01

All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.

Potential Therapeutic Effects of Psilocybin.

Science.gov (United States)

Johnson, Matthew W; Griffiths, Roland R

2017-07-01

Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

Avian Diagnostic and Therapeutic Antibodies

Energy Technology Data Exchange (ETDEWEB)

Bradley, David Sherman [UND SMHS

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.

Short-term therapeutic effects of combined therapy with metformin hydrochloride for aplastic anemia

Directory of Open Access Journals (Sweden)

Xue-chun LU

2012-03-01

Full Text Available Objective　To screen and select new drugs for aplastic anemia (AA and evaluate their clinical efficacy by clinical bioinformatics methods. Methods　First, we established genome expression profiles of AA patients, and conducted similarity analyses with the pharmacogenomics database to screen and select drugs with possible efficacy. Intractable AA patients who received immunosuppressors and/or androgen for more than six months showing no clinical efficacy were enrolled in the study to evaluate therapeutic effects of the therapeutic regime. Clinical efficacy and adverse effects were evaluated after six months. Results　The clinical bioinformatics results showed therapeutic effects of metformin hydrochloride on AA. Forty-three intractable AA patients (15 with severe AA were treated with metformin hydrochloride combined with cyclosporin A (CsA and stanozolol. Twenty-seven transfusion-dependent patients (100% became transfusion independent after a 6-month therapy. The hemoglobin level completely returned to normal in 37 out of 40 anemia patients (92.5%. In the 40 patients with platelet count lower than 20×109/L, the platelet count of 28 patients (90.3% increased to higher than 50×109/L. The white cell count increased to higher than 3.5×109/L in 30 out of 35 patients (88.6% with white cell count lower than 2.5×109/L. Among 40 anemic patients, 1 was found to have abnormal renal function, but it recovered to the normal range after ending CsA treatment. Eighteen patients were found to have elevated transaminase levels which were lowered to normal range after using liver protectants and reducing the dosage of stanozolol. There were no instances of hypoglycemia in all patients throughout the treatment. Conclusion　Combination of metformin hydrochloride, CsA and stanozolol is effective in refractory aplastic anemia with acceptable toxicity.

ePrescribing: Reducing Costs through In-Class Therapeutic Interchange.

Science.gov (United States)

Stenner, Shane P; Chakravarthy, Rohini; Johnson, Kevin B; Miller, William L; Olson, Julie; Wickizer, Marleen; Johnson, Nate N; Ohmer, Rick; Uskavitch, David R; Bernard, Gordon R; Neal, Erin B; Lehmann, Christoph U

2016-12-14

Spending on pharmaceuticals in the US reached $373.9 billion in 2014. Therapeutic interchange offers potential medication cost savings by replacing a prescribed drug for an equally efficacious therapeutic alternative. Hard-stop therapeutic interchange recommendation alerts were developed for four medication classes (HMG-CoA reductase inhibitors, serotonin receptor agonists, intranasal steroid sprays, and proton-pump inhibitors) in an electronic prescription-writing tool for outpatient prescriptions. Using prescription data from January 2012 to June 2015, the Compliance Ratio (CR) was calculated by dividing the number of prescriptions with recommended therapeutic interchange medications by the number of prescriptions with non-recommended medications to measure effectiveness. To explore potential cost savings, prescription data and medication costs were analyzed for the 45,000 Vanderbilt Employee Health Plan members. For all medication classes, significant improvements were demonstrated - the CR improved (proton-pump inhibitors 2.8 to 5.32, nasal steroids 2.44 to 8.16, statins 2.06 to 5.51, and serotonin receptor agonists 0.8 to 1.52). Quarterly savings through the four therapeutic interchange interventions combined exceeded $200,000 with an estimated annual savings for the health plan of $800,000, or more than $17 per member. A therapeutic interchange clinical decision support tool at the point of prescribing resulted in increased compliance with recommendations for outpatient prescriptions while producing substantial cost savings to the Vanderbilt Employee Health Plan - $17.77 per member per year. Therapeutic interchange rules require rational targeting, appropriate governance, and vigilant content updates.

Clinical efficacy of bromocriptine and the influence of serum ...

African Journals Online (AJOL)

Background: Psoriasis is a T-cell mediated hyperproliferative cutaneous disease of multifactorial etiology. Prolactin (PRL) has been implicated in the pathogenesis of psoriasis and several studies have pointed to a potential therapeutic role of bromocriptine in psoriasis. Aim: To assess the clinical efficacy of bromocriptine ...

Multivalent Soluble Antigen Arrays Exhibit High Avidity Binding and Modulation of B Cell Receptor-Mediated Signaling to Drive Efficacy against Experimental Autoimmune Encephalomyelitis.

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Hartwell, Brittany L; Pickens, Chad J; Leon, Martin; Berkland, Cory

2017-06-12

A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgA PLP:LABL ), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgA PLP:LABL , employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro. Our results pointed to sustained BCR engagement as the SAgA PLP:LABL therapeutic mechanism, so we developed a new version of the SAgA molecule using nonhydrolyzable conjugation chemistry, hypothesizing it would enhance and maintain the molecule's action at the cell surface to improve efficacy. "Click SAgA" (cSAgA PLP:LABL ) uses hydrolytically stable covalent conjugation chemistry (Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC)) rather than a hydrolyzable oxime bond to attach PLP and LABL to HA. We explored cSAgA PLP:LABL B cell engagement and modulation of BCR-mediated signaling in vitro through flow cytometry binding and calcium flux signaling assays. Indeed, cSAgA PLP:LABL exhibited higher avidity B cell binding and greater dampening of BCR-mediated signaling than hydrolyzable SAgA PLP:LABL . Furthermore, cSAgA PLP:LABL exhibited significantly enhanced in vivo efficacy compared to hydrolyzable SAgA PLP:LABL , achieving equivalent efficacy at one-quarter of the dose. These results indicate that nonhydrolyzable conjugation increased the avidity of cSAgA PLP:LABL to drive in vivo efficacy through modulated BCR-mediated signaling.

Efficacy of prophylactic irradiation in altering renal allograft survival

International Nuclear Information System (INIS)

Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.

1974-01-01

Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids

Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

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Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

2014-01-01

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

Pharmacokinetic profile of voriconazole in a critically ill patient on therapeutic plasma exchange

NARCIS (Netherlands)

Spriet, I.; Bruggemann, R.J.M.; Annaert, P.; Meersseman, P.; Wijngaerden, E. van; Lagrou, K.; Willems, L.

2013-01-01

BACKGROUND: Extracorporeal removal of drugs during therapeutic plasma exchange (TPE) can lead to decreased efficacy, as shown in several reports discussing altered pharmacokinetics (PKs) of antibiotics during TPE. In particular, drugs with a low volume of distribution or a high protein binding are

Comparison of Therapeutic Efficacies of Norethisterone, Tranexamic Acid and Levonorgestrel-Releasing Intrauterine System for the Treatment of Heavy Menstrual Bleeding: A Randomized Controlled Study.

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Kiseli, Mine; Kayikcioglu, Fulya; Evliyaoglu, Ozlem; Haberal, Ali

2016-01-01

Our aim was to compare the therapeutic efficacies of norethisterone acid (NETA), tranexamic acid and levonorgestrel-releasing intrauterine system (LNG-IUS) in treating idiopathic heavy menstrual bleeding (HMB). Women with heavy uterine bleeding were randomized to receive NETA, tranexamic acid or LNG-IUS for 6 months. The primary outcome was a decrease in menstrual bleeding as assessed by pictorial blood loss assessment charts and hematological parameters analyzed at the 1st, 3rd and 6th months. Health-related quality of life (QOL) variables were also recorded and analyzed. Twenty-eight patients were enrolled in each treatment group, but the results of only 62 were evaluated. NETA, tranexamic acid, and LNG-IUS reduced menstrual blood loss (MBL) by 53.1, 60.8, and 85.8%, respectively, at the 6th month. LNG-IUS was more effective than NETA and tranexamic acid in decreasing MBL. LNG-IUS was also more efficient than tranexamic acid in correcting anemia related to menorrhagia. Satisfaction rates were comparable among the NETA (70%), tranexamic acid (63%) and LNG-IUS (77%) groups. QOL in physical aspects increased significantly in the tranexamic acid and LNG-IUS groups. The positive effect of LNG-IUS on QOL parameters, as well as its high efficacy, makes it a first-line option for HMB. © 2016 S. Karger AG, Basel.

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

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Monir Moradzadeh Khiavi

2015-06-01

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

An exploratory examination of patient and parental self-efficacy as predictors of weight gain in adolescents with anorexia nervosa.

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Byrne, Catherine E; Accurso, Erin C; Arnow, Katherine D; Lock, James; Le Grange, Daniel

2015-11-01

To determine whether increases in adolescent or parental self-efficacy predicted subsequent weight gain in two different therapies for adolescent anorexia nervosa (AN). Participants were 121 adolescents with AN (M = 14.4 years, SD = 1.6), from a two-site randomized clinical trial for family-based treatment (FBT) and individual adolescent focused therapy (AFT). Both adolescent and parental self-efficacy were assessed at baseline and sessions 2, 4, 6, and 8. Adolescent self-efficacy was assessed using a generic measure of self-efficacy, while parental self-efficacy was assessed using a measure specific to the recovery of an eating disorder. Weight was assessed at baseline, sessions 1 through 8, and end of treatment. Mixed-effects models were used to evaluate the relation between patient and parent self-efficacy and subsequent weight gain, controlling for weight at the previous time point. For families who received FBT, greater within-treatment increases in parental self-efficacy predicted greater subsequent adolescent weight gain compared to those who received FBT with lesser change in parental self-efficacy and those who received AFT. Interestingly, adolescent self-efficacy did not significantly predict subsequent weight gain. Greater increases in parental self-efficacy predicted significantly greater subsequent weight gain for adolescents who received FBT, but the same was not true for adolescents who received AFT. Neither overall level nor change in adolescent self-efficacy significantly predicted subsequent weight gain in either treatment group. These findings emphasize the importance of increasing parental self-efficacy in FBT in order to impact adolescent weight outcomes. © 2015 Wiley Periodicals, Inc.

Optimization of ultrasound parameters of myocardial cavitation microlesions for therapeutic application.

Science.gov (United States)

Miller, Douglas L; Dou, Chunyan; Owens, Gabe E; Kripfgans, Oliver D

2014-06-01

Intermittent high intensity ultrasound scanning with contrast microbubbles can induce scattered cavitation microlesions in the myocardium, which may be of value for tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5 MHz focused ultrasound pulses, guided by an 8 MHz imaging transducer. The relative efficacy with 2 or 4 MPa pulses, 1:4 or 1:8 trigger intervals and 5 or 10 cycle pulses was explored in six groups. Electrocardiogram premature complexes (PCs) induced by the triggered pulse bursts were counted, and Evans blue stained cardiomyocyte scores (SCSs) were obtained. The increase from 2 to 4 MPa produced significant increases in PCs and SCSs and eliminated an anticipated decline in the rate of PC induction with time, which might hinder therapeutic efficacy. Increased intervals and pulse durations did not yield significant increases in the effects. The results suggest that cavitation microlesion production can be refined and potentially lead to a clinically robust therapeutic method. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Psychometric Properties of an Instrument Derived from the Intentional Relationship Model: The SelfEfficacy for Recognizing Clients’ Interpersonal Characteristics (N-SERIC

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Victoria C. Ritter

2018-04-01

Full Text Available Background: The Intentional Relationship Model conceptualizes the therapeutic use of self in occupational therapy. To increase motivation for and success in establishing therapeutic relationships, therapists need self-efficacy for using the self in therapeutic practice. However, attempts to combine this model with self-efficacy theory are rare, and instruments by which to measure self-efficacy for therapeutic use of self are in a developing stage. This study aimed to examine the factor structure and internal consistency of the Norwegian Self-Efficacy for Recognizing Interpersonal Characteristics (N-SERIC. Methods: Occupational therapy students (n = 100 from two education programs completed the instrument and sociodemographic information. The factor structure was examined with Principal Components Analysis (PCA, and internal consistency was assessed with Cronbach’s α and inter-item correlations. Results: The PCA revealed that all N-SERIC items belonged to the same latent factor, with factor loadings ranging between 0.75 and 0.89. The internal consistency of the scale items was high (Cronbach’s α = 0.96. Conclusions: The N-SERIC scale is unidimensional and the items have very high internal consistency. Thus, the scale sum score can be useful for occupational therapy research and audits focusing on interpersonal aspects of practice.

Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF.

Science.gov (United States)

Yatuv, Rivka; Robinson, Micah; Dayan, Inbal; Baru, Moshe

2010-02-01

Improving the pharmacodynamics of protein drugs has the potential to improve the care and the quality of life of patients suffering from a variety of diseases. Four approaches to improve protein drugs are described: PEGylation, amino acid substitution, fusion to carrier proteins and encapsulation. A new platform technology based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip) is then presented. Binding of proteins to PEGLip is non-covalent, highly specific and dependent on an amino acid consensus sequence within the proteins. Association of proteins with PEGLip results in substantial enhancement of the pharmacodynamic properties of proteins following administration. This has been demonstrated in preclinical studies and clinical trials with coagulation factors VIII and VIIa. It has also been demonstrated in preclinical studies with granulocyte colony-stimulating factor. A mechanism is presented that explains the improvements in hemostatic efficacy of PEGLip-formulated coagulation factors VIII and VIIa. The reader will gain an understanding of the advantages and disadvantages of each of the approaches discussed. PEGLip formulation is an important new approach to improve the pharmacodynamics of protein drugs. This approach may be applied to further therapeutic proteins in the future.

Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

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Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

2004-01-01

To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

Efficacy of various single-dose regimens of ceftriaxone in ...

African Journals Online (AJOL)

The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

Science.gov (United States)

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

2016-03-17

The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

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

Science.gov (United States)

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

2015-07-01

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

Efficacy and pharmacokinetics of intravenous paracetamol in the critically ill patient

NARCIS (Netherlands)

Samson, A.D.; Hunfeld, N.G.; Touw, D.J.; Melief, P.H.

2009-01-01

Introduction: Paracetamol (PCM) is a drug with analgesic and antipyretic properties. Despite its frequent use, little is known about its efficacy and pharmacokinetics (PK) when intravenously administered in the critically ill patient. A previous study suggests that therapeutic concentrations are not

Short-Term Therapeutic Efficacy of the Isobar TTL Dynamic Internal Fixation System for the Treatment of Lumbar Degenerative Disc Diseases.

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Qian, Jiale; Bao, Zhaohua; Li, Xuefeng; Zou, Jun; Yang, Huilin

2016-07-01

At present, posterior interbody fusion surgery with pedicle internal fixation is the gold standard for the treatment of lumbar degenerative disc diseases. However, an increasing number of studies have shown that because fused lumbar vertebrae lose their physiological activity, the compensatory range of motion (ROM) of the adjacent levels increases. To address this issue, dynamic internal fixation systems have been developed. Our goal was to investigate the short-term therapeutic efficacy of the Isobar TTL dynamic internal fixation system for the treatment of lumbar degenerative disc diseases and its effect on the ROM of the surgical segments. Retrospective Evaluation. Tertiary hospital setting in China. Twenty-four lumbar degenerative disc disease patients who underwent posterior lumbar decompression and single-segment Isobar TTL dynamic internal fixation at our hospital between January 2013 and July 2014 were retrospectively analyzed. The preoperative and one month, 3 month, and 12 month postoperative visual analog scale (VAS) pain scores, Japanese Orthopedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores were observed and recorded to assess the clinical therapeutic effect; the lumbar ROM was measured preoperatively and at the last follow-up to evaluate the preservation of functional movement in the dynamically stabilized segment. All patients underwent the operation successfully without complications during hospitalization and were followed for 12 to 27 months, with an average of 18 months. The patients' preoperative and one month, 3 month, and 12 month postoperative VAS scores were 6.42 ± 0.72, 1.71 ± 0.86, 1.38 ± 0.65, and 1.37 ± 0.58, respectively, and their JOA scores were 9.54 ± 1.89, 21.21 ± 1.98, 22.50 ± 1.47, and 23.46 ± 1.32, respectively. The preoperative ODI score was 42.04 ± 2.63; the one month, 3 month, and 12 month postoperative ODI scores were 22.79 ± 1.61, 18.63 ± 1.61, and 15.08 ± 1.21, respectively. These

[Self-stigma, self-esteem and self-efficacy of mentally ill].

Science.gov (United States)

Pasmatzi, E; Koulierakis, G; Giaglis, G

2016-01-01

The way that the social stigma of mental illness is related with the self-stigma, which in turn affects self-esteem and self-efficacy of mental patients was investigated. A sample of 66 patients in the Adult Psychiatric Clinic of the Thessaloniki General Hospital "G. Papanikolaou" was participated in this descriptive association study, with cross-sectional comparisons. The sample comprised of patients who were hospitalized or visited the Clinic as out-patients during the period that the study was undertaken. A tool for measuring the basic demographic, social and clinical characteristics of the participants was designed and used. Additionally, the Self-Stigma of Mental Illness Scale, SSMIS, Rosenberg's Self-Esteem Scale, RSE and the General Self-Efficacy Sherer Scale, GSESH were used for measuring self-stigma, self-esteem and self-efficacy respectively. Results showed that self-esteem and self-efficacy were highly associated with each another. Self-esteem and self-efficacy co varied. Greater self-stigma was associated with lower self-esteem and selfefficacy confirming the power of this relationship which is connected with patients' psychological empowerment and acts as mediator between patients' self-categorization as "mentally ill" and their self-esteem and self-efficacy. Additionally, a mild negative association between self-esteem, self-efficacy and age was found while higher educational level was associated with greater selfefficacy. Greater self-stigma along with lower educational level were the most significant predictors of both self-esteem and self-efficacy of mental patients, as shown by regression analysis. Some of our results, such as the percentage of low self-esteem (30.3%), were different from previous relevant data (9.1-24%), probably due to differences in sample's cultural characteristics and composition, research tools used, and the degree of mentally ill patients' reaction to social stigma perception. Despite its methodological limitations, the

[The development of therapeutic vaccine for hepatitis C virus].

Science.gov (United States)

Kimura, Kiminori; Kohara, Michinori

2012-10-01

Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.

Development of CAR T cells designed to improve antitumor efficacy and safety

OpenAIRE

Jaspers, Janneke E.; Brentjens, Renier J.

2017-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how ...

Engineering Specificity and Function of Therapeutic Regulatory T Cells

Directory of Open Access Journals (Sweden)

Jenny L. McGovern

2017-11-01

Full Text Available Adoptive therapy with polyclonal regulatory T cells (Tregs has shown efficacy in suppressing detrimental immune responses in experimental models of autoimmunity and transplantation. The lack of specificity is a potential limitation of Treg therapy, as studies in mice have demonstrated that specificity can enhance the therapeutic potency of Treg. We will discuss that vectors encoding T cell receptors or chimeric antigen receptors provide an efficient gene-transfer platform to reliably produce Tregs of defined antigen specificity, thus overcoming the considerable difficulties of isolating low-frequency, antigen-specific cells that may be present in the natural Treg repertoire. The recent observations that Tregs can polarize into distinct lineages similar to the Th1, Th2, and Th17 subsets described for conventional T helper cells raise the possibility that Th1-, Th2-, and Th17-driven pathology may require matching Treg subsets for optimal therapeutic efficacy. In the future, genetic engineering may serve not only to enforce FoxP3 expression and a stable Treg phenotype but it may also enable the expression of particular transcription factors that drive differentiation into defined Treg subsets. Together, established and recently developed gene transfer and editing tools provide exciting opportunities to produce tailor-made antigen-specific Treg products with defined functional activities.

Production Methods for a Mesenchymal Stem Cell Therapeutic as a Medical Defense Countermeasure

Science.gov (United States)

2012-02-01

mesenchymal stem cell (MSC) efficacy in a variety of injury models demonstrate the unique qualities of this reparative cell population to adapt to the...therapeutic product. Characterization of stem cell properties of culture-expanded MSCs is shown by in vitro differentiation to form mature cell types. The

Therapeutic enhancement of protective immunity during experimental leishmaniasis.

Directory of Open Access Journals (Sweden)

Senad Divanovic

2011-09-01

Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

Science.gov (United States)

Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

2001-08-01

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination

Vicarious and Persuasive Influences on Efficacy Expectations and Intentions To Perform Breast Self-Examination.

Science.gov (United States)

Anderson, Ronald B.

2000-01-01

Tests the impact of symbolic modeling and persuasive efficacy information on self-efficacy beliefs and intentions to perform breast self-examinations among 147 undergraduate students. Assesses the effects of these modes of efficacy induction on fear arousal and response-outcome expectations. Finds symbolic modeling engendered greater efficacy…

Identification of the factors that govern the ability of therapeutic antibodies to provide postchallenge protection against botulinum toxin: a model for assessing postchallenge efficacy of medical countermeasures against agents of bioterrorism and biological warfare.

Science.gov (United States)

Al-Saleem, Fetweh H; Nasser, Zidoon; Olson, Rebecca M; Cao, Linsen; Simpson, Lance L

2011-08-01

Therapeutic antibodies are one of the major classes of medical countermeasures that can provide protection against potential bioweapons such as botulinum toxin. Although a broad array of antibodies are being evaluated for their ability to neutralize the toxin, there is little information that defines the circumstances under which these antibodies can be used. In the present study, an effort was made to quantify the temporal factors that govern therapeutic antibody use in a postchallenge scenario. Experiments were done involving inhalation administration of toxin to mice, intravenous administration to mice, and direct application to murine phrenic nerve-hemidiaphragm preparations. As part of this study, several pharmacokinetic characteristics of botulinum toxin and neutralizing antibodies were measured. The core observation that emerged from the work was that the window of opportunity within which postchallenge administration of antibodies exerted a beneficial effect increased as the challenge dose of toxin decreased. The critical factor in establishing the window of opportunity was the amount of time needed for fractional redistribution of a neuroparalytic quantum of toxin from the extraneuronal space to the intraneuronal space. This redistribution event was a dose-dependent phenomenon. It is likely that the approach used to identify the factors that govern postchallenge efficacy of antibodies against botulinum toxin can be used to assess the factors that govern postchallenge efficacy of medical countermeasures against any agent of bioterrorism or biological warfare.

Efficacy and enlightenment: LSD psychotherapy and the Drug Amendments of 1962.

Science.gov (United States)

Oram, Matthew

2014-04-01

The decline in therapeutic research with lysergic acid diethylamide (LSD) in the United States over the course of the 1960s has commonly been attributed to the growing controversy surrounding its recreational use. However, research difficulties played an equal role in LSD psychotherapy's demise, as they frustrated researchers' efforts to clearly establish the efficacy of treatment. Once the Kefauver Harris Drug Amendments of 1962 introduced the requirement that proof of efficacy be established through controlled clinical trials before a drug could be approved to market, the value of clinical research became increasingly dependent on the scientific rigor of the trial's design. LSD psychotherapy's complex method of utilizing drug effects to catalyze a psychological treatment clashed with the controlled trial methodology on both theoretical and practical levels, making proof of efficacy difficult to obtain. Through a close examination of clinical trials performed after 1962, this article explores how the new emphasis on controlled clinical trials frustrated the progress of LSD psychotherapy research by focusing researchers' attention on trial design to the detriment of their therapeutic method. This analysis provides a new perspective on the death of LSD psychotherapy and explores the implications of the Drug Amendments of 1962.

Efficacy of various single-dose regimens of ceftriaxone in ...

African Journals Online (AJOL)

1990-08-18

Aug 18, 1990 ... The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), admini- stered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg.

Characterization of the pharmacokinetics, brain distribution, and therapeutic efficacy of the adenosine A1 receptor partial agonist 2'-deoxy-N6-cyclopentyladenosine in sarin-poisoned rats

International Nuclear Information System (INIS)

Bueters, Tjerk J.H.; IJzerman, Ad P.; Helden, Herman P.M. van; Danhof, Meindert

2003-01-01

Characterization of the pharmacokinetics, brain distribution, and therapeutic efficacy of the adenosine A 1 receptor partial agonist 2'-deoxy-N 6 -cyclopentyladenosine in sarin-poisoned rats. Bueters, T.J.H., IJzerman, A.P., Van Helden, H.P.M., and Danhof, M. (2003). The objective of the present study was to determine (1) the influence of sarin poisoning (144 μg/kg sc) on the pharmacokinetics and brain distribution of the adenosine A 1 receptor partial agonist 2'-deoxy-N 6 -cyclopentyladenosine (2'dCPA), and (2) the effect of 2'dCPA (20 mg/kg iv) on the central acetylcholine (ACh) release and protection against sarin toxicity. A five-compartment model successfully described the pharmacokinetic profile of 2'dCPA in blood and brain microdialysate. A covariate analysis revealed that the volume of distribution of 2'dCPA in blood was different in sarin-poisoned rats, 177 ± 7 versus 148 ± 8 ml in control rats. However, the transport of 2'dCPA from blood to the brain was unaffected as reflected by the values of the intercompartmental transport clearances, 0.21 ± 0.02 and 0.21 ± 0.04 μl/min in control and sarin-poisoned rats, respectively. Also the area-under-curve (AUC) ratios of brain microdialysate and blood were identical with values of 0.02 ± 0.001 and 0.02 ± 0.002, respectively, demonstrating the restricted transport of 2'dCPA into the brain in both treatment groups. Treatment of sarin-poisoned rats by 2'dCPA did not adequately prevent the accumulation of ACh in the central nervous system. 2'dCPA delayed the emergence of concomitant symptoms compared to untreated rats, but eventually only 29% of the animals survived 24 h. In conclusion, the pharmacokinetic profile of 2'dCPA in blood was slightly changed by sarin, but not the distribution of 2'dCPA into the brain. The therapeutic efficacy of 2'dCPA against sarin was limited, presumably due to insufficient quantities of 2'dCPA reaching the brain

Pharmacogenetics approach to therapeutics.

Science.gov (United States)

Koo, Seok Hwee; Lee, Edmund Jon Deoon

2006-01-01

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

Efficacy of comprehensive treatment on amblyopia in 255 children

Directory of Open Access Journals (Sweden)

Xing-Hui Xu

2015-11-01

Full Text Available AIM: To study the efficacy of comprehensive treatment on amblyopia in children.METHODS: A total of 255 cases 386 eyes diagnosed as amblyopia were given refractive errors correction, multi-media training system, coveting treatment, CAM treatment and red light stimulation. The relationship of therapeutic effect with age, type and degree of amblyopia was analyzed. RESULTS: The total effective rate was 94%, and total cure rate was 71%. Mild amblyopia, 3～6 years group, ametropia amblyopia had the highest cure rate. CONCLUSION: Efficacy of comprehensive treatment on amblyopia is certain, which is relation with age, type and degree of amblyopia.

Recent Advances in Stem Cell-Based Therapeutics for Stroke

OpenAIRE

Napoli, Eleonora; Borlongan, Cesar V.

2016-01-01

Regenerative medicine for central nervous system disorders, including stroke, has challenged the non-regenerative capacity of the brain. Among the many treatment strategies tailored towards repairing the injured brain, stem cell-based therapeutics have been demonstrated as safe and effective in animal models of stroke, and are being tested in limited clinical trials. We address here key lab-to-clinic translational research that relate to efficacy, safety, and mechanism of action underlying st...

Evaluation of transcatheter arterial chemoembolization combined with radiofrequency capacitive heating on clinical therapeutic effect of metastatic carcinoma

International Nuclear Information System (INIS)

Chen Qianli; Ye Qiang; Gu Weizhong; Zhang Jiazhong; Tong Qiangang; Xi Shunfa

2006-01-01

Objective: To evaluate clinical therapeutic efficacy and adverse efficacy of transcatheter arterial chemoembolization (TACE) combined with radiofrequency capacitive heating (RCH) for metastatic hepatic carcinoma (MHC). Methods: Thirty-nine cases of MHC were enrolled in this study and divided into two groups: study group (n=19) and control group (n=20). Before therapy, the Karnofsky's score of the patients was all beyond 60. Results: The carcinoma growth rate of the study group was -(0.38±0.22), while that of the control group was -(0.13±0.25), showing significant statistical difference (P 0.05). Conclusion: The therapeutic effect of MHC can be further improved by the treatment of TACE combined with radiofrequency capacitive heating without increase of adverse side effects. (authors)

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

Science.gov (United States)

Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

2014-02-19

Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice

OpenAIRE

Judge, Adam D.; Robbins, Marjorie; Tavakoli, Iran; Levi, Jasna; Hu, Lina; Fronda, Anna; Ambegia, Ellen; McClintock, Kevin; MacLachlan, Ian

2009-01-01

siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in b...

Preexisting Antibodies to an F(ab′)2 Antibody Therapeutic and Novel Method for Immunogenicity Assessment

OpenAIRE

Ruppel, Jane; Brady, Ann; Elliott, Rebecca; Leddy, Cecilia; Palencia, Marco; Coleman, Daniel; Couch, Jessica A.; Wakshull, Eric

2016-01-01

Anti-therapeutic antibodies (ATAs) may impact drug exposure and activity and induce immune complex mediated toxicity; therefore the accurate measurement of ATA is important for the analysis of drug safety and efficacy. Preexisting ATAs to the hinge region of anti-Delta like ligand 4 (anti-DLL4) F(ab′)2, a potential antitumor therapeutic, were detected in cynomolgus monkey serum, which presented a challenge in developing assays for detecting treatment induced ATA. A total ATA assay was develop...

Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

H.A. Daniel Lagassé

2017-02-01

Full Text Available Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016.

Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

Directory of Open Access Journals (Sweden)

Bernard Waeber

2008-02-01

Full Text Available Bernard Waeber1, Jean-Jacques Mourad21Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland; 2Hôpital Avicienne, Bobigny, FranceAbstract: A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118, a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108, or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103. The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 ± 70.5 (mean ± SD using the fixed-dose combination strategy, compared with –7.2 ± 81.0 using the sequential monotherapy approach and –17.5 ± 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril and a diuretic (indapamide.Keywords: antihypertensive therapy, tolerability, antihypertensive efficacy, fixed-dose combination, sequential monotherapy, stepped-care treatment

A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

Directory of Open Access Journals (Sweden)

Lorf Thomas

2010-04-01

Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

Physical Therapists in Primary Care Are Interested in High Quality Evidence Regarding Efficacy of Therapeutic Ultrasound for Knee Osteoarthritis: A Provincial Survey

Directory of Open Access Journals (Sweden)

Norma J. MacIntyre

2013-01-01

Full Text Available Recent high-level evidence favours therapeutic ultrasound (US for reducing pain in people with knee osteoarthritis (OA. It is unknown how current practice patterns align with current evidence regarding US efficacy and whether physical therapists perceive a need for further high-level evidence. We conducted a descriptive electronic survey to characterize the beliefs and use of US among physical therapists in Ontario treating people with nonsurgical knee OA. Most of the 123 respondents (81% reported at least some use of US with 45% using it often or sometimes. The main goal for using US was to reduce pain in the surrounding soft tissue (n=66 and/or the knee joint (n=43. Almost half (46% endorsed the belief that US is likely to be beneficial for clients with nonsurgical knee OA. Most respondents (85% expressed interest in the results of a randomized controlled trial evaluating the effectiveness of US on pain and physical function. Patterns of use reflect the respondents’ belief that US is likely to be beneficial for knee OA pain.

Efficacy of various schemes of therapy of patients with radiation limb edema

International Nuclear Information System (INIS)

Kuz'mina, E.G.; Degtyareva, A.A.; Zubova, N.D.; Guseva, L.I.; Klimanov, M.E.

1987-01-01

The efficacy of various therapeutic schemes: medicinal (basic therapy - BT), acupuncture (AP) and laser therapy (LT) against a background of basic therapy - was assessed and compared in 36 patients with radiation limb edema. It was established that a degree of a decrease in edemas, the improvement of indices of rheovasography grew in the following order: BT → AP → LT. The recovery of the lymph flow and immunological indices were the same in all therapeutic schemes

In Vivo Efficacy and Pharmacokinetics of Optimized Apidaecin Analogs

Science.gov (United States)

Schmidt, Rico; Knappe, Daniel; Wende, Elisabeth; Ostorházi, Eszter; Hoffmann, Ralf

2017-03-01

Proline-rich antimicrobial peptides (PrAMPs) represent promising alternative therapeutic options for the treatment of multidrug-resistant bacterial infections. PrAMPs are predominantly active against Gram-negative bacteria by inhibiting protein expression via at least two different modes of action, i.e., blocking the ribosomal exit tunnel of 70S ribosomes (oncocin-type binding) or inhibiting the assembly of the 50S ribosomal subunit (apidaecin-type binding). The in vivo efficacy and favorable biodistribution of oncocins confirmed the therapeutic potential of short PrAMPs for the first time, whereas the in vivo evaluation of apidaecins is still limited despite the promising efficacy of apidaecin-analog Api88 in an intraperitoneal murine infection model. Here, the in vivo efficacy of apidaecin-analog Api137 was studied, which rescued all NMRI mice from a lethal intraperitoneal infection with E. coli ATCC 25922 when administered three times intraperitoneal at doses of 0.6 mg/kg starting one hour after infection. When Api88 and Api137 were administered intravenous or intraperitoneal at doses of 5 and 20 mg/kg, their plasma levels were similarly low (<3 µg/mL) and fourfold lower than for oncocin-analog Onc72. This contradicted earlier expectation based on the very low serum stability of Api88 with a half-life time of only 5 min compared to 6 hrs and 3 hrs for Api137 and Onc72, respectively. Pharmacokinetic data relying on a sensitive mass spectrometry method utilizing multiple reaction monitoring and isotope-labeled peptides revealed that Api88 and Api137 were present in blood, urine, and kidney, and liver homogenates at similar levels accompanied by the same major metabolites comprising residues 1-16 and 1-17. The pretended discrepancy was solved, when all peptides were incubated in peritoneal lavage. Api137 was rapidly degraded at the C-terminus, while Api88 was rather stable despite releasing the same degradation products. Onc72 was very stable explaining its higher

Improving lithium therapeutics by crystal engineering of novel ionic cocrystals.

Science.gov (United States)

Smith, Adam J; Kim, Seol-Hee; Duggirala, Naga K; Jin, Jingji; Wojtas, Lukasz; Ehrhart, Jared; Giunta, Brian; Tan, Jun; Zaworotko, Michael J; Shytle, R Douglas

2013-12-02

Current United States Food and Drug Administration (FDA)-approved lithium salts are plagued with a narrow therapeutic window. Recent attempts to find alternative drugs have identified new chemical entities, but lithium's polypharmacological mechanisms for treating neuropsychiatric disorders are highly debated and are not yet matched. Thus, re-engineering current lithium solid forms in order to optimize performance represents a low cost and low risk approach to the desired therapeutic outcome. In this contribution, we employed a crystal engineering strategy to synthesize the first ionic cocrystals (ICCs) of lithium salts with organic anions. We are unaware of any previous studies that have assessed the biological efficacy of any ICCs, and encouragingly we found that the new speciation did not negatively affect established bioactivities of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics compared to lithium carbonate. Indeed, the studies detailed herein represent an important advancement in a crystal engineering approach to a new generation of lithium therapeutics.

Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress.

Science.gov (United States)

Guo, Dawei; Zhang, Junren; Huang, Zhihai; Jiang, Shanxiang; Gu, Ning

2015-02-01

Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy. Copyright © 2015. Published by Elsevier B.V.

Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

Science.gov (United States)

Anusuya, Shanmugam; Natarajan, Jeyakumar

2012-12-01

Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

Clinical efficacy of paclitaxel in the treatment of mid-stage and ...

African Journals Online (AJOL)

Conclusion: Paclitaxel has a significant effect when used to treat mid-stage and advanced gastric cancer. Moreover, additional nursing not only enhances the therapeutic effect but also improves prognosis and quality-of-life. Keywords: Paclitaxel, Mid-stage/advanced cancer, Gastric cancer, Nursing efficacy, Karnofsky ...

The therapeutic relationship in e-therapy for mental health: a systematic review.

Science.gov (United States)

Sucala, Madalina; Schnur, Julie B; Constantino, Michael J; Miller, Sarah J; Brackman, Emily H; Montgomery, Guy H

2012-08-02

E-therapy is defined as a licensed mental health care professional providing mental health services via e-mail, video conferencing, virtual reality technology, chat technology, or any combination of these. The use of e-therapy has been rapidly expanding in the last two decades, with growing evidence suggesting that the provision of mental health services over the Internet is both clinically efficacious and cost effective. Yet there are still unanswered concerns about e-therapy, including whether it is possible to develop a successful therapeutic relationship over the Internet in the absence of nonverbal cues. Our objective in this study was to systematically review the therapeutic relationship in e-therapy. We searched PubMed, PsycINFO, and CINAHL through August 2011. Information on study methods and results was abstracted independently by the authors using a standardized form. From the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic relationship. The majority of the reviewed studies were focused on the therapeutic alliance-a central element of the therapeutic relationship. Although the results do not allow firm conclusions, they indicate that e-therapy seems to be at least equivalent to face-to-face therapy in terms of therapeutic alliance, and that there is a relationship between the therapeutic alliance and e-therapy outcome. Overall, the current literature on the role of therapeutic relationship in e-therapy is scant, and much more research is needed to understand the therapeutic relationship in online environments.

Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

Science.gov (United States)

Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A.

2016-01-01

Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection. PMID:27893810

Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

Directory of Open Access Journals (Sweden)

Olivia Perwitasari

Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

International Nuclear Information System (INIS)

Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

2006-01-01

Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm 3 . When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P 131 I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

Therapeutic Drug Monitoring in Rheumatic Diseases

Directory of Open Access Journals (Sweden)

NG Hoi-Yan Alexandra

2016-12-01

Full Text Available The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors.

A readily applicable strategy to convert peptides to peptoid-based therapeutics.

Directory of Open Access Journals (Sweden)

Minyoung Park

Full Text Available Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics.

Tiapride: Therapeutic possibilities of its use in narcology, gerontopsychiatry, and in the treatment of Tourette's syndrome

Directory of Open Access Journals (Sweden)

Aleksandr Nikolaevich Basov

2013-01-01

Full Text Available The literature review deals with the evaluation of the efficacy and safety of tiapride used in the treatment of addictions of alcohol and psychoactive substances, such as opiate and heroin, vascular dementia with the signs of acute psychic confusion and Tourette's syndrome. The spectrum of neurochemical activity and mechanism of action of tiapride and the possibility of its combination with other drugs to enhance the therapeutic efficacy in the above disorders are described.

Therapeutic affordances of social media: emergent themes from a global online survey of people with chronic pain.

Science.gov (United States)

Merolli, Mark; Gray, Kathleen; Martin-Sanchez, Fernando

2014-12-22

: "exploration" (52/155, 33.5% of quotes), "connection" (50/155, 32.3% of quotes), "narration" (33/155, 21.3% of quotes), "adaptation" (13/155, 8.4% of quotes), and "self-presentation" (7/155, 4.5% of quotes). Of the most described affordances, "exploration" was based on a propensity for participants to explain their social media use for information seeking purposes. "Connection" placed greater emphasis on interaction, highlighting themes of "exchanging information" and "mitigating isolation". Responses regarding "narration" highlighted the value of shared experiences and the emotionally cathartic role this plays. Much of the efficacy of social media may be explicable via a closer examination of therapeutic affordances. Particular areas that warrant attention include social media's ability to filter and guide people to useful information, connect individuals, and share experiences. Further research into a variety of chronic conditions is warranted. Coupled with the results of the present study, a greater theoretical basis detailing how social media may foster health outcomes may lead to an improved evidence base for conducting research and may inform recommendations for social media use in chronic disease management.

Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

Science.gov (United States)

Geszke-Moritz, Małgorzata; Moritz, Michał

2016-11-01

This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

Science.gov (United States)

Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

2017-08-01

Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

Comparison between anti-CEA and anti-HER2 212Pb-labeled mAbs during α-RIT of small volume peritoneal carcinomatosis - Role of activity distribution on therapeutic efficacy and toxicity?

International Nuclear Information System (INIS)

Elgqvist, J.; Boudousq, V.; Bobyk, L.; Busson, M.; Lozza, C.; Navarro-Teulon, I.; Pouget, J.P.; Maquaire, P.; Torgue, J.

2015-01-01

absorbed doses were shown to be higher for 212 Pb-35A7 mAb than for 212 Pb-Trastuzumab (35.5 Gy versus 27.6 Gy, respectively). Investigation of potential relationships between distribution of radioactivity at the tissue level and biological parameters is ongoing. Conclusions: we have investigated the therapeutic efficacy of 212 Pb-labeled mAbs in i.p. α-RIT of small tumors. A higher efficacy per decay, of internalizing versus non-internalizing 212 Pb-labeled mAbs was found. Investigations if a lack of absorbed dose/therapeutic efficacy relationship could be due to heterogeneity in the radioactivity distribution are ongoing. (authors)

Efficacy of teachers in a number of selected schools in the KwaZulu ...

African Journals Online (AJOL)

Erna Kinsey

Teacher efficacy is a type of self-efficacy — a cognitive process in which people ... inclined to refer a difficult student to special education. Teachers with ..... An even greater percentage of them (86%) took a huge work load home from time to.

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

Directory of Open Access Journals (Sweden)

Jan B W J Cornelissen

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

Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12.

Science.gov (United States)

Bozeman, Erica N; He, Sara; Shafizadeh, Yalda; Selvaraj, Periasamy

2016-01-01

Immunotherapeutic approaches have emerged as promising strategies to treat various cancers, including breast cancer. A single approach, however, is unlikely to effectively combat the complex, immune evasive strategies found within the tumor microenvironment, thus novel, effective combination treatments must be explored. In this study, we investigated the efficacy of a combination therapy consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs) B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12 completely inhibited tumor formation which was correlative with robust HER-2 specific CTL activity. However, in a therapeutic setting, both cellular vaccination and PD-L1 blockade induced only 10-20% tumor regression when administered alone but resulted in 50% tumor regression as a combination therapy. This protection was significantly hindered following CD4 or CD8 depletion indicating the essential role played by cellular immunity. Collectively, these pre-clinical studies provide a strong rationale for further investigation into the efficacy of combination therapy with tumor cell vaccines adjuvanted with membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast cancer.

Heroin refusal self-efficacy and preference for medication-assisted treatment after inpatient detoxification.

Science.gov (United States)

Kenney, Shannon R; Bailey, Genie L; Anderson, Bradley J; Stein, Michael D

2017-10-01

An individual's self-efficacy to refuse using heroin in high-risk situations is believed to minimize the likelihood for relapse. However, among individuals completing inpatient heroin detoxification, perceived refusal self-efficacy may also reduce one's perceived need for medication-assisted treatment (MAT), an effective and recommended treatment for opioid use disorder. In the current study, we examined the relationship between heroin refusal self-efficacy and preference for MAT following inpatient detoxification. Participants (N=397) were interviewed at the start of brief inpatient opioid detoxification. Multiple logistic regression was used to estimate the adjusted association of background characteristics, depressed mood, and perceived heroin refusal self-efficacy with preference for MAT. Controlling for other covariates, depressed mood and lower perceived refusal self-efficacy were associated with a significantly greater likelihood of expressing preference for MAT (versus no MAT). Perceived ability to refuse heroin after leaving detox is inversely associated with a heroin user's desire for MAT. An effective continuum of care model may benefit from greater attention to patient's perceived refusal self-efficacy during detoxification which may impact preference for MAT and long-term recovery. Copyright © 2017. Published by Elsevier Ltd.

Complete Biological Evaluation of Therapeutical Radiopharmaceuticals in Rodents, Laboratory Beagles and Veterinary Patients - Preclinical Distribution-, Kinetic-, Excretion-, Internal Dosimetry-, Radiotoxicological-, Radiation Safety- and Efficacy Data

International Nuclear Information System (INIS)

Balogh, L.; Domokos, M.; Polyak, A.; Thuroczy, J.; Janoki, G.

2009-01-01

The research and development of various novel therapeutical radiopharmaceuticals is a huge demand in many laboratories world-wide. Beside of multiple bone metastases pain-palliation and radiosynovectomy agents a number of specific radiopharmaceutical applicants mainly for oncological applications are in the pipeline. Numerous in vitro methods are available in the first line to test the radiolabelling efficiency, the possible radioactive and non-labelled impurities, the stability of the label at different conditions and mediums, and some specific characteristics of radiopharmaceutical applicants eg.: receptor binding assays, antigen-antibody assays. But, still before human clinical trials there are several questions to be solved in regards of toxicology, radiotoxicology, radiation safety and maybe most importantly the efficacy tasks. All these issues cannot be answered without animal tests. Several decades back animal tests in radiopharmacy meant only standard bioassays in a large number of healthy rodents. Later on pathological models eg.: human tumor xenografts in immunodeficient animals came-out and through them radiopharmaceutical tumor-uptake by the targets were available to evaluate in vivo as well. Xenografts are still popular and widely used models in the field but instead of wide-scaled bioassays nowadays repeated scintiscans or hybrid images (SPECT/CT, PET/CT) are more and more often used to answer kinetic-, excretion-, tumor uptake, internal dosimetry (Minimum Effective Dose, Maximum Tolerable Dose, critical organ doses, tumor doses) questions. Greater animals like laboratory Beagles are more closely in size, clinical and metabolic parameters to the human objects so playing a more perfect role of human medical doctor and especially veterinary patients. Easy to understand that many of the spontaneously occurring companion animal diseases are a good model of human pathological diseases. The need of a better diagnosis and treatment of that animals meets with

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

International Nuclear Information System (INIS)

Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

2012-01-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Energy Technology Data Exchange (ETDEWEB)

Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

2012-10-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Efficacy of oral iodized peanut oil is greater than that of iodized poppy seed oil among Indonesian schoolchildren

NARCIS (Netherlands)

Untoro, J.; Schultink, J.W.; West, C.E.; Gross, R.; Hautvast, J.G.A.J.

2006-01-01

Background: Oral iodized poppy seed oil is an appropriate measure for controlling iodine deficiency in areas where iodized salt is not yet available. However, a more effective and cheaper iodized oil preparation is needed. Objective: The aim of this study was to compare the efficacy of iodized

Annexin V Imaging Detects Diabetes-Accelerated Apoptosis and Monitors the Efficacy of Benfotiamine Treatment in Ischemic Limbs of Mice

Directory of Open Access Journals (Sweden)

Kyung-Ho Jung

2014-05-01

Full Text Available The role of apoptosis imaging for monitoring treatment response in ischemic limbs has not been properly explored. In this study, we investigated the ability of annexin V (AnxV imaging to assess the efficacy of antiapoptotic treatment in ischemic limbs of diabetic mice. Normal C57BL/6 mice and streptozotocin-induced diabetic mice were subject to hindlimb ischemia. AnxV-conjugated fluorescent streptavidin probes were intravenously injected, and optical imaging was performed. Tissue apoptosis was quantified by histochemistry and Western blotting. The AnxV probes showed specific targeting to apoptotic cells on confocal microscopy and flow cytometry. Intravenous AnxV probes displayed substantially greater accumulation in ischemic limbs of diabetic mice. Benfotiamine (BFT treatment of diabetic mice led to better perfusion recovery on laser Doppler imaging and reduced AnxV binding on optical imaging. TUNEL staining and cleaved caspase-3 Western blots confirmed accelerated apoptosis by diabetes and its suppression by BFT treatment. Furthermore, AnxV-SAv-PEcy5.5 uptake in the ischemic limbs closely correlated to cleaved caspase-3 expression. Thus, AnxV imaging may be useful for monitoring the efficacy of therapeutic agents designed to suppress ischemia-induced apoptosis.

Annexin V imaging detects diabetes-accelerated apoptosis and monitors the efficacy of benfotiamine treatment in ischemic limbs of mice.

Science.gov (United States)

Jung, Kyung-Ho; Lee, Jin Hee; Park, Jin Won; Paik, Jin Young; Quach, Cung Hoa Thien; Lee, Eun Jeong; Lee, Kyung-Han

2014-01-01

The role of apoptosis imaging for monitoring treatment response in ischemic limbs has not been properly explored. In this study, we investigated the ability of annexin V (AnxV) imaging to assess the efficacy of antiapoptotic treatment in ischemic limbs of diabetic mice. Normal C57BL/6 mice and streptozotocin-induced diabetic mice were subject to hindlimb ischemia. AnxV-conjugated fluorescent streptavidin probes were intravenously injected, and optical imaging was performed. Tissue apoptosis was quantified by histochemistry and Western blotting. The AnxV probes showed specific targeting to apoptotic cells on confocal microscopy and flow cytometry. Intravenous AnxV probes displayed substantially greater accumulation in ischemic limbs of diabetic mice. Benfotiamine (BFT) treatment of diabetic mice led to better perfusion recovery on laser Doppler imaging and reduced AnxV binding on optical imaging. TUNEL staining and cleaved caspase-3 Western blots confirmed accelerated apoptosis by diabetes and its suppression by BFT treatment. Furthermore, AnxV-SAv-PEcy5.5 uptake in the ischemic limbs closely correlated to cleaved caspase-3 expression. Thus, AnxV imaging may be useful for monitoring the efficacy of therapeutic agents designed to suppress ischemia-induced apoptosis.

The therapeutic alliance: a psychoanalytic perspective.

Science.gov (United States)

Freebury, D R

1989-11-01

Psychoanalysis has long distinguished between the transference neurosis and that part of the communication between therapist and patient which depends upon a relatively intact part of the patient's ego. It has been proposed that it is this capacity of the patient that sustains the difficult work of dealing with communications which are the consequence of transference, and which often threaten the viability of the treatment. This quality has been referred to variously as the unobjectionable positive transference, rational transference, mature transference, therapeutic alliance and working alliance. The ever broadening scope of Psychoanalysis, along with our greater knowledge of early childhood development, has enhanced our understanding of the many influences affecting the treatment alliances. Newer views of the transference, which stress the significance of the therapists' contributions to the therapeutic dyad, make it clear that the therapeutic alliance can no longer be explained as some simple, reality based, conflict free, motivating force. It involves, rather, a complex interaction of several factors, to each of which one must add the therapists' reciprocal reactions. Psychotherapy outcome research will need to take all of these factors into consideration.

Prospective utility of therapeutic ultrasound in dentistry-Review with recent comprehensive update

Directory of Open Access Journals (Sweden)

Shalu Rai

2012-01-01

Full Text Available Background: The utility of ultrasound (US for therapeutic purposes is still in its infancy. Therapeutic US (TUS has been used widely in medical field for urological application, surgical intervention, bone healing, and osteointegration in cancer and healing of full thickness excised skin lesions, and within dentistry as a prediagnostic, diagnostic and therapeutic purpose. The purpose of the paper is to review and determine the efficacy of US as one of the treatment modalities for its role in maxillofacial region to reduce pain and promote soft tissue healing. Materials and Methods: A Medline search included of the international literature published between 1976 and 2011 and was restricted to English language articles, published work of past researchers including in vitro and in vivo studies, recent additions of textbooks on surgical and therapeutic applications of US and, current articles in conference papers and reports accessed from the internet using Google search engine on therapeutic ultrasound. Results: Very few article regarding effect of therapeutic of US for its use of insonation for treatment of patient with pain and soft tissue injury are available. This review article mainly emphasizes the therapeutic utility of US in dentistry for its effectiveness to decrease joint stiffness, reduce pain and muscle spasms and improve muscle mobility. In vivo studies have shown very little clinical effects. Conclusions: Further research is warranted in this clinically important area to make the development of noninvasive, multifunctional ultrasound devices for repair, regeneration and other therapeutic utility a success.

Teaching efficacy of nurses in clinical practice education: A cross-sectional study.

Science.gov (United States)

Kim, Eun-Kyeung; Shin, Sujin

2017-07-01

Clinical nurses play a vital role in clinical practice education; thus, it is necessary to help clinical nurses have teaching efficacy through the development and application of systematic education programs. To identify nurses' teaching efficacy for clinical education and analyze the influencing factors of teaching efficacy. The study used a cross-sectional design. We used a convenience sample of 263 nurses from two hospitals. Teaching efficacy, general characteristics, and perception of clinical practice education were collected via self-reported questionnaires. Teaching efficacy was measured using Hwang's (2006) questionnaire, while perception of clinical practice education was measured using the Clinical Nurse Teacher Survey developed by Nishioka et al. (2014). Participants completed the questionnaire directly. The collected data were then analyzed using descriptive statistics, t-tests, ANOVAs, and multiple regression analysis with PASW Statistics 18.0. The mean total score of teaching efficacy was 72.5 (range 21-105). The leadership for students subscale had the highest score (3.56±0.59). The factors influencing teaching efficacy were length of clinical career (β=0.26, pteaching efficacy in nurses. Based on these results, nursing educators might need to develop greater confidence in their knowledge and enhance control of their teaching strategies. Nursing schools and hospitals might need to provide greater support and educational opportunities to nurse clinical practice instructors. Furthermore, constructing a system of cooperation between these colleges and educational hospitals, developing programs to enhance teaching efficacy, and identifying the clinical instructor's role are all necessary to promote clinical practice education. Copyright © 2017. Published by Elsevier Ltd.

Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin resistant mouse B16-BL6 melanoma.

Science.gov (United States)

Gautam, S C; Chikkala, N F; Lewis, I; Grabowski, D R; Finke, J H; Ganapathi, R

1992-01-01

Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM-resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM-resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype.

Therapeutic enhancement of newly derived bacteriocins against Giardia lamblia.

Science.gov (United States)

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. Copyright © 2014 Elsevier Inc. All rights reserved.

The relationship between adult attachment style and therapeutic alliance in individual psychotherapy: a meta-analytic review.

Science.gov (United States)

Diener, Marc J; Monroe, Joel M

2011-09-01

The present study examined the relationship between adult attachment style and therapeutic alliance in individual psychotherapy. Search procedures yielded 17 independent samples (total N = 886, average n = 52, standard deviation = 24) for inclusion in the meta-analysis. Results indicated that greater attachment security was associated with stronger therapeutic alliances, whereas greater attachment insecurity was associated with weaker therapeutic alliances, with an overall weighted effect size of r = .17, p .10) with the exception of the source of alliance ratings; results indicated that patient-rated alliance demonstrated a significantly larger relationship with attachment compared with therapist-rated alliance (Qbetween = 3.95, df = 1, p = .047). Implications for clinical practice and future research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved). (c) 2011 APA, all rights reserved.

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

Science.gov (United States)

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

2008-01-01

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

Evaluation of pulmonary hypertension and surgical therapeutic efficacy using first-pass radionuclide pulmonary perfusion imaging in patients with pulmonary hypertension of valvular heart disease

International Nuclear Information System (INIS)

Wang Xuemei; Shi Rongfang; Fang Wei; Wang Daoyu; Zhou Baogui; Wang Qi; Pan Shiwei

2004-01-01

Objective: To evaluate pulmonary hypertension (PH) and surgical therapeutic efficacy using first-pass radionuclide pulmonary perfusion imaging (FPPPI) and pulmonary perfusion imaging (PPI) in patients with PH of valvular heart disease. Methods: One hundred and sixteen patients with valvular disease were included in the study. Swan-Ganz catheterization, echocardiography, FPPPI and PPI were performed on all patients before surgery. The patients were divided into four groups. Results: 1) Correlation coefficients were 0.856, 0.503 and 0.572 (P<0.01) between lung equilibrium time (LET) by FPPPI, superior lung/low lung ratio (S/L) by PPI , systolic pulmonary arterial pressure (SPAP) from echocardiography and SPAP from the catheter manometer. 2)The sensitivity, specificity and accuracy of PAP using FPPPI measuring were 94.7%, 68.3% and 85.3%, respectively. The sensitivity, specificity and accuracy of PAP using PPI measuring were 78.8%, 52.8% and 70.7%, respectively. The sensitivity, specificity and accuracy of PAP using FPPPI plus PPI measuring were 96.4%, 72.7% and 89.7%, respectively. 3)LET by FPPPI before surgery and 5-14 d after surgery were (27.71 ± 10.85) and (20.96 ± 6.25) s, respectively (P<0.001). SPL by PPI were 1.43 ± 0.41 and 1.30 ± 0.35, respectively (P<0.001). 4) Complete improvement rates of LET in the PAP slightly risen group, moderately risen group and weightily risen group were 47.6%, 34.5% and 1/4, respectively; part improvement rates of LET for corresponding groups were 40.5%, 62.1% and 3/4, respectively (P<0.001). Complete improvement rates of SPL were 31.0%, 34.5% and 0/4, respectively; part improvement rates of SPL were 35.7%, 55.2% and 3/4, respectively (P<0.05). Complete improvement rates of LET + SPL were 57.1%, 58.6% and 1/4; part improvement rates of LET+SPL were 38.1%, 41.4% and 3/4, respectively (P<0.01). Conclusions: 1)FPPPI is better than PPI and echocardiography for evaluating PH in valvular heart disease. 2)Combined FPPPI and PPI can

Does Digital Game Interactivity Always Promote Self-Efficacy?

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Lee, Yu-Hao

2015-11-01

Interactive digital games can promote self-efficacy by engaging players in enactive and observational learning. However, interactivity does not always lead to greater self-efficacy. Important constructs in social cognitive theory, such as performance outcome and perceived similarity, are often not accounted for in studies that have tested the effect of digital game interactivity on self-efficacy. This study assessed the effects of interactive digital games compared with passive digital games based on video comparison, a common experimental design used to test the effect of digital game interactivity on self-efficacy. In addition, this study also evaluated player performance and measured perceived similarity to the observed player. Findings suggested that in general, digital game interactivity predicted higher self-efficacy compared with noninteractive passive games. However, in the noninteractive conditions, the effects of performance on self-efficacy were moderated by perceived similarity between the observer and the observed player. When the observed player was perceived to be similar to the observer, the effects of performance on self-efficacy were comparable to the interactive game, but when the observed player was perceived as dissimilar to the observer, observing the dissimilar player failed to increase observer self-efficacy. Implications for interactivity manipulations and game developers are discussed.

How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders.

Science.gov (United States)

Vandervert, Larry

2015-01-01

Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein's cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue that: (1) The foundational basis of the central executive begins in infancy as attentional control during the establishment of working memory, (2) In accordance with Akshoomoff, Courchesne and Townsend's and Leggio and Molinari's cerebellar sequence detection and prediction models, the rigors of volitional control demands of music training can enhance voluntary manipulation of information in thought and movement, (3) The music training-enhanced blending of cerebellar internal models in working memory as can be experienced as intuition in scientific discovery (as Einstein often indicated) or, equally, as moments of therapeutic advancement toward goals in the development of voluntary control in neurological disorders, and (4) The blending of internal models as in (3) thus provides a mechanism by which music training enhances central executive processes in working memory that can lead to scientific discovery and improved therapeutic outcomes in neurological disorders. Within the framework of Leggio and Molinari's cerebellar sequence detection model, it is determined that intuitive steps forward that occur in both scientific discovery and during therapy in those with neurological disorders operate according to the same mechanism of adaptive error-driven blending of cerebellar internal models. It is concluded that the entire framework of the central executive structure of working memory is a product of the cerebrocerebellar system which can, through the learning of internal models

[Pharmacokinetic alterations in pregnancy and use of therapeutic drug monitoring].

Science.gov (United States)

Panchaud, Alice; Weisskopf, Etienne; Winterfeld, Ursula; Baud, David; Guidi, Monia; Eap, Chin B; Csajka, Chantal; Widmer, Nicolas

2014-01-01

Following the thalidomide tragedy, pharmacological research in pregnant women focused primarily on drug safety for the unborn child and remains only limited regarding the efficacy and safety of treatment for the mother. Significant physiological changes during pregnancy may yet affect the pharmacokinetics of drugs and thus compromise its efficacy and/or safety. Therapeutic drug monitoring (TDM) would maximize the potential effectiveness of treatments, while minimizing the potential risk of toxicity for the mother and the fetus. At present, because of the lack of concentration-response relationship studies in pregnant women, TDM can rely only on individual assessment (based on an effective concentration before pregnancy) and remains reserved only to unexpected situations such as signs of toxicity or unexplained inefficiency. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Therapeutic exercises for the control of temporomandibular disorders

Directory of Open Access Journals (Sweden)

Alberto da Rocha Moraes

2013-10-01

Full Text Available INTRODUCTION: Temporomandibular disorder (TMD is a multifactorial disease. For this reason, it is difficult to obtain an accurate and correct diagnosis. In this context, conservative treatments, including therapeutic exercises classified as stretching, relaxation, coordination, strengthening and endurance, are oftentimes prescribed. OBJECTIVE: Thus, the aim of the present article was to conduct a literature review concerning the types of exercises available and the efficacy for the treatment of muscular TMD. METHODS: The review included researches carried out between 2000 and 2010, indexed on Web of Science, PubMed, LILACS and BBO. Moreover, the following keywords were used: Exercise, physical therapy, facial pain, myofascial pain syndrome, and temporomandibular joint dysfunction syndrome. Studies that did not consider the subject "TMD and exercises", used post-surgery exercises and did not use validated criteria for the diagnosis of TMD (RDC/TMD were not included. RESULTS: The results comprised seven articles which proved therapeutic exercises to be effective for the treatment of muscular TMD. However, these studies are seen as limited, since therapeutic exercises were not applied alone, but in association with other conservative procedures. In addition, they present some drawbacks such as: Small samples, lack of control group and no detailed exercise description which should have included intensity, repetition, frequency and duration. CONCLUSION: Although therapeutic exercises are considered effective in the management of muscular TMD, the development of randomized clinical trials is necessary, since many existing studies are still based on the clinical experience of professionals.

In Vitro Evaluation of Biofilm Dispersal as a Therapeutic Strategy To Restore Antimicrobial Efficacy

DEFF Research Database (Denmark)

Roizman, Dan; Vidaillac, Celine; Givskov, Michael

2017-01-01

As a proof-of-concept study, the direct impact of biofilm dispersal on the in vitro efficacy of imipenem and tobramycin was evaluated against 3-day-old biofilms of Pseudomonas aeruginosa. Arabinose induction of biofilm dispersal via activation of the phosphodiesterase YhjH in the P. aeruginosa en...

Comparison of Efficacy of Eye Movement, Desensitization and Reprocessing and Cognitive Behavioral Therapy Therapeutic Methods for Reducing Anxiety and Depression of Iranian Combatant Afflicted by Post Traumatic Stress Disorder

Science.gov (United States)

Narimani, M.; Sadeghieh Ahari, S.; Rajabi, S.

This research aims to determine efficacy of two therapeutic methods and compare them; Eye Movement, Desensitization and Reprocessing (EMDR) and Cognitive Behavioral Therapy (CBT) for reduction of anxiety and depression of Iranian combatant afflicted with Post traumatic Stress Disorder (PTSD) after imposed war. Statistical population of current study includes combatants afflicted with PTSD that were hospitalized in Isar Hospital of Ardabil province or were inhabited in Ardabil. These persons were selected through simple random sampling and were randomly located in three groups. The method was extended test method and study design was multi-group test-retest. Used tools include hospital anxiety and depression scale. This survey showed that exercise of EMDR and CBT has caused significant reduction of anxiety and depression.

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

Science.gov (United States)

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

2016-01-01

Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

Experience in treatment of hyperthyroidism with I-131 diagnosis, patient preparation and therapeutic procedure

International Nuclear Information System (INIS)

Zhongyun, Pan

2003-01-01

Treatment of hyperthyroidism with I-131 diagnosis is being performed after clinical diagnosis of thyrotoxicosis based on clinical manifestations of hypermetabolic state, serumT3 and T4 determination; medical preparation of patients and therapeutic procedure is obtained for better efficacy, relieve symptoms and prevent aggravation of thyrotoxicosis after I-131 treatment

Using PEGylated magnetic nanoparticles to describe the EPR effect in tumor for predicting therapeutic efficacy of micelle drugs.

Science.gov (United States)

Chen, Ling; Zang, Fengchao; Wu, Haoan; Li, Jianzhong; Xie, Jun; Ma, Ming; Gu, Ning; Zhang, Yu

2018-01-25

Micelle drugs based on a polymeric platform offer great advantages over liposomal drugs for tumor treatment. Although nearly all of the nanomedicines approved in the clinical use can passively target to the tumor tissues on the basis of an enhanced permeability and retention (EPR) effect, the nanodrugs have shown heterogenous responses in the patients. This phenomenon may be traced back to the EPR effect of tumor, which is extremely variable in the individuals from extensive studies. Nevertheless, there is a lack of experimental data describing the EPR effect and predicting its impact on therapeutic efficacy of nanoagents. Herein, we developed 32 nm magnetic iron oxide nanoparticles (MION) as a T 2 -weighted contrast agent to describe the EPR effect of each tumor by in vivo magnetic resonance imaging (MRI). The MION were synthesized by a thermal decomposition method and modified with DSPE-PEG2000 for biological applications. The PEGylated MION (Fe 3 O 4 @PEG) exhibited high r 2 of 571 mM -1 s -1 and saturation magnetization (M s ) of 94 emu g -1 Fe as well as long stability and favorable biocompatibility through the in vitro studies. The enhancement intensities of the tumor tissue from the MR images were quantitatively measured as TNR (Tumor/Normal tissue signal Ratio) values, which were correlated with the delay of tumor growth after intravenous administration of the PLA-PEG/PTX micelle drug. The results demonstrated that the group with the smallest TNR values (TNR EPR effect in patients for accurate medication guidance of micelle drugs in the future treatment of tumors.

Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis.

Science.gov (United States)

Suzuki, Hideo; Kaneko, Tsuyoshi; Mizokami, Yuji; Narasaka, Toshiaki; Endo, Shinji; Matsui, Hirofumi; Yanaka, Akinori; Hirayama, Aki; Hyodo, Ichinosuke

2013-05-07

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may become intractable when treated with conventional medications such as aminosalicylates, corticosteroids, and azathioprine. The herbal medicine Qing Dai has traditionally been used in Chinese medicine to treat UC patients, but there is a lack of published data on the efficacy of Qing Dai in UC treatment. We report several cases of patients with intractable UC who take Qing Dai in a retrospective observational study. Furthermore, we explore the mechanisms of action of Qing Dai. Nine patients with active UC who received conventional medications but wished to receive Qing Dai as an alternative medication were included in our analysis. The UC severity level was determined based on the clinical activity index (CAI). Additionally, 5 of the 9 patients were endoscopically evaluated according to the Matts grading system. Each patient received 2 g/d of Qing Dai orally and continued taking other medications for UC as prescribed. Electron spin resonance was applied to explore the mechanisms of action of Qing Dai. After 4 mo of treatment with Qing Dai, the CAI score decreased from 8.3 ± 2.4 to 2.4 ± 3.4 (mean ± SD; P Qing Dai possesses strong hydroxyl radical scavenging activity. Qing Dai showed significant clinical and endoscopic efficacy in patients who failed to respond to conventional medications. Scavenging of hydroxyl radicals appears to be a potential mechanism through which Qing Dai acts, but the significance of the scavenging ability of Qing Dai with respect to the anti-inflammatory effect in UC patients warrants further investigation.

Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

Science.gov (United States)

Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

2015-01-01

Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

Associations between depressive symptoms, self-efficacy, eating styles, exercise and body mass index in women.

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Clum, Gretchen A; Rice, Janet C; Broussard, Marsha; Johnson, Carolyn C; Webber, Larry S

2014-08-01

This article explores cross-sectional associations between depressive symptoms and body mass index (BMI) in women working in schools in the Greater New Orleans area. Self-efficacy for eating and exercise, eating styles, and exercise are examined as potential pathways. This is a secondary data analysis of 743 women who were participating in a workplace wellness randomized controlled trial to address environmental factors influencing eating and exercise behaviors using baseline data prior to the intervention. BMI was the primary outcome examined. Path analysis suggested that increased depressive symptoms were associated with increased BMI in women. Indirect effects of depressive symptoms on BMI were found for increased healthy eating self-efficacy, increased emotional eating, and decreased exercise self-efficacy. The association between greater healthy eating self efficacy and BMI was unexpected, and may indicate a suppressor effect of eating self-efficacy in the relationship between depressive symptoms and BMI in women. The findings suggest the importance of depressive symptoms to BMI in women. Targets for interventions to reduce BMI include targeting depressive symptoms and related sequelae including self-efficacy for exercise, and emotional eating. Further investigation of eating self-efficacy and BMI are recommended with particular attention to both efficacy for health eating and avoidance of unhealthy foods.

Radionuclides for therapeutic applications: Biological and medical aspects (present status, development and expectations)

International Nuclear Information System (INIS)

Wambersie, A.; Gahbauer, R.A.

2002-01-01

Different multidisciplinary therapeutic strategies and technical approaches are used today in cancer therapy. Among the techniques involving ionizing radiation, therapeutic applications of radioactive nuclides deserve a particular interest ; some clinical indications are well established, while several others are now being investigated, and some of them are promising. The efficacy of radionuclides in therapy often depends on technical factors such as specific activity, purity, chemical presentation, availability, etc. These factors are closely related, at least partly, to the production methods. This justifies the organization of the present Consultant's meeting by the IAEA. Brief information on cancer, its socio-economic aspects, and some data concerning cure rate are presented first

Efficacy of topical latanoprost versus minoxidil and betamethasone valerate on the treatment of alopecia areata.

Science.gov (United States)

El-Ashmawy, Amal Ahmad; El-Maadawy, Iman Hamed; El-Maghraby, Gamal Mohamed

2018-02-01

Alopecia areata (AA) is one of the most common causes of localized hair loss. There is no universally proven therapy that induces and sustains remission of hair growth in AA. To compare the efficacy and safety of topical latanoprost, minoxidil and betamethasone valerate on hair growth in patients with AA. Hundred patients with AA classified into five groups of 20 treated with: Group I, latanoprost 0.1% lotion; Group II, minoxidil 5% lotion; Group III, betamethasone valerate 0.1% solution; Group IV, combination of latanoprost lotion and betamethasone valerate solution and Group V, a vehicle lotion control group. There was a statistically significant improvement in all therapeutic groups when compared with control group and reduction of severity of alopecia tool score of scalp and beard before and after treatment for all therapeutic groups. Latanoprost, minoxidil and betamethasone valerate are effective and safe in the treatment of patchy AA. The use of latanoprost added to the therapeutic efficacy of topical betamethasone valerate in the treatment of AA and could be an effective adjunctive topical therapy for AA.

Gamma-Knife surgery (GKS) in patients with acromegaly: safety and efficacy

International Nuclear Information System (INIS)

Katz, D.; Miragaya, K.; Tenca, E.; Margni, A.; Artes, C.; Antico, J.

2007-01-01

The acromegaly is associated with increased morbidity and mortality than the general population. Since the surgical and pharmacological treatment for acromegaly have specific limitations, the GKS has been used as a therapeutic option in selected patients. The object is to evaluate the efficacy and safety of GKS in patients with acromegaly [es

[Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in a double-blind crossover experiment on chronic obstructive bronchopneumopathy].

Science.gov (United States)

Iaia, E

1990-01-01

The Authors describe a test performed on 20 hospitalized patients aged between 22 and 80, suffering from obstruent chronic broncho-pneumopathy. The test has been performed according to a double-blind pattern; each patient has been treated according to the 10-day long randomized scheme with one of the two drugs N-acetyl-L-cysteine, 4-carbomethoxythiazolidine. After a 7-day wash-out the patient has been treated with the other drug for a further period of 10 days. All patients have been administered both products at a dosage of 200 mg. three times a day. Every day following values have been registered: arterial pressure, body temperature; subjective and objective symptomatology relieves: cough, cephalea, asthenia, sibiluses, rhoncuses, rales, inspiratory and expiratory dyspnea. Furthermore before and after the treatment the quantity and the quality of the expectorate in order is evaluate the biologic tolerance of the examined drugs, before and after each treatment the following haematochemical and urinary tests have been performed: VES, azotemia, glycemia, SGOT, SGPT, LDH, alkaline phospatase, total and direct bilirubinaemia, prothrombinic activity, complete chemical analysis of urines. As shown in Tab. I-IX, a global analysis of the results proves that 4-carbomethoxythiazolidine is a very well-tolerated drug without any negative side-effect. As far as its therapeutic efficacy is concerned we can say that the mucolitic activity of 4-carbomethoxythiazolidine is the some of that of N-acetyl-L-cysteine.

Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential

OpenAIRE

Vij, Neeraj

2011-01-01

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions is airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hyper secretion in these diseases, that is further induc...

Pharmacokinetics, pharmacodynamics and clinical efficacy of omalizumab for the treatment of asthma.

Science.gov (United States)

Luu, Maxime; Bardou, Marc; Bonniaud, Philippe; Goirand, Françoise

2016-12-01

Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered: This drug evaluation summarizes published data on pharmacokinetic and pharmacodynamic properties of omalizumab, on clinical efficacy and safety, including real-world evidence, and provides a medico-economic evaluation of the drug. Expert opinion: Omalizumab represents an efficient therapeutic option for the management of patients with uncontrolled moderate/severe allergic asthma. It provides a significant reduction in the asthma exacerbation rate with a steroid-sparing effect, an improvement in quality of life in adults and adolescents, despite a lack of evidence about its efficacy specifically in severe allergic asthma. Clinical trials have demonstrated its efficacy in the pediatric population but further real-life evidence is expected to better characterize long-term effects in this population. There is still some debate about the optimal treatment duration but, to date, it is recommended not to stop the treatment as cessation has resulted in symptom recurrence. Omalizumab is an expensive treatment, but a key therapeutic option when used for uncontrolled severe allergic asthma.

The closer 'We' are, the stronger 'I' am: the impact of couple identity on cancer coping self-efficacy.

Science.gov (United States)

Ahmad, Saunia; Fergus, Karen; Shatokhina, Kristina; Gardner, Sandra

2017-06-01

The present study tested the supposition that greater levels of couple identity (or we-ness) increase a woman's coping self-efficacy in relation to breast cancer, which, in turn, predicts better psychosocial adjustment. Women (N = 112) in committed relationships completed surveys assessing their levels of couple identity, cancer coping self-efficacy, and aspects of their psychosocial adjustment (specifically, depression, anxiety and functional well-being) during one of their outpatient visits to the cancer centre. As predicted, the more women identified with their relationships, the lower their levels of depression and anxiety were and the greater their functional well-being was. This relationship was mediated by coping self-efficacy: greater identification with one's relationship predicted greater confidence in one's ability to cope, which, in turn, predicted better adjustment. The role intimate relationships play in women's adjustment to breast cancer, as well as directions for further research, are discussed.

The Role of Self-Esteem and Self-Efficacy in Detecting Responses to Feedback

Science.gov (United States)

1998-07-01

self -efficacy on a novel task may be a function of self - esteem and initial instruction on the task. It may be that low SEs initial self ...than will persons low in self -efficacy. This may also have implications for the interaction between self -efficacy and self - esteem . In situations...feedback than persons with low SE. Persons with low self - esteem are likely to perceive 32 greater feedback seeking costs (as noted earlier).

Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

International Nuclear Information System (INIS)

Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

2007-01-01

years. New potential therapeutic agents for OPI poisoning include: glycopyrrolate as anticholinergic; organophosphorous hydrolases, butyrilcholinesterases and sodium bicarbonate which degrade OPI and accelerate AChE reactivation; reversible anticholinesterases for reduction of AChE reinchibition; NMDA antagonist as neuroprotectors. Authors from Maryland have proposed the usage of IL-1 Rp antagonists in acute OPI intoxication, a new, original approach to therapy which deserves to be elucidated. For now pharmaceutical industries do not show satisfying initiative in developing new therapeutic agents and antidotes for OPI poisoning. However, randomized, controlled clinical studies, for the beginning with the agents which are in clinical practice, would elucidate their clinical efficacy, reduce the number of lethal pesticide poisonings in developing countries and provide information of special importance for the army and medical service. (author)

Therapeutic Efficacy of Endometrial Scratching in Repeated Controlled Ovarian Stimulation (COS) Failure Cycles

Science.gov (United States)

Wadhwa, Leena; Mishra, Mona

2018-01-01

Objective: The objective of the study was (1) “to evaluate the therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles.” And (2) “to compare differences in pregnancy outcome by endometrial scratching in early (D2–D4) and late follicular phases (D7–D9) of the same stimulation cycle.” Materials and Methods: Women attending infertility clinic in a tertiary care center and who have two or more repeated COS failure cycles and planned for COS with intrauterine insemination (IUI) were included in the study which is a prospective parallel, interventional, single-blinded, randomized control study, in 1:1 allocation ratio. A total of 165 patients were recruited and randomly allocated into three groups: Group A (n = 55) underwent endometrial scratching on D2–D4 of the same COS cycle, Group B (n = 55) on D7–D9, and Group C (n = 55) no intervention done. All the patients underwent COS according to standard protocol followed by IUI. Results: Clinical pregnancy rate was 12.73% (odds ratio [OR] =0.87 95% confidence interval [CI] =0.288–2.55, P = 1), 16.36% (OR = 1.15; 95% CI = 0.40–3.23, P = 1), and 14.54%, respectively, in Group A, B, and C, respectively (P = 0.86), as per intention to treat analysis. Using Chi-square test, P value between Group A and B was 0.787, between Group A and C was 1.000, and between Group B and C was 1.000. As per protocol analysis, clinical pregnancy rate was 13.46% (OR = 0.83; 95% CI = 0.27–2.5, P = 0.74), 19.57% (OR = 1.3 95%; CI = 0.45–3.73, P = 0.41), and 15.69%. Using Chi-square test, Pvalue between Group A and B was 0.588, between Group A and C was 0.967, and between Group B and C was 0.815. No abortions and multiple pregnancies occurred in either of the groups. Conclusion: The effect found was of good quantum in Group B as per protocol analysis which could be of clinical relevance if larger sample size would have been taken. Endometrial scratching is a cost

Therapeutic use of cannabis: Prevalence and characteristics among adults in Ontario, Canada.

Science.gov (United States)

Hamilton, Hayley A; Brands, Bruna; Ialomiteanu, Anca R; Mann, Robert E

2017-09-14

To investigate the prevalence of therapeutic cannabis use within a general population sample of adults and to describe various characteristics associated with use. Data were derived from the 2013 and 2014 CAMH Monitor Survey of adults in Ontario, Canada. This repeated cross-sectional survey employed a regionally stratified design and utilized computer-assisted telephone interviewing. Analyses were based on 401 respondents who reported using cannabis. The data indicated that 28.8% of those who used cannabis in the past year self-reported using cannabis for therapeutic purposes. Of therapeutic users, 15.2% reported having medical approval to use cannabis for therapeutic purposes. Cannabis use for therapeutic purposes was associated with more frequent use of cannabis, a moderate to high risk of problematic cannabis use, and a greater likelihood of using prescription opioids for medical purposes. There was little difference in cannabis use for therapeutic purposes according to sex, age, and marital status after adjusting for opioid use and problematic cannabis use. Findings suggest some potential negative consequences of cannabis use for therapeutic purposes; however, further research is needed to better understand the range and patterns of use and their corresponding vulnerabilities.

The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics.

Science.gov (United States)

Fishburn, C Simone

2008-10-01

Conjugation of macromolecules to polyethylene glycol (PEG) has emerged recently as an effective strategy to alter the pharmacokinetic (PK) profiles of a variety of drugs, and thereby to improve their therapeutic potential. PEG conjugation increases retention of drugs in the circulation by protecting against enzymatic digestion, slowing filtration by the kidneys and reducing the generation of neutralizing antibodies. Often, PEGylation leads to a loss in binding affinity due to steric interference with the drug-target binding interaction. This loss in potency is offset by the longer circulating half-life of the drugs, and the resulting change in PK-PD profile has led in some cases to enabling of drugs that otherwise could not be developed, and in others to improvements in existing drugs. Thus, whereas most approaches to drug development seek to increase the activity of drugs directly, the creation of PEGylated drugs seeks to balance the pharmacodynamic (PD) and pharmacokinetic properties to produce novel therapies that will meet with both increased efficacy and greater compliance in the clinical setting. This review examines some of the PEGylated drugs developed in recent years, and highlights some of the different strategies taken to employ PEG to maximize the overall PK-PD profiles of these compounds. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Girls' self-efficacy in the context of neighborhood gender stratification.

Science.gov (United States)

Soller, Brian; Jackson, Aubrey L

2018-05-01

Scholars have linked neighborhood characteristics to self-efficacy, but few have considered how gender factors into this association. We integrate literature on neighborhoods, gender stratification, and self-efficacy to examine the association between women's relative resources among neighborhood residents and adolescents' self-efficacy. We hypothesize that girls report more self-efficacy when they reside in neighborhoods where women have more socioeconomic resources relative to men. We test this hypothesis using data from the Project on Human Development in Chicago Neighborhoods and the 1990 Census. Results from multilevel regression models with gender-interacted effects indicate the neighborhood level of women's relative resources was not associated with boys' self-efficacy. However, girls reported higher self-efficacy when women's relative resources in their neighborhoods were greater. This association persisted after including potential individual- and neighborhood-level confounding variables. Our study underscores the importance of attending to gendered processes when understanding how neighborhoods impact youth. Copyright © 2018. Published by Elsevier Inc.

Do students with higher self-efficacy exhibit greater and more diverse scientific inquiry skills: An exploratory investigation in "River City", a multi-user virtual environment

Science.gov (United States)

Ketelhut, Diane Jass

In this thesis, I conduct an exploratory study to investigate the relationship between students' self-efficacy on entry into authentic scientific activity and the scientific inquiry behaviors they employ while engaged in that process, over time. Scientific inquiry has been a major standard in most science education policy doctrines for the past two decades and is exemplified by activities such as making observations, formulating hypotheses, gathering and analyzing data, and forming conclusions from that data. The self-efficacy literature, however, indicates that self-efficacy levels affect perseverance and engagement. This study investigated the relationship between these two constructs. The study is conducted in a novel setting, using an innovative science curriculum delivered through an interactive computer technology that recorded each student's conversations, movements, and activities while behaving as a practicing scientist in a "virtual world" called River City. River City is a Multi-User Virtual Environment designed to engage students in a collaborative scientific inquiry-based learning experience. As a result, I was able to follow students' moment-by-moment choices of behavior while they were behaving as scientists. I collected data on students' total scientific inquiry behaviors over three visits to River City, as well as the number of sources from which they gathered their scientific data. I analyzed my longitudinal data on the 96 seventh-graders using individual growth modeling. I found that self-efficacy played a role in the number of data-gathering behaviors students engaged in initially, with high self-efficacy students engaging in more data gathering than students with low self-efficacy. However, the impact of student self-efficacy on rate of change in data gathering behavior differed by gender; by the end of the study, student self-efficacy did not impact data gathering. In addition, students' level of self-efficacy did not affect how many different

Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women.

Science.gov (United States)

Ma, Linlin; Lin, Shouqing; Chen, Rong; Zhang, Ying; Chen, Fengling; Wang, Xiuli

2010-04-01

To assess therapeutic effect of an extract of Vitex agnus castus (VAC, BNO 1095) in premenstrual syndrome (PMS) in Chinese women. It was a prospective, randomised, double-blind, placebo-controlled study carried out in China. Eligible patients were treated with VAC extract or placebo for three cycles. Symptoms were documented with PMS diary (PMSD), a daily rating scale with 17 items. Main efficacy variable was the reduction percentage of 17 symptom score documented in PMSD during the luteal phase of the third treatment cycle. A total of 67 patients were enrolled and randomly assigned to VAC group or placebo group. Of these, 64 patients completed the study (31 vs. 33). All the 17 symptoms showed a significantly greater improvement with VAC than placebo (P 0.05). Vitex agnus castus is more effective than placebo in the treatment of moderate-to-severe PMS in Chinese women, especially in symptoms of negative effect and insomnia.

Efficacy of REACH Forgiveness across cultures.

Science.gov (United States)

Lin, Yin; Worthington, Everett L; Griffin, Brandon J; Greer, Chelsea L; Opare-Henaku, Annabella; Lavelock, Caroline R; Hook, Joshua N; Ho, Man Yee; Muller, Holly

2014-09-01

This study investigates the efficacy of the 6-hour REACH Forgiveness intervention among culturally diverse undergraduates. Female undergraduates (N = 102) and foreign extraction (46.2%) and domestic (43.8%) students in the United States were randomly assigned to immediate treatment or waitlist conditions. Treatment efficacy and the effect of culture on treatment response were assessed using measures of emotional and decisional forgiveness across 3 time periods. Students in the treatment condition reported greater improvement in emotional forgiveness, but not decisional forgiveness, relative to those in the waitlist condition. Gains were maintained at a 1-week follow-up. Although culture did not moderate the effect of treatment, a main effect of culture on emotional forgiveness and marginally significant interaction effect of culture on decisional forgiveness were found. The REACH Forgiveness intervention was efficacious for college students from different cultural backgrounds when conducted in the United States. However, some evidence may warrant development of culturally adapted forgiveness interventions. © 2014 Wiley Periodicals, Inc.

The anti-tumor efficacy of nanoparticulate form of ICD-85 versus free form

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Zare Mirakabadi, A.

2015-04-01

Full Text Available Biodegradable polymeric nanoparticles (NPs have been intensively studied as a possible way to enhance anti-tumor efficacy while reducing side effects. ICD-85, derived from the venom of two separate species of venomous animals, has been shown to exhibit anti-cancer activity. In this report polymer based sodium alginate nanoparticles of ICD-85 was used to enhance its therapeutic effects and reduce its side effects. The inhibitory effect was evaluated by MTT assay. The necrotic effect was assessed using LDH assay. The induction of apoptosis was analyzed by caspase-8 colorimetric assay kit. Cytotoxicity assay in HeLa cells demonstrated enhanced efficacy of ICD-85 loaded NPs compared to the free ICD-85. The IC50 values obtained in HeLa cells after 48 h, for free ICD-85 and ICD-85 loaded NPs were 26±2.9μg ml-1 and 18±2.5μg ml-1, respectively. While it was observed that free ICD-85 exhibits mild cytotoxicity towards normal MRC-5 cells (IC50>60μg ml-1, ICD-85 loaded NPs was found to have higher efficacy in anti-proliferative activity on HeLa cells in vitro without any significant cytotoxic effect on normal MRC-5 cells. The apoptosis-induction mechanism by both form of ICD-85 on HeLa cells was found to be through activation of caspase-8 with approximately 2 fold greater of ICD-85 loaded NPs as compared to free ICD-85. Our work reveals that although ICD-85 in free form is relatively selective to inhibit the growth of cancer cells via apoptosis as compared to normal cells, but nanoparticulate form increases its selectivity towards cancer cells.

Assessment of treatment efficacy and sebosuppressive effect of fractional radiofrequency microneedle on acne vulgaris.

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Lee, Kyung Real; Lee, Eo Gin; Lee, Hee Jung; Yoon, Moon Soo

2013-12-01

A minimally invasive fractional radiofrequency microneedle (FRM) device has been used in skin rejuvenation and acne scars, and a recent pilot study demonstrated the positive therapeutic effect on acne. We evaluated the efficacy of FRM device for acne vulgaris in Asians and conducted objective measurement to assess its effect on sebum production. Twenty Korean patients with acne vulgaris received a single full-face FRM treatment. Outcome assessments included standardized photography, physician's global assessment, patient's satisfaction scores, acne lesion count, and objective measurements of casual sebum level (CSL) and sebum excretion rate (SER). They were evaluated at baseline and 2, 4, 8 weeks after the treatment. After a single FRM treatment, the CSL and the SER showed 30-60% and 70-80% reduction, respectively, at week 2 (P acne severity and acne lesion count also revealed clinical improvement with maximum efficacy at week 2, but returned to the baseline in most patients by week 8. Patients' satisfaction scores (0-4) were above 2 on average, and adverse effects were minimal. This prospective study demonstrated the sebosuppressive effect from a single FRM treatment, but its therapeutic efficacy in acne requires further evaluation. © 2013 Wiley Periodicals, Inc.

Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

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Youcef M. Rustum

2010-01-01

Full Text Available Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.

Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

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Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

2015-01-01

Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

Colorectal cancer: diagnostic and therapeutic strategies

International Nuclear Information System (INIS)

Vaillant, J.C.

1996-01-01

Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)

Therapeutic Affordances of Social Media: Emergent Themes From a Global Online Survey of People With Chronic Pain

Science.gov (United States)

Gray, Kathleen; Martin-Sanchez, Fernando

2014-01-01

and renaming of therapeutic affordances: "exploration" (52/155, 33.5% of quotes), "connection" (50/155, 32.3% of quotes), "narration" (33/155, 21.3% of quotes), "adaptation" (13/155, 8.4% of quotes), and "self-presentation" (7/155, 4.5% of quotes). Of the most described affordances, "exploration" was based on a propensity for participants to explain their social media use for information seeking purposes. "Connection" placed greater emphasis on interaction, highlighting themes of "exchanging information" and "mitigating isolation". Responses regarding "narration" highlighted the value of shared experiences and the emotionally cathartic role this plays. Conclusions Much of the efficacy of social media may be explicable via a closer examination of therapeutic affordances. Particular areas that warrant attention include social media’s ability to filter and guide people to useful information, connect individuals, and share experiences. Further research into a variety of chronic conditions is warranted. Coupled with the results of the present study, a greater theoretical basis detailing how social media may foster health outcomes may lead to an improved evidence base for conducting research and may inform recommendations for social media use in chronic disease management. PMID:25533453

A comparison of efficacy of photoradiation therapy and other conventional treatment modalities on experimental MS-2 sarcoma

International Nuclear Information System (INIS)

Pazzoni, Gabriella; Savi, Giuseppina; Melloni, Elsa; Marchesini, Renato; Fava, Giannino; Locati, Lucia; Zunino, Franco

1984-01-01

The therapeutic efficacy of photoradiation therapy (PRT) following hematoporthyrin derivative (HpD) administration was compared in the experimental MS-2 tumour model to that of conventional treatment methods for local control of neoplastic diseases (i.e. surgery and radiotherapy). The therapeutic effects of PRT and surgical removal of primary tumour were comparable in these experiments. However, optimal effects were critically dependent on the stage of tumour development. In addition, the therapeutic advantage of PRT over radiotherapy suggests an interesting role of a new approach in tumours resistant to this conventional treatment. (author)

Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression.

Science.gov (United States)

Roseman, Leor; Nutt, David J; Carhart-Harris, Robin L

2017-01-01

< 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.

Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

Directory of Open Access Journals (Sweden)

Leor Roseman

2018-01-01

ASC (p < 0.05.Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797

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

Science.gov (United States)

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

2015-11-01

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

Graphene-based platforms for cancer therapeutics

Science.gov (United States)

Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

2016-01-01

Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management. PMID:26769305

Examining Technology and Teaching Efficacy of Preservice Teacher Candidates: A Deliberate Course Design Model

Science.gov (United States)

Willis, Jana M.

2015-01-01

Training programs that improve technology self-efficacy of teacher candidates will better prepare candidates to overcome technology challenges with greater levels of confidence. The purpose of this study was to examine self-efficacy levels of preservice teacher candidates who participated in scaffolded technology training designed to establish and…

Production and evaluation of Lutetium-177 maltolate as a possible therapeutic agent

International Nuclear Information System (INIS)

Hakimi, A.; Jalilian, A. R.; Bahrami Samani, A.; Ghannadi Maragheh, M.

2012-01-01

Development of oral therapeutic radiopharmaceuticals is a new concept in radiopharmacy. Due to the interesting therapeutic properties of 177 Lu and oral bioavailability of maltolate (MAL) metal complexes, 177 Lu-maltolate ( 177 Lu-MAL) was developed as a possible therapeutic compound for ultimate oral administration. The specific activity of 2.6-3 GBq/mg was obtained by irradiation of natural Lu 2 O 3 sample with thermal neutron flux of 4x10 13 n.cm -2 .s -1 for Lu-177. The product was converted into chloride form which was further used for labeling maltol (MAL). At optimized conditions a radiochemical purity of about >99% was obtained for 177 Lu-MAL shown by ITLC (specific activity, 970-1000 Mbq/mmole). The stability of the labeled compound as well as the partition coefficient was determined in the final solution up to 24h. Biodistribution studies of Lu-177 chloride and 177 Lu-MAL were carried out in wild-type rats for post-oral distribution phase data. Lu-MAL is a possible therapeutic agent in human malignancies for the bone palliation therapy so the efficacy of the compound should be tested in various animal models.

Internet-based treatment for PTSD reduces distress and facilitates the development of a strong therapeutic alliance: a randomized controlled clinical trial

Directory of Open Access Journals (Sweden)

Maercker Andreas

2007-04-01

Full Text Available Abstract Background The present study was designed to evaluate the efficacy of an internet-based therapy (Interapy for Posttraumatic Stress Disorder (PTSD in a German speaking population. Also, the quality of the online therapeutic relationship, its development and its relevance as potential moderator of the treatment effects was investigated. Method Ninety-six patients with posttraumatic stress reactions were allocated at random to ten sessions of Internet-based cognitive behavioural therapy (CBT conducted over a 5-week period or a waiting list control group. Severity of PTSD was the primary outcome. Secondary outcome variables were depression, anxiety, dissociation and physical health. Follow-up assessments were conducted at the end of treatment and 3 months after treatment. Results From baseline to post-treatment assessment, PTSD severity and other psychopathological symptoms were significantly improved for the treatment group (intent-to-treat group × time interaction effect size d = 1.40. Additionally, patients of the treatment condition showed significantly greater reduction of co-morbid depression and anxiety as compared to the waiting list condition. These effects were sustained during the 3-months follow-up period. High ratings of the therapeutic alliance and low drop-out rates indicated that a positive and stable therapeutic relationship could be established online. Significant improvement of the online working alliance in the course of treatment and a substantial correlation between the quality of the online relationship at the end of treatment and treatment outcome emerged. Conclusion Interapy proved to be a viable treatment alternative for PTSD with large effect sizes and sustained treatment effects. A stable and positive online therapeutic relationship can be established through the Internet which improved during the treatment process. Trial registration Australian Clinical Trials Registry ACTRN012606000401550

Ayahuasca's entwined efficacy: An ethnographic study of ritual healing from 'addiction'.

Science.gov (United States)

Talin, Piera; Sanabria, Emilia

2017-06-01

A range of studies has demonstrated the efficacy of the psychoactive Amazonian brew ayahuasca in addressing substance addiction. These have revealed that physiological and psychological mechanisms are deeply enmeshed. This article focuses on how interactive ritual contexts support the healing effort. The study of psychedelic-assisted treatments for addiction has much to gain from ethnographic analyses of healing experiences within the particular ecologies of use and care, where these interventions are rendered efficacious. This is an ethnographically grounded, qualitative analysis of addiction-recovery experiences within ayahuasca rituals. It draws on long-term fieldwork and participant observation in ayahuasca communities, and in-depth, semi-structured interviews of participants with histories of substance misuse. Ayahuasca's efficacy in the treatment of addiction blends somatic, symbolic and collective dimensions. The layering of these effects, and the direction given to them through ritual, circumscribes the experience and provides tools to render it meaningful. Prevailing modes of evaluation are ill suited to account for the particular material and semiotic efficacy of complex interventions such as ayahuasca healing for addiction. The article argues that practices of care characteristic of the ritual spaces in which ayahuasca is collectively consumed, play a key therapeutic role. The ritual use of ayahuasca stands in strong contrast to hegemonic understandings of addiction, paving new ground between the overstated difference between community and pharmacological interventions. The article concludes that fluid, adaptable forms of caregiving play a key role in the success of addiction recovery and that feeling part of a community has an important therapeutic potential. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.

Science.gov (United States)

Hegazy, Ahmed M; Yamada, Daisuke; Kobayashi, Masahiko; Kohno, Susumu; Ueno, Masaya; Ali, Mohamed A E; Ohta, Kumiko; Tadokoro, Yuko; Ino, Yasushi; Todo, Tomoki; Soga, Tomoyoshi; Takahashi, Chiaki; Hirao, Atsushi

2016-10-07

Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production. Inhibition of mitochondrial ATP synthetase was more effective in repressing sphere formation by Tsc1-deficient glioma cells than that by Tsc1-competent glioma cells, indicating a crucial function for mitochondrial bioenergetic capacity in GIC expansion. To translate this observation into the development of novel therapeutics targeting malignant gliomas, we screened drug libraries for small molecule compounds showing greater efficacy in inhibiting the proliferation/survival of Tsc1-deficient cells compared with controls. We identified several compounds able to preferentially inhibit mitochondrial activity, dramatically reducing ATP levels and blocking glioma sphere formation. In human patient-derived glioma cells, nigericin, which reportedly suppresses cancer stem cell properties, induced AMPK phosphorylation that was associated with mTORC1 inactivation and induction of autophagy and led to a marked decrease in sphere formation with loss of GIC marker expression. Furthermore, malignant characteristics of human glioma cells were markedly suppressed by nigericin treatment in vivo Thus, targeting mTORC1-driven processes, particularly those involved in maintaining a cancer cell's energy balance, may be an effective therapeutic strategy for glioma patients. © 2016 by The American

[Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of cefetamet pivoxil].

Science.gov (United States)

Nishimura, M; Kumamoto, Y; Hirose, T; Hayashi, K; Tsukamoto, T; Gohro, T; Ikegaki, S; Kamito, H; Inoke, T; Henmi, I

1990-07-01

We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1,000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).

Network Meta-Analysis Comparing the Efficacy of Therapeutic Treatments for Bronchiolitis in Children.

Science.gov (United States)

Guo, Caili; Sun, Xiaomin; Wang, Xiaowen; Guo, Qing; Chen, Dan

2018-01-01

This study aims to compare placebo (PBO) and 7 therapeutic regimens-namely, bronchodilator agents (BAs), hypertonic saline (HS), BA ± HS, corticosteroids (CS), epinephrine (EP), EP ± CS, and EP ± HS-to determine the optimal bronchiolitis treatment. We plotted networks using the curative outcome of several studies and specified the relations among the experiments by using mean difference, standardized mean difference, and corresponding 95% credible interval. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each therapy on clinical severity score (CSS) and length of hospital stay (LHS). This network meta-analysis included 40 articles from 1995 to 2016 concerning the treatment of bronchiolitis in children. All 7 therapeutic regimens displayed no significant difference to PBO with regard to CSS in our study. Among the 7 therapies, BA performed better than CS. As for LHS, EP and EP ± HS had an advantage over PBO. Moreover, EP and EP ± HS were also more efficient than BA. The SUCRA results showed that EP ± CS is most effective, and EP ± HS is second most effective with regard to CSS. With regard to LHS, EP ± HS ranked first, EP ± CS ranked second, and EP ranked third. We recommend EP ± CS and EP ± HS as the first choice for bronchiolitis treatment in children because of their outstanding performance with regard to CSS and LHS. © 2017 American Society for Parenteral and Enteral Nutrition.

Preempting Performance Challenges: The Effects of Inoculation Messaging on Attacks to Task Self-Efficacy

Science.gov (United States)

Jackson, Ben; Compton, Josh; Whiddett, Ryan; Anthony, David R.; Dimmock, James A.

2015-01-01

Although inoculation messages have been shown to be effective for inducing resistance to counter-attitudinal attacks, researchers have devoted relatively little attention toward studying the way in which inoculation theory principles might support challenges to psychological phenomena other than attitudes (e.g., self-efficacy). Prior to completing a physical (i.e., balance) task, undergraduates (N = 127, Mage = 19.20, SD = 2.16) were randomly assigned to receive either a control or inoculation message, and reported their confidence in their ability regarding the upcoming task. During the task, a confederate provided standardized negative feedback to all participants regarding their performance, and following the completion of the task, participants again reported their self-efficacy along with measures assessing in-task processes. Findings supported the viability of efficacy inoculation; controlling for pre-task self-efficacy, task performance, and relevant psycho-social variables (e.g., resilience, self-confidence robustness), participants in the inoculation condition reported greater confidence in their ability (i.e., task self-efficacy) than those in the control condition at post-task. Relative to those in the inoculation condition, participants in the control condition also experienced greater concentration disruption and self-presentation concerns during the task. PMID:25898287

Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

DEFF Research Database (Denmark)

Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

Science.gov (United States)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Cone-beam computed tomography imaging: therapeutic staff dose during chemoembolisation procedure

International Nuclear Information System (INIS)

Paul, Jijo; Vogl, Thomas J; Chacko, Annamma; Mbalisike, Emmanuel C

2014-01-01

Cone-beam computed tomography (CBCT) imaging is an important requirement to perform real-time therapeutic image-guided procedures on patients. The purpose of this study is to estimate the personal-dose-equivalent and annual-personal-dose from CBCT imaging during transarterial chemoembolisation (TACE). Therapeutic staff doses (therapeutic and assistant physician) were collected during 200 patient (65  ±  15 years, range: 40–86) CBCT examinations over six months. Absorbed doses were assessed using thermo-luminescent dosimeters during patient hepatic TACE therapy. We estimated personal-dose-equivalent (PDE) and annual-personal-dose (APD) from absorbed dose based on international atomic energy agency protocol. APD for therapeutic procedure was calculated (therapeutic physician: 5.6 mSv; assistant physician: 5.08 mSv) based on institutional work load. Regarding PDE, the hands of the staff members received a greater dose compared to other anatomical locations (therapeutic physician: 56 mSv, 72 mSv; assistant physician: 12 mSv, 14 mSv). Annual radiation doses to the eyes and hands of the staff members were lower compared to the prescribed limits by the International Commission on Radiological Protection (ICRP). PDE and APD of both therapeutic staff members were within the recommended ICRP-103 annual limit. Dose to the assistant physician was lower than the dose to the therapeutic physician during imaging. Annual radiation doses to eye-lenses and hands of both staff members were lower than prescribed limits. (paper)

Ondansetron. Therapeutic use as an antiemetic

Energy Technology Data Exchange (ETDEWEB)

Milne, R.J.; Heel, R.C. (Adis Drug Information Services, Auckland (New Zealand))

1991-04-01

Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs.

Ondansetron. Therapeutic use as an antiemetic

International Nuclear Information System (INIS)

Milne, R.J.; Heel, R.C.

1991-01-01

Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs

Therapeutic response to benzodiazepine in panic disorder subtypes

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Alexandre Martins Valença

Full Text Available CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day, compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001 and decrease in anxiety (p = 0.024. In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

Self-Control Strength Depletion Reduces Self-Efficacy and Impairs Exercise Performance.

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Graham, Jeffrey D; Bray, Steven R

2015-10-01

The purpose of this study was to investigate the role of task self-efficacy as a psychological factor involved in the relationship between self-control depletion and physical endurance. Participants (N = 37) completed two isometric handgrip endurance trials, separated by a Stroop task, which was either congruent (control) or incongruent (causing depletion). Task self-efficacy for the second endurance trial was measured following the Stroop task. Participants in the depletion condition reported lower task self-efficacy and showed a greater reduction in performance on the second endurance trial when compared with controls. Task self-efficacy also mediated the relationship between self-control depletion and endurance performance. The results of this study provide evidence that task self-efficacy is negatively affected following self-control depletion. We recommend that task self-efficacy be further investigated as a psychological factor accounting for the negative change in self-control performance of physical endurance and sport tasks following self-control strength depletion.

Increasing Memory Self-Efficacy and Strategy Use in Hispanic Elders.

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McDougall, Graham J

1998-01-01

This study tested the effects of a 4-week, nine-session group intervention taught in Spanish to Hispanic older adults entitled "Quieres Mejorar Tu Memoria" (Do you wish to improve your memory?). The program was based on Bandura's self-efficacy theory and was designed to increase memory self-efficacy and strategy use. A total of 33 older adults attending a senior center (mean--age = 69 years; education = 5 years; MMSE = 25) participated in the study. A booster session and a post-test were given at 3 months to the intervention group (n=22). At posttest the intervention reported greater confidence in preventing decline in their memories, and in particular greater use of the internal strategy of elaboration (2.99 vs. 3.41), and the external strategies of list (2.55 vs. 3.38) and note (3.27 vs. 3.75).

AN OVERVIEW OF BIOLOGICS: SCIENCE BEHIND PROTEIN THERAPEUTICS

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Inderjeet Kaur

2012-12-01

Full Text Available Biosimilars or ‘follow-on biologics’ are new biopharmaceutical agents that are ‘similar’ but not identical to a reference biopharmaceutical product. Biosimilars are considered ‘comparable’ to the reference product, but this does not ensure therapeutic equivalence. Inherent differences between biosimilars may produce dissimilarities in clinical efficacy, safety, and immunogenicity. Therefore accurate measurement and characterization of these differences and absolute quantification of biosimilars is the significant requirement at present. Mass spectrometry coupled with high performance liquid chromatography offers the most sensitive and accurate solution for this. This review discusses the potential strategies for the absolute quantification of biosimilars using mass spectrometry.

Current Status of Dengue Therapeutics Research and Development.

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Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

2017-03-01

Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

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

2017-01-01

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

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

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Julia A Loos

2017-02-01

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

The Jak2 Inhibitor, G6, Alleviates Jak2-V617F–Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow

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Annet Kirabo

2011-11-01

Full Text Available We recently developed a Janus kinase 2 (Jak2 small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F– mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F–mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F–mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6. In the liver, G6 eliminated Jak2-V617F–driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the spleno-megaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho–signal transducer and activator of transcription 5 (STAT5. It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67% on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F–mediated myeloproliferative neoplasia.

Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

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Sambola, A; Ferreira-González, I; Angel, J; Alfonso, F; Maristany, J; Rodríguez, O; Bueno, H; López-Minguez, J R; Zueco, J; Fernández-Avilés, F; San Román, A; Prendergast, B; Mainar, V; García-Dorado, D; Tornos, P

2009-09-01

To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. A prospective multicentre registry. In hospital, after discharge and follow-up by telephone call. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

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Moler, Frank W; Silverstein, Faye S; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Nadkarni, Vinay M; Meert, Kathleen L; Browning, Brittan; Pemberton, Victoria L; Page, Kent; Gildea, Marianne R; Scholefield, Barnaby R; Shankaran, Seetha; Hutchison, Jamie S; Berger, John T; Ofori-Amanfo, George; Newth, Christopher J L; Topjian, Alexis; Bennett, Kimberly S; Koch, Joshua D; Pham, Nga; Chanani, Nikhil K; Pineda, Jose A; Harrison, Rick; Dalton, Heidi J; Alten, Jeffrey; Schleien, Charles L; Goodman, Denise M; Zimmerman, Jerry J; Bhalala, Utpal S; Schwarz, Adam J; Porter, Melissa B; Shah, Samir; Fink, Ericka L; McQuillen, Patrick; Wu, Theodore; Skellett, Sophie; Thomas, Neal J; Nowak, Jeffrey E; Baines, Paul B; Pappachan, John; Mathur, Mudit; Lloyd, Eric; van der Jagt, Elise W; Dobyns, Emily L; Meyer, Michael T; Sanders, Ronald C; Clark, Amy E; Dean, J Michael

2017-01-26

Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse

Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part I: Curcumin.

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Di Martino, Rita Maria Concetta; Luppi, Barbara; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Abruzzo, Angela; Belluti, Federica

2017-05-01

curcumin is the main bioactive component contained in Curcuma Longa, largely employed in traditional medicine. Recently, beneficial properties, useful for prevention and treatment of several disorders, have been discovered for this compound. Peculiar structural feature is an α,β-unsaturated carbonyl system essential for establishing contacts with critical cysteine residues of several targets. This distinctive mechanism of action imparts to the molecule the ability to affect a large number of targets, accounting for its pleiotropic behaviour and definition of "privileged structure". Areas covered: The objective of the review is an examination of the recent developments in the field of the anti-cancer applications of curcumin, together with formulation issues, considering the patent literature in the years 2012-2016. Expert opinion: The wide therapeutic efficacy of curcumin is related to synergistic interactions with several biological targets, along with the modulation of several signaling pathways. This peculiar behaviour could be useful in the treatment of multifactorial diseases such as cancer. Combination of curcumin with a first line antineoplastic drug proved to be a valuable strategy to obtain an amplified response with minimized side effects. Innovative curcumin formulations based on the nanotechnology approach allowed improving both bioavailability and therapeutic efficacy.

Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients.

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Min, Sang-Il; Ha, Jongwon; Kim, Yon Su; Ahn, Sang Hyun; Park, Taejin; Park, Dae Do; Kim, Suh Min; Min, Seung-Kee; Hong, Hyejin; Ahn, Curie; Kim, Sang Joon

2013-12-01

There is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF Tacrolimus) in solid organ transplantation. A prospective, randomized study of 126 de novo renal transplant patients was conducted to compare the efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n = 63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition. Crossover study was carried out in 66 patients at 6 months. On Day 10, 117 patients completed PK profiles (54 GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C(0) (9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL, P = 0.80) but significantly higher dose-normalized C(max) (309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg, P PK profiles evaluated at 9 months showed that generic substitution also resulted in an 'early and high C(max)'. Efficacy and safety data were comparable over the 9-month study period. Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation.

Effects of a Rape Awareness Program on College Women: Increasing Bystander Efficacy and Willingness to Intervene

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Foubert, John D.; Langhinrichsen-Rohling, Jennifer; Brasfield, Hope; Hill, Brent

2010-01-01

An experimental study evaluated the efficacy of a sexual assault risk-reduction program on 279 college women that focused on learning characteristics of male perpetrators and teaching bystander intervention techniques. After seeing The Women's Program, participants reported significantly greater bystander efficacy and significantly greater…

Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

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Seung Taek Ji

2017-01-01

Full Text Available The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.

Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

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Danielle Maria Camelo Cid

2013-01-01

Full Text Available Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC. All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51% with ages rangingbetween 21 and 40 years (42%, from the countryside (59%, in the chronic phase (95%, with high-riskprognostic factors (40%; the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

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

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Ning, Shoucheng; Bednarski, Mark; Oronsky, Bryan; Scicinski, Jan; Knox, Susan J

2014-05-09

Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

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Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

2017-08-15

Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-β type I receptor inhibitor

International Nuclear Information System (INIS)

Taniguchi, Yukimi; Kawano, Kumi; Minowa, Takuya; Shimojo, Yuki; Maitani, Yoshie; Sugino, Takashi

2010-01-01

Tumor cell targeting of drug carriers is a promising strategy and uses the attachment of various ligands to enhance the therapeutic potential of chemotherapy agents. Folic acid is a high-affinity ligand for folate receptor, which is a functional tumor-specific receptor. The transforming growth factor (TGF)-β type I receptor (TβR-I) inhibitor A-83-01 was expected to enhance the accumulation of nanocarriers in tumors by changing the microvascular environment. To enhance the therapeutic effect of folate-linked liposomal doxorubicin (F-SL), we co-administrated F-SL with A-83-01. Intraperitoneally injected A-83-01-induced alterations in the cancer-associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F-SL combined with A-83-01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A-83-01 temporarily changed the tumor vasculature around 3 h post injection. A-83-01 induced 1.7-fold higher drug accumulation of F-SL in the tumor than liposome alone at 24 h post injection. Moreover F-SL co-administrated with A-83-01 showed significantly greater antitumor activity than F-SL alone. This study shows that co-administration of TβR-I inhibitor will open a new strategy for the use of folate receptor (FR)-targeting nanocarriers for cancer treatment. (author)

Culture, context and therapeutic processes: delivering a parent-child intervention in a remote Aboriginal community.

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Mares, Sarah; Robinson, Gary

2012-04-01

Little is written about the process of delivering mainstream, evidence-based therapeutic interventions for Aboriginal children and families in remote communities. Patterns of interaction between parents and children and expectations about parenting and professional roles and responsibilities vary across cultural contexts. This can be a challenging experience for professionals accustomed to work in urban settings. Language is only a part of cultural difference, and the outsider in a therapeutic group in an Aboriginal community is outside not only in language but also in access to community relationships and a place within those relationships. This paper uses examples from Let's Start, a therapeutic parent-child intervention to describe the impact of distance, culture and relationships in a remote Aboriginal community, on the therapeutic framework, group processes and relationships. Cultural and contextual factors influence communication, relationships and group processes in a therapeutic group program for children and parents in a remote Aboriginal community. Group leaders from within and from outside the community, are likely to have complementary skills. Cultural and contextual factors influence communication, relationships and group processes in a therapeutic group program for children and parents in a remote Aboriginal community. Group leaders from within and from outside the community, are likely to have complementary skills. Program adaptation, evaluation and staff training and support need to take these factors into account to ensure cultural accessibility without loss of therapeutic fidelity and efficacy.

Therapeutic Assessment for Preadolescent Boys with Oppositional Defiant Disorder: A Replicated Single-Case Time-Series Design

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Smith, Justin D.; Handler, Leonard; Nash, Michael R.

2010-01-01

The Therapeutic Assessment (TA) model is a relatively new treatment approach that fuses assessment and psychotherapy. The study examines the efficacy of this model with preadolescent boys with oppositional defiant disorder and their families. A replicated single-case time-series design with daily measures is used to assess the effects of TA and to…

Translational PKPD modeling in schizophrenia: linking receptor occupancy of antipsychotics to efficacy and safety

NARCIS (Netherlands)

Pilla Reddy, Venkatesh; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

2012-01-01

Objectives: To link the brain dopamine D2 receptor occupancy (D2RO) of antipsychotic drugs with clinical endpoints of efficacy and safety to assess the therapeutic window of D2RO. Methods: Pharmacokinetic-Pharmacodynamic (PK-PD) models were developed to predict the D2 receptor occupancy of

Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment

NARCIS (Netherlands)

Fineman, M.S.; Mace, K.F.; Diamant, M.; Darsow, T.; Cirincione, B.B.; Porter, T.K.B.; Kinninger, L.A.; Trautmann, M.E.

2012-01-01

Aims: Antibody formation to therapeutic peptides is common. This analysis characterizes the time-course and cross-reactivity of anti-exenatide antibodies and potential effects on efficacy and safety. Methods: Data from intent-to-treat patients in 12 controlled (n = 2225,12-52weeks) and 5

Ectromelia Virus Infections of Mice as a Model to Support the Licensure of Anti-Orthopoxvirus Therapeutics

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R. Mark Buller

2010-09-01

Full Text Available The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the “Animal Efficacy Rule”. One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. In this review we outline how mousepox has been used as a model for smallpox. We also discuss mousepox in the context of mouse strain, route of infection, infectious dose, disease progression, and recovery from infection.

Nitric oxide nanoparticles: Pre-clinical utility as a therapeutic for intramuscular abscesses

OpenAIRE

Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

2012-01-01

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine absce...

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

International Nuclear Information System (INIS)

Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

2012-01-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

Energy Technology Data Exchange (ETDEWEB)

Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

2012-11-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

Therapeutic effects of protein kinase N3 small interfering RNA and doxorubicin combination therapy on liver and lung metastases

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Hattori, Yoshiyuki; Kikuchi, Takuto; Nakamura, Mari; Ozaki, Kei-Ichi; Onishi, Hiraku

2017-01-01

It has been reported that suppression of protein kinase N3 (PKN3) expression in vascular and lymphatic endothelial cells results in the inhibition of tumor progression and lymph node metastasis formation. The present study investigated whether combination therapy of small interfering RNA (siRNA) against PKN3 and doxorubicin (DXR) could increase therapeutic efficacy against liver and lung metastases. In vitro transfection of PKN3 siRNA into PKN3-positive MDA-MB-231, LLC, and Colon 26 cells and PKN3-negative MCF-7 cells did not inhibit cell growth and did not increase sensitivity to DXR. However, following in vivo treatment, PKN3 siRNA suppressed the growth of liver MDA-MB-231 and lung LLC and MCF-7 metastases, although combination therapy with DXR did not increase the therapeutic efficacy. By contrast, in liver MCF-7 metastases, PKN3 siRNA or DXR alone did not exhibit significant inhibition of tumor growth, but their combination significantly improved therapeutic efficacy. Treatment of liver MDA-MB-231 metastases with PKN3 siRNA induced a change in vasculature structure via suppression of PKN3 mRNA expression. PKN3 siRNA may induce antitumor effects in lung and liver metastases by suppression of PKN3 expression in stroma cells, such as endothelial cells. From these findings, PKN3 siRNA alone or in combination with DXR may reduce the tumor growth of liver and lung metastases regardless of PKN3 expression in tumor cells. PMID:29098022

Curcumin Nanomedicine: A Road to Cancer Therapeutics

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Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

2013-01-01

Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

International Nuclear Information System (INIS)

Waters, Katrina M.; Sontag, Ryan L.; Weber, Thomas J.

2013-01-01

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

Energy Technology Data Exchange (ETDEWEB)

Waters, Katrina M. [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA 99354 (United States); Sontag, Ryan L. [Systems Toxicology Groups, Pacific Northwest National Laboratory, Richland, WA 99354 (United States); Weber, Thomas J., E-mail: Thomas.Weber@pnl.gov [Systems Toxicology Groups, Pacific Northwest National Laboratory, Richland, WA 99354 (United States)

2013-04-15

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response.

CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

Directory of Open Access Journals (Sweden)

Diana Rosa Fernández Ruiz

2017-02-01

Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

Antibacterial Efficacy of Polysaccharide Capped Silver Nanoparticles Is Not Compromised by AcrAB-TolC Efflux Pump

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Mitali Mishra

2018-05-01

Full Text Available Antibacterial therapy is of paramount importance in treatment of several acute and chronic infectious diseases caused by pathogens. Over the years extensive use and misuse of antimicrobial agents has led to emergence of multidrug resistant (MDR and extensive drug resistant (XDR pathogens. This drastic escalation in resistant phenotype has limited the efficacy of available therapeutic options. Thus, the need of the hour is to look for alternative therapeutic approaches to mitigate healthcare concerns caused due to MDR bacterial infections. Nanoparticles have gathered much attention as potential candidates for antibacterial therapy. Equipped with advantages of, wide spectrum bactericidal activity at very low dosage, inhibitor of biofilm formation and ease of permeability, nanoparticles have been considered as leading therapeutic candidates to curtail infections resulting from MDR bacteria. However, substrate non-specificity of efflux pumps, particularly those belonging to resistance nodulation division super family, have been reported to reduce efficacy of many potent antibacterial therapeutic drugs. Previously, we had reported antibacterial activity of polysaccharide-capped silver nanoparticles (AgNPs toward MDR bacteria. We showed that AgNPs inhibits biofilm formation and alters expression of cytoskeletal proteins FtsZ and FtsA, with minimal cytotoxicity toward mammalian cells. In the present study, we report no reduction in antibacterial efficacy of silver nanoparticles in presence of AcrAB-TolC efflux pump proteins. Antibacterial tests were performed according to CLSI macrobroth dilution method, which revealed that both silver nanoparticles exhibited bactericidal activity at very low concentrations. Further, immunoblotting results indicated that both the nanoparticles modulate the transporter AcrB protein expression. However, expression of the membrane fusion protein AcrA did show a significant increase after exposure to AgNPs. Our results

[Therapeutic massage on behavioral disturbances of elderly patients with dementia].

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Barquilla Ávila, Carolina; Rodríguez-Mansilla, Juan

2015-12-01

To know the efficacy of therapeutic massage on behavioral disturbances of elderly patients with dementia. Literature review. The literature search was done in six scientific databases: PubMed, Cochrane Library Plus, PEDro, Dialnet, Scopus and CSIC, between 1983 and 2013. The search terms were "massage", "dementia", "therapy", "behavior disorders" and "Alzheimer". Of the 496 articles analyzed, 11 scientific articles have met the selection criteria. Inclusion criteria were: clinical trials, published in English or Spanish, which had analyzed the effects of massage therapy on altered behaviors in people with dementia. The variables were massage benefits, type of massage and massage lubricant. Their authors use different massage techniques (effleurage, pétrissage, pressures, frictions and kneading), obtain better conduct disorders (aggression, anxiety, agitation, and resistance to care) of elderly. The therapeutic massage can be a complementary treatment in the rehabilitation program for better behavior disorders. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Therapeutic potential of gel-based injectables for vocal fold regeneration

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Bartlett, Rebecca S.; Thibeault, Susan L.; Prestwich, Glenn D.

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. PMID:22456756

Therapeutic potential of gel-based injectables for vocal fold regeneration

International Nuclear Information System (INIS)

Bartlett, Rebecca S; Thibeault, Susan L; Prestwich, Glenn D

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. (paper)

Increasing efficacy and reducing systemic absorption of brimonidine tartrate ophthalmic gels in rabbits.

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Pang, Xiaochen; Li, Jiawei; Pi, Jiaxin; Qi, Dongli; Guo, Pan; Li, Nan; Wu, Yumei; Liu, Zhidong

2018-03-01

Systemic absorption of ocularly administered Brimonidine Tartrate has been reported to give rise to several side-effects. Hence, it has become crucial to develop a delivery system that could increase efficacy and reduce systemic absorption. Therefore, the present work aims to develop Brimonidine Tartrate gels with different concentrations (0.05%, 0.1%, and 0.2% w/v, respectively) using Carbopol 974 P and HPMC E4M, and compare the therapeutic efficacy and systemic absorption with that of eye drop (0.2%, w/v) by UPLC-MS/MS. The result of histological analysis did not show any morphological or structural changes after the administration of formulations. In vitro residence time studies demonstrated that the gels exhibited a better precorneal residence time as compared with the eye drop. The gels with lower concentrations of the drug (0.05% and 0.1%, w/v) could significantly decrease intraocular pressure (IOP) in both normal and water-loaded rabbits as compared to the eye drop. Finally, the values of the ratio of AUC (0→∞) in comparison to eye drop showed the gels with lower concentrations of Brimonidine Tartrate could decrease the systemic absorption. From the result, it can be concluded the 0.1% ophthalmic gel has a potential to improve therapeutic efficacy and reduce the potential toxicity caused by systemic absorption.

Garlic: a review of potential therapeutic effects

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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

Perceived efficacy of analgesic drug regimens used for koalas (Phascolarctos cinereus) in Australia.

Science.gov (United States)

de Kauwe, Tyron; Kimble, Benjamin; Govendir, Merran

2014-06-01

Recent publications report that some therapeutic drugs used in koalas (Phascolarctos cinereus) have poor oral absorption and are rapidly eliminated. Therefore, information on both the analgesic drug dosage regimens used to treat koalas in Australia and koala caretakers' perceptions of the efficacy of these drugs to control pain was collected for the purpose of identifying the most popular analgesics to prioritize future analgesic pharmacokinetic studies for this species. A one-page, double-sided questionnaire was distributed both electronically and by mail to Australian koala care facilities such as zoos and wildlife hospitals. Information was received from 13 respondents. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently used analgesics, followed by full micro- and partial opioid receptor agonists and acetaminophen with or without codeine. The full micro-opioid receptor agonists and acetaminophen with or without codeine were most consistently considered efficacious, with wider variation in perceived efficacy of the NSAIDs. Analgesic drug combinations were generally thought efficacious.

Self-Efficacy versus Perceived Enjoyment as Predictors of Physical Activity Behavior

Science.gov (United States)

Lewis, Beth A.; Williams, David M.; Frayeh, Amanda L.; Marcus, Bess H.

2015-01-01

Objective Self-efficacy and physical activity (PA) enjoyment are related to PA behavior, but it is unclear which is more important and how they interrelate. The purpose of this study was to examine how these two constructs interrelate to influence PA behavior. Design Participants were low active adults (n=448) participating in a RCT examining the effect of a PA promotion intervention. Participants completed physical activity, enjoyment, and self-efficacy measures at baseline, six, and 12 months. Results Self-efficacy and enjoyment at both baseline and six months predicted PA at 12 months. However, enjoyment was a stronger predictor than self-efficacy in that self-efficacy no longer predicted PA behavior when included alongside enjoyment. In follow-up mediation analyses, enjoyment at six months did not mediate the effect of baseline self-efficacy on 12-month PA; however, six-month self-efficacy mediated the effect of baseline enjoyment on 12-month PA. Conclusion Our results indicate that interventions should perhaps initially focus on increasing enjoyment of physical activity. Greater PA enjoyment appears to influence individuals’ self-reported ability to engage in regular PA (i.e., higher self-efficacy ratings). Additional research is needed to better understand the interrelationships between self-efficacy and enjoyment and how these constructs affect PA. PMID:26541890

Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi from Ghana and Gabon

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Kreuels Benno

2008-10-01

Full Text Available Abstract Background Intermittent preventive treatment in infants (IPTi with sulphadoxine-pyrimethamine (SP reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Methods Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Results Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. Conclusion The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Trial registration Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial and NCT ID # 00167843 (Lambaréné Trial, http://www.clinicaltrials.gov.

Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

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Marriott, Anthony C; Dove, Brian K; Whittaker, Catherine J; Bruce, Christine; Ryan, Kathryn A; Bean, Thomas J; Rayner, Emma; Pearson, Geoff; Taylor, Irene; Dowall, Stuart; Plank, Jenna; Newman, Edmund; Barclay, Wendy S; Dimmock, Nigel J; Easton, Andrew J; Hallis, Bassam; Silman, Nigel J; Carroll, Miles W

2014-01-01

Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

Directory of Open Access Journals (Sweden)

Anthony C Marriott

Full Text Available Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09 induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu and low (102 pfu doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

Self-efficacy and arthritis disability: An updated synthesis of the evidence base and its relevance to optimal patient care

Science.gov (United States)

2014-01-01

Self-efficacy, denoting the degree of confidence an individual has in carrying out a specific activity, was initially discussed in the 1970s as a potential correlate of disease outcomes. Drawn from 35 years of related research, this review provides an updated understanding of the concept of self-efficacy and its relevance for arthritis management. There is a consistent link between self-efficacy, arthritis pain and disability, and adherence to recommended therapeutic strategies. A wide variety of intervention strategies improve arthritis self-efficacy, as well as outcomes. Steps to assess and intervene thoughtfully to maximize self-efficacy beliefs are likely to impact arthritis disability outcomes quite favorably and significantly, regardless of disease type, duration, or sociodemographic factors. PMID:28070346

Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

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Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

2017-08-15

Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

The Efficacy of Lavender Aromatherapy in Reducing Preoperative Anxiety in Ambulatory Surgery Patients Undergoing Procedures in General Otolaryngology

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Wotman, Michael; Levinger, Joshua; Leung, Lillian; Kallush, Aron; Mauer, Elizabeth

2017-01-01

Background Preoperative anxiety is a common problem in hospitals and other health care centers. This emotional state has been shown to negatively impact patient satisfaction and outcomes. Aromatherapy, the therapeutic use of essential oils extracted from aromatic plants, may offer a simple, low‐risk and cost‐effective method of managing preoperative anxiety. The purpose of this study was to evaluate the efficacy of lavender aromatherapy in reducing preoperative anxiety in ambulatory surgery patients undergoing procedures in general otolaryngology. Methods A prospective and controlled pilot study was conducted with 100 patients who were admitted to New York‐Presbyterian/Weill Cornell Medical Center for ambulatory surgery from January of 2015 to August of 2015. The subjects were allocated to two groups; the experimental group received inhalation lavender aromatherapy in the preoperative waiting area while the control group received standard nursing care. Both groups reported their anxiety with a visual analog scale (VAS) upon arriving to the preoperative waiting area and upon departure to the operating room. Results According to a Welch's two sample t‐test, the mean reduction in anxiety was statistically greater in the experimental group than the control group (p = 0.001). Conclusion Lavender aromatherapy reduced preoperative anxiety in ambulatory surgery patients. This effect was modest and possibly statistically significant. Future research is needed to confirm the clinical efficacy of lavender aromatherapy. Level of Evidence 2b PMID:29299520

Therapeutic efficacy of aldoxorubicin in an intracranial xenograft mouse model of human glioblastoma.

Science.gov (United States)

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

2014-10-01

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

The Relationship between Therapeutic Alliance and Service User Satisfaction in Mental Health Inpatient Wards and Crisis House Alternatives: A Cross-Sectional Study

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Sweeney, Angela; Fahmy, Sarah; Nolan, Fiona; Morant, Nicola; Fox, Zoe; Lloyd-Evans, Brynmor; Osborn, David; Burgess, Emma; Gilburt, Helen; McCabe, Rosemarie; Slade, Mike; Johnson, Sonia

2014-01-01

Background Poor service user experiences are often reported on mental health inpatient wards. Crisis houses are an alternative, but evidence is limited. This paper investigates therapeutic alliances in acute wards and crisis houses, exploring how far stronger therapeutic alliance may underlie greater client satisfaction in crisis houses. Methods and Findings Mixed methods were used. In the quantitative component, 108 crisis house and 247 acute ward service users responded to measures of satisfaction, therapeutic relationships, informal peer support, recovery and negative events experienced during the admission. Linear regressions were conducted to estimate the association between service setting and measures, and to model the factors associated with satisfaction. Qualitative interviews exploring therapeutic alliances were conducted with service users and staff in each setting and analysed thematically. Results We found that therapeutic alliances, service user satisfaction and informal peer support were greater in crisis houses than on acute wards, whilst self-rated recovery and numbers of negative events were lower. Adjusted multivariable analyses suggest that therapeutic relationships, informal peer support and negative experiences related to staff may be important factors in accounting for greater satisfaction in crisis houses. Qualitative results suggest factors that influence therapeutic alliances include service user perceptions of basic human qualities such as kindness and empathy in staff and, at service level, the extent of loss of liberty and autonomy. Conclusions and Implications We found that service users experience better therapeutic relationships and higher satisfaction in crisis houses compared to acute wards, although we cannot exclude the possibility that differences in service user characteristics contribute to this. This finding provides some support for the expansion of crisis house provision. Further research is needed to investigate why acute

Safety and efficacy of Labisia pumila containing products

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Muhammad Syafiq Saleh

2016-01-01

Full Text Available Labisia pumila is a traditional medicinal plant which has wide therapeutic application including induction of labor and treatment of dysentery, dysmenorrhea and gonorrhea. We aimed for systematic review of the efficacy andsafety of L. pumila extract or its other commercial products availabe in Malaysian market. The marketed 500 mg capsule is composed of 40 mg L. pumila, 10 mg C. caudatum extract and 450 mg excipient. The commercial products did not follow the registration guidelines of Malaysian National Pharmaceutical Control Bureau (NPCB and advertisement guidelines of Malaysian Advertisement Board. Randomized, placebo controlled clinical trials reported the safe consumpotion of L. pumila water extract on postmanoposal women. Information on the efficacy and safety of commercial products are not sufficiently available. Many unregistered products (mostly capsule form are flooded in Malaysian market without having scientific information. Consumption of those products may seriously impair the health of the people.

Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks.

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Mah, Li-Jeen; Orlowski, Christian; Ververis, Katherine; Vasireddy, Raja S; El-Osta, Assam; Karagiannis, Tom C

2011-01-25

Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds.

The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.

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Justin Stebbing

Full Text Available Analysis of circulating tumor cells (CTCs provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43% individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.Clinical trials.gov NCT00820924.

Canonical and non-canonical barriers facing antimiR cancer therapeutics.

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Cheng, Christopher J; Saltzman, W Mark; Slack, Frank J

2013-01-01

Once considered genetic "oddities", microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms-ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles-are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.

Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis

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Judith M. Ball

2015-01-01

Full Text Available Rotavirus (RV infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

Short-term therapeutic role of zinc in children infection.

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Das, Rashmi Ranjan; Singh, Meenu; Shafiq, Nusrat

2012-09-01

In contrast to its 'preventive role', no consensus has evolved for the therapeutic role of zinc in pneumonia in children. We conducted a meta-analysis to find the therapeutic role of zinc in children infection (ALRTI). A comprehensive search was performed of the major electronic databases. Randomised controlled trials (RCTs) comparing treatment with zinc versus placebo were included. Seven RCTs (1066 subjects) conducted in developing countries were eligible for inclusion. There was no significant difference between the two groups regarding the time of resolution of severe illness (standardised mean difference (SMD) -0.15 (95% confidence interval (CI) -0.5, 0.2; p=0.4)) and duration of hospitalisation (SMD -0.29 (95% CI -0.68, -0.09; p=0.13)). No significant difference between the two groups was also noted for other parameters (duration of resolution of hypoxia, chest indrawing or tachypnoea, change of antibiotics and treatment failure rates). The adverse events were not significant. To conclude, present available data do not support the efficacy of zinc in treatment of severe ALRTI. Copyright © 2012 Elsevier Ltd. All rights reserved.

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

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Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

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Wasserman, Sean; Meintjes, Graeme; Maartens, Gary

2016-10-01

Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

Therapeutic potential of bryophytes and derived compounds against cancer

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Abhijit Dey

2015-08-01

Full Text Available Bryophytes, taxonomically placed between the algae and the pteridophytes, are divided into three classes such as Liverworts, Hornworts and Mosses. Indigenous use involves this small group of plants to treat various diseases. Bryophytes have been investigated pharmacologically for active biomolecules. Several constituents with therapeutic potential have been isolated, characterized and investigated for antibacterial, antifungal, antiviral, antioxidative, antiinflamatory and anticancerous efficacy. The present review deals with the literature covering the anticancerous potential of bryophytes. Apart from the examples of the compounds and the containing bryophyte genera, the authors have tried to include the examples of cancer cell lines on which the efficacy have been tested and the mode of action of certain cytotoxic agents. Crude extracts and isolated compounds from bryophytes were found to possess potent cytotoxic properties. Different types of terpenoids and bibenzyls have been reported among the most potent cytotoxic compounds. Most of these compounds were found to induce apoptosis by activating a number of genes and enzymes. Biochemical markers such as DNA fragmentation, nuclear condensation, proteolysis of poly (ADP-ribose polymerase, activation of caspases, inhibition of antiapoptotic nuclear transcriptional factor-kappaB, activation of p38 mitogen-activated protein kinase etc. have been found to be associated with apoptotic and necrotic response. This review summarizes recent scientific findings and suggests further investigations to evaluate the cytotoxic efficacy of bryophytes.

Efficacy of Creative Clay Work for Reducing Negative Mood: A Randomized Controlled Trial

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Kimport, Elizabeth R.; Robbins, Steven J.

2012-01-01

Clay work has long been used in art therapy to achieve therapeutic goals. However, little empirical evidence exists to document the efficacy of such work. The present study randomly assigned 102 adult participants to one of four conditions following induction of a negative mood: (a) handling clay with instructions to create a pinch pot, (b)…

[Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus].

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Ciotta, L; Pagano, I; Stracquadanio, M; Di Leo, S; Andò, A; Formuso, C

2011-06-01

The premenstrual dysphoric disorder (PMDD) is one of the main problems of the premenstrual phase. It consists of symptoms that sometimes invalidate the scope of employment, social and psycho-affective of patients, requiring thus a diagnostic and therapeutic approach as detailed and accurate as possible. The therapeutic strategies available for this disease are many, but recently the emphasis has been on Vitex agnus castus (VAC), considered by many as evidence drug of choice for both PMS and for the PMDD, being with satisfactory therapeutic properties and small side effects. Our study evaluated a group of patients suffering from PMDD and the clinical efficacy of treatment with VAC (and compared the effectiveness of the results of a more homogeneous group of patients treated with fluoxetine). This study confirms the data reported in the literature regarding the effectiveness of VAC therapy with no side effects.

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

NARCIS (Netherlands)

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

2014-01-01

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

Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP

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Barrio, G.; Dias, C.R.B.R.; Osso Junior, J.A., E-mail: gracielabarrio@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2012-07-01

Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/beta radionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving the normal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is based on information obtained in dosimetric studies. Beta emitting radionuclides such as {sup 131}I, {sup 188}Re, {sup 90}Y, {sup 177}Lu and {sup 166}Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) is a chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkin lymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeutic efficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDA approval for NHL treatment: {sup 131}I-AntiCD20 (Bexar) and {sup 90}Y-AntiCD20 (Zevalin). Techniques for the radiolabeling of {sup 188}Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluate the clinical use of this radionuclide in particular. The use of {sup 188}Re (T{sub 1/2} 17h) produced by the decay of {sup 188}W (T{sub 1/2} 69d), from an {sup 188}W/{sup 188}Re generator system, has represented an alternative to RIT. Beyond high energy beta emission for therapy, {sup 188}Re also emits gamma rays (155keV) suitable for image. The aim of this new project is to compare the labeling of anti-CD20 with {sup 188}Re with the same MAb labeled with {sup 131}I, {sup 177}Lu, {sup 90}Y and even {sup 99m}Tc. The first step in this project is the review of the published data available concerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN, taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities and biodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platform through VB.NET and C{sup ++} for biodistribution and dosimetric

Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

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Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

2009-02-01

In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

A unique carrier for delivery of therapeutic compounds beyond the blood-brain barrier.

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Delara Karkan

Full Text Available BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin, across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX or adriamycin (ADR and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders

The efficacy of cognitive-behavioral therapy for eating disorders: A systematic review and meta-analysis.

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Linardon, Jake; Wade, Tracey D; de la Piedad Garcia, Xochitl; Brennan, Leah

2017-11-01

This meta-analysis examined the efficacy of cognitive-behavioral therapy (CBT) for eating disorders. Randomized controlled trials of CBT were searched. Seventy-nine trials were included. Therapist-led CBT was more efficacious than inactive (wait-lists) and active (any psychotherapy) comparisons in individuals with bulimia nervosa and binge eating disorder. Therapist-led CBT was most efficacious when manualized CBT-BN or its enhanced version was delivered. No significant differences were observed between therapist-led CBT for bulimia nervosa and binge eating disorder and antidepressants at posttreatment. CBT was also directly compared to other specific psychological interventions, and therapist-led CBT resulted in greater reductions in behavioral and cognitive symptoms than interpersonal psychotherapy at posttreatment. At follow-up, CBT outperformed interpersonal psychotherapy only on cognitive symptoms. CBT for binge eating disorder also resulted in greater reductions in behavioral symptoms than behavioral weight loss interventions. There was no evidence that CBT was more efficacious than behavior therapy or nonspecific supportive therapies. CBT is efficacious for eating disorders. Although CBT was equally efficacious to certain psychological treatments, the fact that CBT outperformed all active psychological comparisons and interpersonal psychotherapy specifically, offers some support for the specificity of psychological treatments for eating disorders. Conclusions from this study are hampered by the fact that many trials were of poor quality. Higher quality RCTs are essential. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Self-controlled learning benefits: exploring contributions of self-efficacy and intrinsic motivation via path analysis.

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Ste-Marie, Diane M; Carter, Michael J; Law, Barbi; Vertes, Kelly; Smith, Victoria

2016-09-01

Research has shown learning advantages for self-controlled practice contexts relative to yoked (i.e., experimenter-imposed) contexts; yet, explanations for this phenomenon remain relatively untested. We examined, via path analysis, whether self-efficacy and intrinsic motivation are important constructs for explaining self-controlled learning benefits. The path model was created using theory-based and empirically supported relationships to examine causal links between these psychological constructs and physical performance. We hypothesised that self-efficacy and intrinsic motivation would have greater predictive power for learning under self-controlled compared to yoked conditions. Participants learned double-mini trampoline progressions, and measures of physical performance, self-efficacy and intrinsic motivation were collected over two practice days and a delayed retention day. The self-controlled group (M = 2.04, SD = .98) completed significantly more skill progressions in retention than their yoked counterparts (M = 1.3, SD = .65). The path model displayed adequate fit, and similar significant path coefficients were found for both groups wherein each variable was predominantly predicted by its preceding time point (e.g., self-efficacy time 1 predicts self-efficacy time 2). Interestingly, the model was not moderated by group; thus, failing to support the hypothesis that self-efficacy and intrinsic motivation have greater predictive power for learning under self-controlled relative to yoked conditions.

Health Self-Efficacy Among Populations with Multiple Chronic Conditions: the Value of Patient-Centered Communication.

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Finney Rutten, Lila J; Hesse, Bradford W; St Sauver, Jennifer L; Wilson, Patrick; Chawla, Neetu; Hartigan, Danielle B; Moser, Richard P; Taplin, Stephen; Glasgow, Russell; Arora, Neeraj K

2016-08-01

Using cross-sectional survey data, we assessed the association between chronic illness burden and health-related self-efficacy, evaluating whether patient-centered communication is associated with self-efficacy and if that relationship varies by chronic illness burden. Data were from the Health Information National Trends Survey, a cross-sectional survey of the US adult population collected in 2012-2013 (n = 3630). Health-related self-efficacy was measured with the item: "Overall, how confident are you about your ability to take good care of your health?" and the prevalence of six chronic conditions and depression/anxiety was assessed. Patient-centered communication was measured as the frequency with which respondents perceived their healthcare providers allowed them to ask questions, gave attention to their emotions, involved them in decisions, made sure they understood how to take care of their health, helped them to deal with uncertainty, and if they felt they could rely on their healthcare providers to take care of their healthcare needs. Health-related self-efficacy was significantly lower among individuals with greater illness burden. In adjusted analysis, individuals who experienced more positive patient-centered communication reported higher levels of self-efficacy (β = 0.26, P self-efficacy were observed among patients reporting more positive patient-centered communication; the observed association was stronger among those with greater chronic illness burden.

Pharmacokinetics, Tissue Distribution and Therapeutic Effect of Cationic Thermosensitive Liposomal Doxorubicin Upon Mild Hyperthermia

OpenAIRE

Dicheva, Bilyana M.; Seynhaeve, Ann L. B.; Soulie, Thomas; Eggermont, Alexander M. M.; ten Hagen, Timo L. M.; Koning, Gerben A.

2015-01-01

textabstractPurpose: To evaluate pharmacokinetic profile, biodistribution and therapeutic effect of cationic thermosensitive liposomes (CTSL) encapsulating doxorubicin (Dox) upon mild hyperthermia (HT). Methods: Non-targeted thermosensitive liposomes (TSL) and CTSL were developed, loaded with Dox and characterized. Blood kinetics and biodistribution of Dox-TSL and Dox-CTSL were followed in B16BL6 tumor bearing mice upon normothermia (NT) or initial hyperthermia conditions. Efficacy study in B...

Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

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Yu Chih-Chieh

2012-05-01

Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

CIMAvax-EGF®, new therapeutic alternative for lung cancer: its application in Cienfuegos

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Yoana Herrera Leiva

2017-04-01

Full Text Available In 2016, the EGF-Predictor Phase IV Clinical Trial Opening Workshop was held in Cienfuegos, sponsored by the Center for Molecular Immunology of Havana which coexist with other clinical trials. The overall objective of the study is to evaluate the safety and efficacy of the CIMAVAX-EGF therapeutic vaccine for the treatment of patients diagnosed with lung cancer in advanced stages of the disease and, within its specific objectives, to assess overall survival and the treated patients’ life quality.

Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

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Laura S Stone

Full Text Available Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs. Analgesics acting at α2ARs and opioid receptors (ORs frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C. Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic

Therapeutic Effects of Horseback Riding Therapy on Gross Motor Function in Children with Cerebral Palsy: A Systematic Review

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Whalen, Cara N.; Case-Smith, Jane

2012-01-01

Purpose: This systematic review examined the efficacy of hippotherapy or therapeutic horseback riding (THR) on motor outcomes in children with cerebral palsy (CP). Methods: Databases were searched for clinical trials of hippotherapy or THR for children with CP. Results: Nine articles were included in this review. Although the current level of…

Efficacy of intrathecal baclofen delivery in the management of severe spasticity in upper motor neuron syndrome

NARCIS (Netherlands)

Rietman, Johan Swanik; Geertzen, J.H.B.

In the treatment of patients with severe spasticity, intrathecal administration of baclofen (ITB) was introduced in order to exert its effect directly at the receptor sites in the spinal cord, and have better therapeutic efficacy with smaller drug doses compared to oral antispasmodic medications.

Therapeutic targeting strategies using endogenous cells and proteins.

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Parayath, Neha N; Amiji, Mansoor M

2017-07-28

Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

Therapeutic applications of histone deacetylase inhibitors in sarcoma.

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Tang, Fan; Choy, Edwin; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

2017-09-01

Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and therapeutic application of internally emitting radiopharmaceuticals

International Nuclear Information System (INIS)

Adelstein, S.J.; Bloomer, W.D.

1980-01-01

This project is concerned with developing the potential of alpha-emitting radionuclides as agents for radiotherapy. Among the available α-emitters, astatine-211 appears most promising for testing the efficacy of α-emitters for therapeutic applications because: (1) it has some chemical similarities to iodine, an element that can readily be incorporated into numerous proteins and peptides; (2) it has a half life that is long enough to permit chemical manipulation yet short enough to minimize destruction of healthy cells; and (3) α-emission is associated with 100% of its decays. If appropriate biological carriers can be labeled with an alpha emitter such as 211 At, they could be of great utility in several areas of therapeutic medicine where elimination of specific cell populations is desired. While previous attempts to astatinate proteins using standard iodination techniques have been unsuccessful, effective labeling of proteins with astatine by first synthesizing an aryl astatide and then coupling this compound to the protein via an acylation has been achieved. Undergoing current investigation are several different aryl astatide-followed-by-acylation approaches including an astatinated Bolton-Hunter type reagent using concanavalin A (ConA) and melanocyte stimulating hormone (MSH) as model compounds

Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

International Nuclear Information System (INIS)

Togo, Shinsaku; Polanska, Urszula M.; Horimoto, Yoshiya; Orimo, Akira

2013-01-01

Human carcinomas frequently exhibit significant stromal reactions such as the so-called “desmoplastic stroma” or “reactive stroma”, which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies

Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

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Alireza eFaridar

2011-12-01

Full Text Available Therapeutic hypothermia (TH is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS and traumatic brain injury (TBI, however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention.Among the various methods for hypothermia induction, intravascular cooling (IVC may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.

Nuclear data for the production of therapeutic radionuclides. Summary report of first research coordination meeting

International Nuclear Information System (INIS)

Sublet, J.-Ch.; Paviotti-Corcuera, R.

2003-06-01

Presentations, discussions and conclusions from the First Co-ordination Meeting on Nuclear Data for the Production of Therapeutic Radionuclides are summarised in this report. The main purpose of the meeting was to discuss scientific and technical matters related to the subject and to co-ordinate related tasks. Programmes of work were agreed and assigned, and deadlines were set. Participants emphasized the importance of the completeness and accuracy of the resulting nuclear data for the production of these radionuclides to appropriate specific activities and purity along with the relevant decay data. The recommended data from this Coordinated Research Project should meet the requirements for the safe and efficacious application of therapeutic treatments in nuclear medicine. (author)

Development of the Fibulin-3 protein therapeutics of non small cell lung cancer stem cells

Energy Technology Data Exchange (ETDEWEB)

Kim, In Gyu; Kim, Kugchan; Jung, Il Lae; Kim, Seo Yeon; Choi, Su Im; Lee, Jae Ha

2013-09-15

This study focuses on developing an efficient bioprocess for large-scale production of fibulin-3 using Chinese Hamster Ovary cell expression system and evaluating its therapeutic potential for the treatment of cancer. The specific aims are as follows: Isolation and establishment of CSCs using FACS based on cell surface markers and high ALDH1 activity. Identification and characterization of lung cancer stem cells that acquire features of CSC upon exposure to ionizing radiation. Evaluation of the fibulin-3 effects on the stem traits and signaling pathways required for the generation and maintenance of CSCs. In vivo validation of fivulin-3 for tumor prognosis and therapeutic efficacy against lung cancer using animal model.

Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

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Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

2016-07-01

Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

Mediated and Moderated Effects of Neurocognitive Impairment on Outcomes of Treatment for Substance Dependence and Major Depression

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Worley, Matthew J.; Tate, Susan R.; Granholm, Eric; Brown, Sandra A.

2015-01-01

Objective Neurocognitive impairment has not consistently predicted substance use treatment outcomes but has been linked to proximal mediators of outcome. These indirect effects have not been examined in adults with substance dependence and co-occurring psychiatric disorders. We examined mediators and moderators of the effects of neurocognitive impairment on substance use among adults in treatment for alcohol or drug dependence and major depression (MDD). Method Participants were veterans (N =197, mean age = 49.3 years, 90% male, 75% Caucasian) in a trial of two group interventions for alcohol/drug dependence and MDD. Measures examined here included intake neurocognitive assessments and percent days drinking (PDD), percent days using drugs (PDDRG), self-efficacy, 12-step affiliation, and depressive symptoms measured every 3 months from intake to the 18-month follow-up. Results Greater intake neurocognitive impairment predicted lower self-efficacy, lower 12-step affiliation, and greater depression severity, and these time-varying variables mediated the effects of impairment on future PDD and PDDRG. The prospective effects of 12-step affiliation on future PDD were greater for those with greater neurocognitive impairment. Impairment also interacted with depression to moderate the effects of 12-step affiliation and self-efficacy on PDD. Adults with greater impairment and currently severe depression had the strongest associations between 12-step affiliation/self-efficacy and future drinking. Conclusions Greater neurocognitive impairment may lead to poorer outcomes from group therapy for alcohol/drug dependence and MDD due to compromised change in therapeutic processes. Distal factors such as neurocognitive impairment can interact with dynamic risk factors to modulate the association between therapeutic processes and future drinking outcomes. PMID:24588403

Children's Decision-Making Involvement About Research Participation: Associations With Perceived Fairness and Self-Efficacy.

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Miller, Victoria A; Feudtner, Chris; Jawad, Abbas F

2017-04-01

The primary objective of this study was to examine the associations of children's involvement in decisions about research participation with their perceptions of the decision-making process and self-efficacy. Participants were children (ages 8-17) who enrolled in research studies in the prior 2 months. Children completed a questionnaire that yielded three decision-making involvement subscales: Researcher Engages Child, Researcher Supports Autonomy, and Child Participates. Children reported on fairness of the decision-making process and health-related decision self-efficacy. After adjusting for age, higher scores on Researcher Engages Child were associated with greater self-efficacy, and higher scores on Researcher Supports Autonomy were associated with greater perceived fairness. These data underscore the potential importance of researcher-child interactions about research participation when assent is sought, including proactively involving children in the decision by asking for their opinions and communicating their central role in the decision, which are likely to be more meaningful to children than receiving information or signing a form.

III Frontier of accurate diagnosis of breast cancer. 1. Present state and prospect of preoperative diagnosis of progression, differential diagnosis of benign and malign natures, and efficacy evaluation of neoadjuvant chemotherapy. 2) Clinical efficacy and problem of FDG-PET (PET/CT) in breast cancer

International Nuclear Information System (INIS)

Kitajima, Kazuhiro; Kaji, Yasushi; Hayashi, Mitsuhiro; Sunagawa, Masakatsu; Murakami, Kouji; Yamazaki, Erena

2008-01-01

On authors' experience and literature, clinical efficacy and limitation of fluorodeoxyglucose-positron emission tomography (FDG-PET) (PET/CT) in the breast cancer are described and discussed for detection of the primary lesion, preoperative staging and lymph node diagnosis, diagnosis of recurrence and remote metastasis, evaluation of therapeutic efficacy, and prediction of prognosis. For routine breast cancer screening, authors think PET/CT is not always effective because of many false positive/negative findings. PET/CT and subsequent CT with iodine contrast media are thought to be useful for preoperative staging and planning in conservative surgery though detection of micro-metastatic nodes are often difficult. PET is reportedly superior to 99m Tc-MDP scintigraphy in bone metastasis detection, but which conceivably depends on the nature (osteogenic/osteolytic) of the lesion. For recurrence and remote metastasis, the diagnostic sensitivity, specificity and accuracy of PET/CT are reported to be as high as 84-98, 84-94 and 86-97%, respectively. Standardization of PET/CT monitoring is now necessary to evaluate the therapeutic efficacy. SUV which indicates the degree of FDG accumulation in the lesion, can be used for prediction of prognosis in future. Awaited is the development of more effective PET/CT apparatus and agent (instead of FDG) for detection of small metastatic lesions, axillary lymphatic metastasis, and viable focus after therapeutic treatments. (R.T.)

Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels - A platform for therapeutic delivery to mucosal sinus tissue.

Science.gov (United States)

Pandey, Preeti; Cabot, Peter J; Wallwork, Benjamin; Panizza, Benedict J; Parekh, Harendra S

2017-01-01

Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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Luis Marrero

2014-10-01

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

Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Science.gov (United States)

Marriott, James J; Miyasaki, Janis M; Gronseth, Gary; O'Connor, Paul W

2010-05-04

The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a "black box" warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in approximately 12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in approximately 0.4%, and leukemia occurs in approximately 0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking.

Greater happiness for a greater number: Is that possible in Austria?

NARCIS (Netherlands)

R. Veenhoven (Ruut)

2011-01-01

textabstractWhat is the final goal of public policy? Jeremy Bentham (1789) would say: greater happiness for a greater number. He thought of happiness as subjective enjoyment of life; in his words as “the sum of pleasures and pains”. In his time the happiness of the great number could not be measured

Greater happiness for a greater number: Is that possible in Germany?

NARCIS (Netherlands)

R. Veenhoven (Ruut)

2009-01-01

textabstractWhat is the final goal of public policy? Jeremy Bentham (1789) would say: greater happiness for a greater number. He thought of happiness as subjective enjoyment of life; in his words as “the sum of pleasures and pains”. In his time the Happiness of the great number could not be measured

Safety and efficacy of generic drugs with respect to brand formulation.

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Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

2013-12-01

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders.

Science.gov (United States)

Barajaz, Ashley M; Kliethermes, Christopher L

2017-12-01

Rodent models of Alcohol Use Disorders (AUD) are used extensively by preclinical researchers to develop new therapeutics for the treatment of AUD. Although these models play an important role in the development of novel, targeted therapeutics, their role in bringing therapeutics to clinical trials is unclear, as off-label use of existing medications not approved for the treatment of AUD is commonly seen in the clinic and clinical trials. In the current study, we used the Clinicaltrials.gov database to obtain a list of drugs that have been tested for efficacy in a clinical trial between 1997 and 2017. We then conducted a set of literature searches to determine which of the 98 unique drugs we identified had shown efficacy in a rodent model of an AUD prior to being tested in a clinical trial. We found that slightly less than half of the drugs tested in clinical trials (48%) had shown prior efficacy in any rodent model of an AUD, while the remaining 52% of drugs were used off-label, or in some cases, following non-published studies. This study raises the question of how clinical researchers incorporate results from preclinical studies in the decision to bring a drug to a clinical trial. Our results underscore the need for ongoing communication among preclinical and clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

Hubungan Antara Self-Efficacy Akademik dan Konsep Diri Akademik dengan Prestasi Akademik

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Lisa Ratriana Chairiyati

2013-10-01

Full Text Available This study discusses the relationship between academic self-efficacy and academic self-concept with academic achievement. The design of the study was descriptive - correlational, with a study sample of 192 children. Statistical Analysis with SPSS computer method (Statistical Package for Social Science version 17.0 for windows is used to find out characteristics of the respondents, and the regression analysis between the two independent variables (self-efficacy and academic self-concept academic and the dependent variable (academic achievement produce models regression . The results showed only variable Self-Efficacy (SE contributes positively to academic achievement. It is supported by the value of t-statistic greater than 1, 645 for the value . Hence it can be said that the dependent variable (academic achievement can be predicted with self-efficacy academic. 

Resilience Building in Students: The Role of Academic Self-Efficacy

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Cassidy, Simon

2015-01-01

Self-efficacy relates to an individual's perception of their capabilities. It has a clear self-evaluative dimension leading to high or low perceived self-efficacy. Individual differences in perceived self-efficacy have been shown to be better predictors of performance than previous achievement or ability and seem particularly important when individuals face adversity. The study investigated the nature of the association between academic self-efficacy (ASE) and academic resilience. Undergraduate student participants (N = 435) were exposed to an adverse situation case vignette describing either personal or vicarious academic adversity. ASE was measured pre-exposure and academic resilience was measured post-exposure. ASE was correlated with, and a significant predictor of, academic resilience and students exhibited greater academic resilience when responding to vicarious adversity compared to personal adversity. Identifying constructs that are related to resilience and establishing the precise nature of how such constructs influence academic resilience will assist the development of interventions aimed at promoting resilience in students. PMID:26640447

Resilience Building in Students: The Role of Academic Self-Efficacy

Directory of Open Access Journals (Sweden)

Simon eCassidy

2015-11-01

Full Text Available Self-efficacy relates to an individual’s perception of their capabilities. It has a clear self-evaluative dimension leading to high or low perceived self-efficacy. Individual differences in perceived self-efficacy have been shown to be better predictors of performance than previous achievement or ability and seem particularly important when individuals face adversity. The study investigated the nature of the association between academic self-efficacy (ASE academic resilience. Undergraduate student participants (N=435 were exposed to an adverse situation case vignette describing either personal or vicarious academic adversity. ASE was measured pre-exposure and academic resilience was measured post- exposure. ASE was correlated with, and a significant predictor of, academic resilience and students exhibited greater academic resilience when responding to vicarious adversity compared to personal adversity. Identifying constructs that are related to resilience and establishing the precise nature of how such constructs influence resilience will assist the development of interventions aimed at promoting resilience in students.

Parenting Efficacy and Support in Mothers With Dual Disorders in a Substance Abuse Treatment Program.

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Brown, Suzanne; Hicks, Laurel M; Tracy, Elizabeth M

2016-01-01

Approximately 73% of women entering treatment for substance use disorders are mothers of children younger than 18, and the high rate of mental health disorders among mothers with substance use disorders increases their vulnerability to poor parenting practices. Parenting efficacy and social support for parenting have emerged as significant predictors of positive parenting practices among families at risk for child maltreatment. The purpose of the current study was to examine the impact of parenting support and parenting efficacy on the likelihood of out-of-home placement and custody status among the children of mothers with dual substance use and mental health disorders. This study examined the impact of parenting efficacy and assistance with childcare on the likelihood of child out-of-home placement and custody status among 175 mothers with diagnosed dual substance and mental health disorder and in treatment for substance dependence. Logistic regression was utilized to assess the contributions of parenting efficacy and the number of individuals in mothers' social networks who assist with childcare to the likelihood of out-of-home placement and custody loss of children. Parenting efficacy was also examined as a mediator using bootstrapping in PROCESS for SPSS. Greater parenting efficacy was associated with lower likelihood of having at least one child in out-of-home placement (B = -.064, SE = .029, p = .027) and lower likelihood of loss of child custody (B = -.094, SE = .034, p = .006). Greater number of children in the 6 to 18 age range predicted greater likelihood of having at least one child in the custody of someone else (B = .409, SE = .171, p = .017) and in out-of-home placement (B = .651, SE = .167, p child in out-of-home placement (B = .927, SE = .382, p = .015) or to have lost custody of a child (B = -1.31, SE = .456, p = .004). Finally, parenting efficacy mediated the relationship between parenting support and likelihood of out-of-home placement (effect

[Efficacy and Safety Evaluation of Bushen Shuji Granule in Treating Ankylosing Spondylitis Patients: a Clinical Study].

Science.gov (United States)

Kong, Wei-ping; Tao, Qing-wen; Zhang, Ying-ze; Yang, Shu; Xu, Yuan; Zhu, Xiao-xia; Jin, Yue; Yang, Wen-xue; Yan, Xiao-ping

2015-06-01

To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients. A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment. After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy

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Quynh Nguyen

2017-10-01

Full Text Available Duchenne muscular dystrophy (DMD is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs is one of the most promising strategies. This strategy aims to restore the reading frame, thus producing a truncated, yet functioning dystrophin protein. In 2016, the Food and Drug Administration (FDA conditionally approved the first AO-based drug, eteplirsen (Exondys 51, developed for DMD exon 51 skipping. An accurate and reproducible method to quantify exon skipping efficacy is essential for evaluating the therapeutic potential of different AOs sequences. However, previous in vitro screening studies have been hampered by the limited proliferative capacity and insufficient amounts of dystrophin expressed by primary muscle cell lines that have been the main system used to evaluate AOs sequences. In this paper, we illustrate the challenges associated with primary muscle cell lines and describe a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies.

Does self-efficacy causally influence initial smoking cessation? An experimental study.

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Shadel, William G; Martino, Steven C; Setodji, Claude; Cervone, Daniel; Witkiewitz, Katie

2017-10-01

Self-efficacy has been associated with smoking cessation outcomes in many correlational research studies, but strong causal inferences are lacking. This study tested whether self-efficacy affects initial smoking cessation in a laboratory experiment, which will allow for stronger causal inferences in this domain of inquiry. Participants (n=103 motivated adult smokers) were provided with brief cessation treatment over three days in preparation for quitting on a target quit day (TQD). In addition, participants were randomized to one of two standard self-efficacy manipulations in the form of bogus feedback about their chances of quitting smoking. Participants in the Average Chances of Quitting (ACQ) condition took a computerized test and were told (falsely) that the test showed that they had the same chances of quitting as everyone else in the study. Participants in the High Chances of Quitting (HCQ) condition took the same computerized test and were told (falsely) that the test showed that they had a greater chance of quitting compared to everyone else in the study. The main outcome was whether participants were able to quit for 24h on the TQD. Results revealed that HCQ participants had a significantly greater chance of quitting smoking compared to ACQ participants. However, these effects were not attributable to changes in self-efficacy brought about by the manipulation. An exploration of other potential mediators showed that the manipulation actually influenced smoking outcome expectancies, and changes in these outcome expectancies influenced initial smoking cessation. The results highlight the conceptual and empirical challenges with manipulating self-efficacy in the smoking literature. Copyright © 2017. Published by Elsevier Ltd.

Liver cell-targeted delivery of therapeutic molecules.

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Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Approaches to Preventative and Therapeutic HIV vaccines

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Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

2016-01-01

Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

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Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Reducing therapeutic misconception: A randomized intervention trial in hypothetical clinical trials.

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Paul P Christopher

Full Text Available Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials.This prospective randomized trial was conducted from 2015 to 2016 to test the efficacy of an informed consent intervention based on scientific reframing compared to a traditional informed consent procedure (control in reducing therapeutic misconception among patients considering enrollment in hypothetical clinical trials modeled on real-world studies for one of five disease categories. Patients with diabetes mellitus, hypertension, coronary artery disease, head/neck cancer, breast cancer, and major depression were recruited from medical clinics and a clinical research volunteer database. The primary outcomes were therapeutic misconception, as measured by a validated, ten-item Therapeutic Misconception Scale (range = 10-50, and willingness to participate in the clinical trial.154 participants completed the study (age range, 23-87 years; 92.3% white, 56.5% female; 74 (48.1% had been randomized to receive the experimental intervention. Therapeutic misconception was significantly lower (p = 0.004 in the scientific reframing group (26.4, 95% CI [23.7 to 29.1] compared to the control group (30.9, 95% CI [28.4 to 33.5], and remained so after controlling for education (p = 0.017. Willingness to participate in the hypothetical trial was not significantly different (p = 0.603 between intervention (52.1%, 95% CI [40.2% to 62.4%] and control (56.3%, 95% CI [45.3% to 66.6%] groups.An enhanced educational intervention augmenting

The mediational role of panic self-efficacy in cognitive behavioral therapy for panic disorder: A systematic review and meta-analysis

DEFF Research Database (Denmark)

Fentz, Hanne Nørr; Arendt, Mikkel; OToole, Mia Skytte

2014-01-01

Cognitive models of panic disorder (PD) with and without agoraphobia have stressed the role of catastrophic beliefs of bodily symptoms as a central mediating variable of the efficacy of cognitive behavioral therapy (CBT). Perceived ability to cope with or control panic attacks, panic self......-efficacy, has also been proposed to play a key role in therapeutic change; however, this cognitive factor has received much less attention in research. The aim of the present review is to evaluate panic self-efficacy as a mediator of outcome in CBT for PD using descriptive and meta-analytic procedures. We...... an association between change in panic self-efficacy and change in outcome during therapy (criterion 2); three tested, and one established formal statistical mediation of panic self-efficacy (criterion 3); while four tested and three found change in panic self-efficacy occurring before the reduction of panic...

Fermented dairy productsin children’ diet: Preventive and therapeutic possibilities of their use

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M. K. Bekhtereva

2017-01-01

Full Text Available The article analyzes the preventive and therapeutic possibilities of using probiotic fermented dairy products (baby curds, yoghurts, biolacts in children with various pathological conditions. It outlines their effect in preventing respiratory and intestinal infections in children of different ages. Incorporation of probiotic strains with proven efficacy (including those as probiotic fermented dairy products into the combination treatment of pathological conditions associated with Helicobacter pylori is shown to significantly increase the efficiency of eradication therapy and to prevent the development antibiotic-associated diarrhea.

Effect of Therapeutic Touch in Patients with Cancer: a Literature Review.

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Tabatabaee, Amir; Tafreshi, Mansoureh Zagheri; Rassouli, Maryam; Aledavood, Seyed Amir; AlaviMajd, Hamid; Farahmand, Seyed Kazem

2016-04-01

The use of complementary and alternative medicine (CAM) techniques has been growing. The National Center for Complementary and Alternative Medicine places therapeutic touch (TT) into the category of bio field energy. This literature review is aimed at critically evaluating the data from clinical trials examining the clinical efficacy of therapeutic touch as a supportive care modality in adult patients with cancer. Electronic databases (PubMed, Scopus, Scholar Google, and Science Direct) were searched from the year 1990 to 2015 to locate potentially relevant peer-reviewed articles using the key words therapeutic touch, touch therapy, neoplasm, cancer, and CAM. Additionally, relevant journals and references of all the located articles were manually searched for other potentially relevant studies. The number of 334 articles was found on the basis of the key words, of which 17 articles related to the clinical trial were examined in accordance with the objectives of the study. A total of 6 articles were in the final dataset in which several examples of the positive effects of healing touch on pain, nausea, anxiety and fatigue, and life quality and also on biochemical parameters were observed. Based on the results of this study, an affirmation can be made regarding the use of TT, as a non-invasive intervention for improving the health status in patients with cancer. Moreover, therapeutic touch was proved to be a useful strategy for adult patients with cancer.

Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma

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Bag?, Juli R.; Alfonso-Pecchio, Adolfo; Okolie, Onyi; Dumitru, Raluca; Rinkenbaugh, Amanda; Baldwin, Albert S.; Miller, C. Ryan; Magness, Scott T.; Hingtgen, Shawn D.

2016-01-01

Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced ap...

The Relationship between Career Decision-Making Self-Efficacy and Vocational Outcome Expectations of Preservice Special Education Teachers

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Baglama, Basak; Uzunboylu, Huseyin

2017-01-01

Social cognitive career theory, which is one of the most studied career approaches, recently proposed that self-efficacy and outcome expectations are important determinants of the career choice process. Career self-efficacy and vocational outcome expectations might both result in avoiding or having greater motivation levels in terms of career…

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

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Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Medication adherence in schizophrenia: The role of insight, therapeutic alliance and perceived trauma associated with psychiatric care.

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Tessier, Arnaud; Boyer, Laurent; Husky, Mathilde; Baylé, Franck; Llorca, Pierre-Michel; Misdrahi, David

2017-11-01

Medication non adherence in schizophrenia is a major cause of relapse and hospitalization and remains for clinicians an important challenge. This study investigates the associations between insight, therapeutic alliance, perceived trauma related to psychiatric treatment and medication adherence in patients with schizophrenia. In this multicenter study, 72 patients were assessed regarding symptomatology, self-reported adherence with medication, insight, medication side-effects, therapeutic alliance and perceived trauma related to psychiatric treatment. Structural Equation Modeling (SEM) was used to test predicted paths among these variables. The data fit a model in which medication adherence was directly predicted by insight, therapeutic alliance and perceived trauma related to psychiatric treatment. Perceived trauma moderates the role of insight on medication adherence. The final model showed good fit, based on four reliable indices. Greater adherence was correlated with higher insight, higher therapeutic alliance and lower perceived trauma. These three variables appear to be important determinants of patient's medication adherence. Medication adherence could be enhanced by reducing perceived trauma and by increasing insight. The need for mental health providers to acknowledge patients' potentially traumatic experience with psychiatric treatment and the need to encourage greater involvement in care are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Mental Health Disorder Therapeutic Modalities Modified for the GMS.

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Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-12-01

Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. The finding of this review confirms the

Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction.

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Meephansan, Jitlada; Thummakriengkrai, J; Ponnikorn, S; Yingmema, W; Deenonpoe, R; Suchonwanit, P

2017-11-01

Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.

FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study

DEFF Research Database (Denmark)

Geva, Ravit; Vecchione, Loredana; Kalogeras, Konstantinos T

2015-01-01

OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. DESIGN: To show a HR advantage ...

Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabis.

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Brunt, Tibor M; van Genugten, Marianne; Höner-Snoeken, Kathrin; van de Velde, Marco J; Niesink, Raymond J M

2014-06-01

In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.

Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles

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Bin Zhang

2016-02-01

Full Text Available The intense research focus on stem and progenitor cells could be attributed to their differentiation potential to generate new cells to replace diseased or lost cells in many highly intractable degenerative diseases, such as Alzheimer disease, multiple sclerosis, and heart diseases. However, experimental and clinical studies have increasingly attributed the therapeutic efficacy of these cells to their secretion. While stem and progenitor cells secreted many therapeutic molecules, none of these molecules singly or in combination could recapitulate the functional effects of stem cell transplantations. Recently, it was reported that extracellular vesicles (EVs could recapitulate the therapeutic effects of stem cell transplantation. Based on the observations reported thus far, the prevailing hypothesis is that stem cell EVs exert their therapeutic effects by transferring biologically active molecules such as proteins, lipids, mRNA, and microRNA from the stem cells to injured or diseased cells. In this respect, stem cell EVs are similar to EVs from other cell types. They are both primarily vehicles for intercellular communication. Therefore, the differentiating factor is likely due to the composition of their cargo. The cargo of EVs from different cell types are known to include a common set of proteins and also proteins that reflect the cell source of the EVs and the physiological or pathological state of the cell source. Hence, elucidation of the stem cell EV cargo would provide an insight into the multiple physiological or biochemical changes necessary to affect the many reported stem cell-based therapeutic outcomes in a variety of experimental models and clinical trials.

Percutaneous transhepatic biliary metal stent for malignant hilar obstruction: results and predictive factors for efficacy in 159 patients from a single center.

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Li, Mingwu; Bai, Ming; Qi, Xingshun; Li, Kai; Yin, Zhanxin; Wang, Jianhong; Wu, Wenbing; Zhen, Luanluan; He, Chuangye; Fan, Daiming; Zhang, Zhuoli; Han, Guohong

2015-06-01

To investigate and compare the efficacy and safety of percutaneous transhepatic biliary stenting (PTBS) using a one- or two-stage procedure and determine the predictive factors for the efficacious treatment of malignant hilar obstruction (MHO). 159 consecutive patients with MHO who underwent PTBS were enrolled between January 2010 and June 2013. Patients were classified into one- or two-stage groups. Independent predictors of therapeutic success were evaluated using a logistic regression model. 108 patients were treated with one-stage PTBS and 51 patients were treated with two-stage PTBS. The stents were technically successful in all patients. Successful drainage was achieved in 114 patients (71.4 %). A total of 42 early major complications were observed. Re-interventions were attempted in 23 patients during follow-up. The cumulative primary patency rates at 3, 6, and 12 months were 88, 71, and 48 %, respectively. Stent placement using a one- or two-stage procedure did not significantly affect therapeutic success, early major complications, median stent patency, or survival. A stent placed across the duodenal papilla was an independent predictor of therapeutic success (odds ratio = 0.262, 95 % confidence interval [0.107-0.642]). Patients with stents across papilla had a lower rate of cholangitis compared with patients who had a stent above papilla (7.1 vs. 20.3 %, respectively, p = 0.03). The majority of patients with MHO who underwent one-stage PTBS showed similar efficacy and safety outcomes compared with those who underwent two-stage PTBS. Stent placement across the duodenal papilla was associated with a higher therapeutic success rate.

Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

Science.gov (United States)

2014-01-01

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

Self-efficacy and enjoyment of middle school children performing the progressive aerobic cardiovascular endurance run (PACER).

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Kane, Irene; Robertson, Robert J; Fertman, Carl I; Nagle, Elizabeth F; McConnaha, Wendell R; Rabin, Bruce S

2013-10-01

Self-efficacy and enjoyment were examined among 34 middle school children (M age = 12.5 yr.) performing the Progressive Aerobic Cardiovascular Endurance Run (PACER). Exercise self-efficacy (running) and physical activity enjoyment were measured after viewing a video illustrating the PACER, and subsequently following a PACER test. Significantly greater pre- than post-exercise self-efficacy was reported; enjoyment scores did not differ. Ratings of self-efficacy were higher before exercise than after, but enjoyment scores were not significantly different. A significant correlation was found between post-exercise self-efficacy and enjoyment, but not between pre-exercise self-efficacy and enjoyment. Although positive correlations were found between PACER laps and pre-/post-exercise self-efficacy, correlations with ratings of enjoyment were not significant. Exercise self-efficacy was associated with children's beliefs about the task-specific PACER aerobic exercise; however, exercise enjoyment was stable. Children's self-efficacy and enjoyment beliefs should be considered when developing interventional strategies to promote aerobic exercise participation.

Impact of language anxiety and self-efficacy on accessing Internet sites.

Science.gov (United States)

Yang, Hui-Jen; Lay, Yun-Long; Tsao, Wen-Yu; Liou, Yi-Chin; Lin, Cheng-Kun

2007-04-01

Language interface plays a critical role as the foundation of communication. Possessing greater fluency in the host language can lead to increased opportunities for interaction with host members. This research is to examine the impact of language and Internet usage anxiety and self-efficacy on the intended uses of Internet sites, respectively. By the same token, whether Internet/language self-efficacy would mediate the effects of Internet/language anxiety on the intention of the Internet site use is also examined. A valid sample of 368 undergraduates was tested in this study. The path analysis results mostly supported the model tested. The results display that the anxiety of language and Internet use have significantly influenced self-efficacy of Internet use and language, respectively. Anxiety about language and Internet use have also significantly influenced the intention to use Internet sites individually. Furthermore, language self-efficacy has significantly influenced the intention to use Internet sites, but Internet self-efficacy has not. The implications are discussed at the end of the paper.

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Jiang Li

2017-01-01

Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

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