The Course of Self-Efficacy for Therapeutic Use of Self in Norwegian Occupational Therapy Students: A 10-Month Follow-Up Study

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Kathrin Schwank

2018-01-01

Full Text Available Background. Occupational therapy students need to develop self-efficacy for managing the therapeutic relationship in practice. This study examined the 10-month trajectories of Norwegian students’ self-efficacy for use of self. Methods. Eighty-nine students completed self-efficacy questionnaires related to the use of self after a workshop and at 3- and 10-month follow-up. Changes on the three outcome measures (self-efficacy for therapeutic mode use, for recognizing clients’ interpersonal characteristics, and for managing interpersonal events were analyzed with repeated measures ANOVA. Results. Across the follow-up period, the students improved their self-efficacy for therapeutic mode use (partial η2 = 0.44, p<0.001, for recognizing clients’ interpersonal characteristics (partial η2 = 0.81, p<0.001, and for managing interpersonal events (partial η2=0.32, p<0.001. Conclusion. The increased self-efficacy for use of self that was found at 3-month follow-up was maintained at 10-month follow-up. The results indicate that students may experience a boost in self-efficacy for therapeutic use of self after a brief workshop and that these changes can be sustained over time.

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.

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.

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.

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

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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

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.

TESTING ANTIMICROBIAL EFFICACY ON POROUS MATERIALS

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The efficacy of antimicrobial treatments to eliminate or control biological growth in the indoor environment can easily be tested on nonporous surfaces. However, the testing of antimicrobial efficacy on porous surfaces, such as those found in the indoor environment [i.e., gypsum ...

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)

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.

Therapeutic orientations, professional efficacy, and burnout among substance abuse social workers in Israel.

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Tartakovsky, Eugene; Kovardinsky, Slava

2013-07-01

This study investigates the therapeutic orientations of substance abuse social workers and the relationship between these orientations and burnout. Ninety-two social workers who provided outpatient treatment to people suffering from substance-related disorders in Israel participated in the study. The results obtained demonstrated that the substance abuse social workers adhere more to the psychodynamic and ecosystemic therapeutic orientations than to the cognitive-behavioral orientation. A greater adherence to the cognitive-behavioral orientation was associated with a higher sense of professional efficacy; a greater adherence to the psychodynamic orientation was associated with a higher level of exhaustion; and greater adherence to the ecosystemic orientation was associated with lower levels of exhaustion and cynicism. Female social workers reported lower levels of exhaustion and cynicism. The cognitive-behavioral orientation mediated the connection between the social workers' experience in the field of substance abuse and two dimensions of burnout-exhaustion and professional efficacy. Significance of the findings for improving the well-being of substance abuse social workers and for the advancement of psychosocial services is discussed. Copyright © 2013 Elsevier Inc. 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

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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.

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.

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

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

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Sayeda Yasmin-Karim

2018-04-01

Full Text Available Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs, with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

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....

An Objective Approach for Burkholderia pseudomallei Strain Selection as Challenge Material for Medical Countermeasures Efficacy Testing

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Van Zandt, Kristopher E.; Tuanyok, Apichai; Keim, Paul S.; Warren, Richard L.; Gelhaus, H. Carl

2012-01-01

Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs), the high mortality rate...

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

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

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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.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Design of clinical trials for therapeutic cancer vaccines development.

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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.

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)

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

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Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

2018-06-01

Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

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

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

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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 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

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.

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.

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.

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.

An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing

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Kristopher E. Van Zandt

2012-09-01

Full Text Available Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs, the high mortality rates associated with melioidosis raises significant ethical issues concerning treating individuals with new compounds with unknown efficacies. The US Food and Drug Administration (FDA has formulated a set of guidelines for the licensure of new MCMs to treat diseases in which it would be unethical to test the efficacy of these drugs in humans. The FDA Animal Rule 21 CFR 314 calls for consistent, well-characterized B. pseudomallei strains to be used as challenge material in animal models. In order to facilitate the efficacy testing of new MCMs for melioidosis using animal models, we intend to develop a well-characterized panel of strains for use. This panel will comprise of strains that were isolated from human cases, have a low passage history, are virulent in animal models, and are well characterized phenotypically and genotypically. We have reviewed published and unpublished data on various B. pseudomallei strains to establish an objective method for selecting the strains to be included in the panel of B. pseudomallei strains with attention to five categories: animal infection models, genetic characterization, clinical and passage history, and availability of the strain to the research community. We identified 109 strains with data in at least one of the five categories, scored each strain based on the gathered data and identified 6 strains as candidate for a B. pseudomallei strain panel.

An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing.

Science.gov (United States)

Van Zandt, Kristopher E; Tuanyok, Apichai; Keim, Paul S; Warren, Richard L; Gelhaus, H Carl

2012-01-01

Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs), the high mortality rates associated with melioidosis raises significant ethical issues concerning treating individuals with new compounds with unknown efficacies. The US Food and Drug Administration (FDA) has formulated a set of guidelines for the licensure of new MCMs to treat diseases in which it would be unethical to test the efficacy of these drugs in humans. The FDA "Animal Rule" 21 CFR 314 calls for consistent, well-characterized B. pseudomallei strains to be used as challenge material in animal models. In order to facilitate the efficacy testing of new MCMs for melioidosis using animal models, we intend to develop a well-characterized panel of strains for use. This panel will comprise of strains that were isolated from human cases, have a low passage history, are virulent in animal models, and are well-characterized phenotypically and genotypically. We have reviewed published and unpublished data on various B. pseudomallei strains to establish an objective method for selecting the strains to be included in the panel of B. pseudomallei strains with attention to five categories: animal infection models, genetic characterization, clinical and passage history, and availability of the strain to the research community. We identified 109 strains with data in at least one of the five categories, scored each strain based on the gathered data and identified six strains as candidate for a B. pseudomallei strain panel.

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.

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...

In vivo testing of the therapeutic efficacy of chloroquine on falciparum malaria infections in Chirundu, Mashonaland West, Zimbabwe.

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Barduagni, P; Schwartz, U; Nyamayaro, W; Chauke, T L

1998-10-01

To detect the level of the in vivo chloroquine efficacy in falciparum malaria infections, in order to assess the need for change in the management and treatment of uncomplicated malaria. Prospective descriptive study. Chirundu Rural Clinic, Mashonaland West Province. 63 patients confirmed by a positive blood slide for P. falciparum who attended Chirundu clinic, who were eligible for the study and, who also agreed to participate. Frequency of treatment success, early treatment failure and late treatment failure in uncomplicated patients treated with chloroquine. Out of 63 cases enrolled and completely followed up, chloroquine treatment was effective in 54 cases (85.7%) and was not effective in nine cases (14.3%). All treatment failures were successfully treated with sulphadoxine + pyrimethamine (Fansidar) or quinine following the approved guidelines. Chloroquine remains highly effective in the treatment of malaria due to P. falciparum in the Zambezi Valley of Hurungwe district and therefore, has to remain the first line drug. Likewise, guidelines for the use of sulphadoxine + pyrimethamine (Fansidar) or quinine as second line drugs, are adequate to the local situation. Health workers directly supervised the patients when they were swallowing the tablets during the whole course, and this without doubt, indirectly increased the efficacy of chloroquine. It is vital to confirm the malaria diagnosis on the spot appointing microscopists or distributing a limited stock of Parasight-F test.

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.

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.

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 of propylthiouracil in psoriasis: An open-label study

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Pushpa Gnanaraj

2011-01-01

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

In vitro efficacy of cold atmospheric pressure plasma on S. sanguinis biofilms in comparison of two test models

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Gorynia, Susanne

2013-04-01

Full Text Available [english] Dental plaque critically affects the etiology of caries, periodontitis and periimplantitis. The mechanical removal of plaque can only be performed partially due to limited accessibility. Therefore, plaque still represents one of the major therapeutic challenges. Even though antiseptic mouth rinses reduce the extent of biofilm temporarily, plaque removal remains incomplete and continuous usage can even result in side effects. Here we tested argon plasma produced by kinpen09 as one option to inactivate microorganisms and to eliminate plaque. biofilms cultivated in either the European Biofilm Reactor (EUREBI or in 24 well plates were treated with argon plasma. In both test systems a homogeneous, good analyzable and stable biofilm was produced on the surface of titan plates within 72 h (>6,9 log CFU/ml. Despite the significantly more powerful biofilm production in EUREBI, the difference of 0.4 log CFU/ml between EUREBI and the 24 well plates was practically not relevant. For that reason both test models were equally qualified for the analysis of efficacy of cold atmospheric pressure plasma. We demonstrate a significant reduction of the biofilm compared to the control in both test models. After plasma application of 180 s the biofilm produced in EUREBI or in 24 well plates was decreased by 0.6 log CFU/ml or 0.5 log CFU/ml, respectively. In comparison to recently published studies analyzing the efficacy of kinpen09, produces a hardly removable biofilm. Future investigations using reduced distances between plasma source and biofilm, various compositions of plasma and alternative plasma sources will contribute to further optimization of the efficacy against biofilms.

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.

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 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

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.

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.

Calibration of Self-Efficacy for Conducting a Chi-Squared Test of Independence

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Zimmerman, Whitney Alicia; Goins, Deborah D.

2015-01-01

Self-efficacy and knowledge, both concerning the chi-squared test of independence, were examined in education graduate students. Participants rated statements concerning self-efficacy and completed a related knowledge assessment. After completing a demographic survey, participants completed the self-efficacy and knowledge scales a second time.…

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.

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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.

HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine.

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Graziani, Gina M; Angel, Jonathan B

2016-07-01

Although current antiretroviral therapy (ART) has transformed HIV infection into a chronic, manageable disease, ART does not cure HIV infection. Furthermore, the majority of the world's infected individuals live in resource-limited countries in which access to ART is limited. Thus, the development of an effective therapeutic HIV vaccine would be an invaluable treatment alternative. Developed by the late Dr. Jonas Salk, HIV-1 Immunogen (Remune®) is a candidate therapeutic vaccine that has been studied in thousands of HIV-infected individuals in more than a dozen clinical trials during almost three decades. This Drug Evaluation, which summarizes the results of these trials that have shown the vaccine to be safe and immunogenic, also discusses the contradictory and controversial conclusions drawn from the phases 2, 2/3 and 3 trials that assessed the clinical efficacy of this vaccine. Given the lack of unequivocal clinical benefits of HIV-1 Immunogen despite almost 30 years of extensive testing, it does not appear, in our view, that this vaccine is a clinically effective immunotherapy. However, inclusion of this vaccine in the newly proposed 'Kick/Shock and Kill' strategy for HIV eradication, or use as a prophylactic vaccine, could be considered for future trials.

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

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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.

Recent Advances in Stem Cell-Based Therapeutics for Stroke

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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...

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

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

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

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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.

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

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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.

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

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.

Self-efficacy in rheumatoid arthritis: translation and test of validity, reliability and sensitivity of the Danish version of the Rheumatoid Arthritis Self-Efficacy Questionnaire (RASE)

DEFF Research Database (Denmark)

Primdahl, J; Wagner, L; Hørslev-Petersen, Kim

2010-01-01

To describe the translation and test of the Danish version of the original British 'Rheumatoid Arthritis Self-Efficacy Questionnaire' (RASE).......To describe the translation and test of the Danish version of the original British 'Rheumatoid Arthritis Self-Efficacy Questionnaire' (RASE)....

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

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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.

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.

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

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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.

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

Directory of Open Access Journals (Sweden)

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.

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 ...

Development and psychometric evaluation of an information literacy self-efficacy survey and an information literacy knowledge test.

Science.gov (United States)

Tepe, Rodger; Tepe, Chabha

2015-03-01

To develop and psychometrically evaluate an information literacy (IL) self-efficacy survey and an IL knowledge test. In this test-retest reliability study, a 25-item IL self-efficacy survey and a 50-item IL knowledge test were developed and administered to a convenience sample of 53 chiropractic students. Item analyses were performed on all questions. The IL self-efficacy survey demonstrated good reliability (test-retest correlation = 0.81) and good/very good internal consistency (mean κ = .56 and Cronbach's α = .92). A total of 25 questions with the best item analysis characteristics were chosen from the 50-item IL knowledge test, resulting in a 25-item IL knowledge test that demonstrated good reliability (test-retest correlation = 0.87), very good internal consistency (mean κ = .69, KR20 = 0.85), and good item discrimination (mean point-biserial = 0.48). This study resulted in the development of three instruments: a 25-item IL self-efficacy survey, a 50-item IL knowledge test, and a 25-item IL knowledge test. The information literacy self-efficacy survey and the 25-item version of the information literacy knowledge test have shown preliminary evidence of adequate reliability and validity to justify continuing study with these instruments.

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

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

Efficacy Testing of Pesticides used for Invertebrate Pests and Fire Ants

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Event page for the upcoming Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) meeting on Efficacy Testing of Pesticides used for Invertebrate Pests and Fire Ants

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.

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.

Quantitative sensory testing of neuropathic pain patients: potential mechanistic and therapeutic implications.

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Pfau, Doreen B; Geber, Christian; Birklein, Frank; Treede, Rolf-Detlef

2012-06-01

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

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.

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

Science.gov (United States)

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.

College students and HIV testing: cognitive, emotional self-efficacy, motivational and communication factors

Science.gov (United States)

Lin, Carolyn A.; Roy, Deya; Dam, Linda; Coman, Emil N.

2017-01-01

Most college students have never been tested for HIV, even though they regularly have unprotected sex and multiple sex partners. Theory-based research addressing factors influencing HIV testing among college students is limited. This study explored this topic via a conceptual framework that integrates the health belief model with emotion and communication factors. Data was collected with a sample of four focus group panels, including two male and two female groups (N = 52). Transcripts for the seven discussion questions were produced based on the audio recordings of group sessions. Two research assistants reviewed, summarized and cross-validated the discussion content to address each of the four research questions under study. Students believe HIV to be a severe health threat, but feel ‘invincible’ about contracting the virus. Their low emotional self-efficacy is a barrier for adopting HIV testing. Gaining social approval and emotional support for making a testing decision can help them overcome the perceived fear, stigma and lack of response efficacy associated with taking the test. Students are open to receiving cues to action via confidential HIV-testing related communication from health professionals or important others as well as media messaging from various sources. Bridging the perceptual-emotional gap between perceived invulnerability and fear can help increase emotional self-efficacy in coping with HIV testing. Normalizing HIV testing as a primary care routine for harm avoidance/reduction will increase perceived benefits of testing. Communicating cues to action will help reinforce HIV testing as a societally approved and socially supported protective behavioral norm. PMID:29399038

appraisal of the efficacy of tactile subjective test for anaesthesia of ...

African Journals Online (AJOL)

Dr Olaleye

efficacy. In conducting subjective test after inferior dental and lingual nerves block anaesthesia, the patient was often asked .... procedures. It should ... computerised injection system for local pain control. ... antecedents of dental anxiety. JADA ...

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

Science.gov (United States)

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.

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 ...

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

Science.gov (United States)

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.

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...

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

Directory of Open Access Journals (Sweden)

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.

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.

Effects of UGT1A9 genetic polymorphisms on monohydroxylated derivative of oxcarbazepine concentrations and oxcarbazepine monotherapeutic efficacy in Chinese patients with epilepsy.

Science.gov (United States)

Lu, Yao; Fang, Youxin; Wu, Xunyi; Ma, Chunlai; Wang, Yue; Xu, Lan

2017-03-01

The human UDP-glucuronosyltransferase which is genetically polymorphic catalyzes glucuronidations of various drugs. The interactions among UGT1A4, UGT1A6, UGT1A9, and UGT2B15 genetic polymorphisms, monohydroxylated derivative (MHD) of oxcarbazepine (OXC) plasma concentrations, and OXC monotherapeutic efficacy were explored in 124 Chinese patients with epilepsy receiving OXC monotherapy. MHD is the major active metabolite of OXC, and its plasma concentration was measured using high-performance liquid chromatography when patients reached their maintenance dose of OXC. Genomic DNA was extracted from whole blood and SNP genotyping performed using PCR followed by dideoxy chain termination sequencing. We followed the patients for at least 1 year to evaluate the OXC monotherapy efficacy. Patients were divided into two groups according to their therapeutic outcome: group 1, seizure free; group 2, not seizure free. The data were analyzed using T test, one-way analysis of variance (ANOVA), Kruskal-Wallis test, chi-square test, Fisher's exact test, correlation analysis, and multivariate regression analysis. T test analysis showed that MHD plasma concentrations were significantly different between the two groups (p = 0.002). One-way ANOVA followed by Bonferroni post hoc testing of four candidate SNPs revealed that carriers of the UGT1A9 variant allele I399 C > T (TT 13.28 ± 7.44 mg/L, TC 16.41 ± 6.53 mg/L) had significantly lower MHD plasma concentrations and poorer seizure control than noncarriers (CC 22.24 ± 8.49 mg/L, p effects of UGT1A9 genetic polymorphisms on MHD plasma concentrations and OXC therapeutic efficacy. Through MHD monitoring, we can predict OXC therapeutic efficacy, which may be useful for the personalization of OXC therapy in epileptic patients.

Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.

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Robert A Harrison

2017-10-01

Full Text Available Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa.We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom.None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro

Testing the Self-Efficacy-Performance Linkage of Social-Cognitive Theory.

Science.gov (United States)

Harrison, Allison W.; Rainer, R. Kelly, Jr.; Hochwarter, Wayne A.; Thompson, Kenneth R.

1997-01-01

Briefly reviews Albert Bandura's Self-Efficacy Performance Model (ability to perform a task is influenced by an individual's belief in their capability). Tests this model with a sample of 776 university employees and computer-related knowledge and skills. Results supported Bandura's thesis. Includes statistical tables and a discussion of related…

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

Directory of Open Access Journals (Sweden)

Thomas L. Chenevert

2002-10-01

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

Understanding music’s therapeutic efficacy: Implications for music education

Directory of Open Access Journals (Sweden)

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.

The Online Big Blue Test for Promoting Exercise: Health, Self-Efficacy, and Social Support.

Science.gov (United States)

Gómez-Zúñiga, Beni; Pousada, Modesta; Hernandez, Manny M; Colberg, Sheri; Gabarrón, Elia; Armayones, Manuel

2015-10-01

Recent articles have documented the influence of self-efficacy and social support on exercising. Simultaneously, insulin use is also related to the perception of self-efficacy and social support in patients with diabetes. We combine these two ideas through the Big Blue Test experience in a social networking site and propose to analyze whether a change in blood sugar levels after completion of the Big Blue Test and insulin use are related to the perception of self-efficacy and social support in patients with diabetes. To undergo the Big Blue Test, 3,926 participants voluntarily joined the Diabetes Hands Foundation. Responses were analyzed using descriptive analysis. The participants who reduced their blood glucose after exercise the least were those with lower self-efficacy and also with lower perceived social support. There seems to have been no relationship between changes in blood sugar level and the explicit intention of doing exercise in the future. Insulin-dependent participants demonstrated a lower perception of self-efficacy and social support than non-insulin-dependent participants. Change in blood glucose level or being insulin-dependent or not do not explain completely a health behavior such as exercise. Hence, self-efficacy and social support have an impact on behavioral change such as exercise to become a habit in people with diabetes, and this experience through a social networking site is an important tool for this behavioral change. For exercise to become a habit in people with diabetes, it is necessary to consider not only the crucial physiological variables, but also those psychological variables that clearly have an impact on behavioral change.

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

Science.gov (United States)

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

2010-05-01

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

Psychedelics and hypnosis: Commonalities and therapeutic implications.

Science.gov (United States)

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 monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

Science.gov (United States)

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.

TESTING ANTIMICROBIAL CLEANER EFFICACY ON GYPSUM WALLBOARD CONTAMINATED WITH STACHYBOTRYS CHARTARUM

Science.gov (United States)

Reducing occupant exposure to indoor mold growth is the goal of this research, through the efficacy testing of antimicrobial cleaners. Often mold contaminated building materials are not properly removed, but instead surface cleaners are applied in an attempt to alleviate the prob...

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)

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

Energy Technology Data Exchange (ETDEWEB)

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 ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system.

Science.gov (United States)

Tsuruta, James K; Dayton, Paul A; Gallippi, Caterina M; O'Rand, Michael G; Streicker, Michael A; Gessner, Ryan C; Gregory, Thomas S; Silva, Erick J R; Hamil, Katherine G; Moser, Glenda J; Sokal, David C

2012-01-30

Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive. Sprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment. We found that 3 MHz ultrasound delivered with 2.2 Watt per square cm power for fifteen minutes was necessary to deplete spermatocytes and spermatids from the testis and that this treatment significantly reduced epididymal sperm reserves. 3 MHz ultrasound treatment reduced total epididymal sperm count 10-fold lower than the wet-heat control and decreased motile sperm counts 1,000-fold lower than wet-heat alone. The current treatment regimen provided nominally more energy to the treatment chamber than Fahim's originally reported conditions of 1 MHz ultrasound delivered at 1 Watt per square cm for ten minutes. However, the true spatial average intensity, effective radiating area and power output of the transducers used by Fahim were not reported, making a direct comparison impossible. We found that germ cell depletion was most uniform and effective when we rotated the therapeutic transducer to mitigate non-uniformity of the beam field. The lowest sperm count was achieved when the coupling medium (3% saline) was held at 37 degrees C and two consecutive 15-minute treatments of 3 MHz ultrasound at 2.2 Watt per square cm were separated by 2 days. The non-invasive nature of ultrasound and its efficacy in reducing sperm count make therapeutic ultrasound a promising candidate for a male contraceptive. However, further studies must be conducted to confirm its efficacy in providing a contraceptive effect, to test the result of repeated use, to verify that the contraceptive effect is

TESTING ANTIMICROBIAL PAINT EFFICACY ON GYPSUM WALLBOARD CONTAMINATED WITH STACHYBOTRYS CHARTARUM

Science.gov (United States)

Often mold contaminated building materials are not properly removed, some surface cleaning is performed and paint is applied in an attempt to alleviate the problem. The efficacy of antimicrobial paints to eliminate or control mold regrowth on surfaces can easily be tested on non-...

Gestational diabetes mellitus in Greenland: a national study of prevalence and testing efficacy

Directory of Open Access Journals (Sweden)

Michael Lynge Pedersen

2016-08-01

Full Text Available Background: Within the last 20 years, the prevalence of gestational diabetes mellitus (GDM has been reported to be increasing worldwide in correlation with ethnic and geographic variations. The actual prevalence of GDM throughout all of Greenland remains unknown. Objective: The aim of this study was to estimate the prevalence of GDM among Greenlanders and non-Greenlanders living in Greenland and to estimate the efficacy of testing for GDM. Design: This study was performed as an observational, cross-sectional study including all women with permanent address in Greenland who had given birth to a singleton during 2014. The prevalence of GDM was calculated as the proportion of all pregnant women tested with a 75-g 2-h glucose tolerance test who had a 2-h capillary whole-blood glucose value of 8.5 mmol/l or above. Testing efficacy was calculated as the proportion of women who fulfilled the testing criteria who were actually tested in Greenland in 2014. Results: A total of 794 women (727 Greenlanders and 67 non-Greenlanders were included in the study. The prevalence of GDM among tested women was 3.3% (confidence interval, CI: 0.9–5.6 among Greenlanders and 12.5% (CI: 0–25.7 among non-Greenlanders, corresponding, respectively, to 1.0% (CI: 0.3–1.3 and 4.5% (CI: 0–9.4 of all singleton pregnancies in Greenland in 2014. The overall testing efficacy was 69.0% among all eligible residents of Greenland and 85.1% among eligible residents in the capital city, Nuuk. Conclusion: In conclusion, the prevalence of GDM seems quite low in Greenland. Although diagnostic testing activity has improved within the last 6 years, still around one-third of all pregnant women in all Greenland fulfilling the testing criteria were not tested. Universal testing for GDM may be needed to improve testing of GDM in Greenland.

Superantigen-Induced Cytokine Release from Whole-Blood Cell Culture as a Functional Measure of Drug Efficacy after Oral Dosing in Nonhuman Primates

National Research Council Canada - National Science Library

Krakauer, Teresa; Stephens, Julie; Buckley, Marilyn; Tate, Mallory

2007-01-01

...) closely resemble humans. We examined the ex vivo cytokine response of superantigen-stimulated whole-blood cells as a first step to therapeutic efficacy testing for bacterial superantigen-induced shock in NHP after oral dosing of pentoxifylline...

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; ...

The effect of time-management training on test-anxiety and self-efficacy of Iranian intermediate EFL learners

Directory of Open Access Journals (Sweden)

Biook Behnam

2014-01-01

Full Text Available The present study aimed to examine the effect of time-management training on Iranian EFL learners' test-anxiety and self-efficacy. A quasi-experimental design was used. The study was carried out in Tabriz Azad University and University of Applied Sciences and Technology. Thirty-eight BA students majoring in TEFL who enrolled in the above mentioned context in the academic year 1390-1391 participated in the study. The instruments used in the study were Time-Management Behavior Scale constructed by Macan, Shahani, Dipboye, et al. (1990, General Self-Efficacy Scale constructed by Jerusalem and Schwarzer (1992 and Westside Test-Anxiety Scale constructed by Driscoll (2007.The results indicated that there was a significant difference between the mean scores of experimental group's test-anxiety before and after time-management training and also there was a significant difference between the mean scores of experimental group and control group's test-anxiety after intervention. These findings also apply to the mean scores of self-efficacy. Therefore, it can be concluded that time-management training affects EFL learners' test-anxiety and self-efficacy. The findings of this study have some implications for researchers, teachers, universities and institutions.

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 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

Hidden consequences of political efficacy: Testing an efficacy-apathy model of political mobilization.

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Osborne, Danny; Yogeeswaran, Kumar; Sibley, Chris G

2015-10-01

Political efficacy-the belief that one can influence politics-is a key predictor of people's involvement in social movements. Political institutions that are open to change should, however, be seen as just. Thus, political efficacy may ironically undermine minority group members' support for collective action by simultaneously increasing their belief in the fairness of the system. The current study aims to examine this possibility in a national sample of Māori-New Zealand's indigenous minority population. Participants (N = 399) were Māori (Mage = 44.22; SD = 13.30) women (n = 272) and men (n = 115; unreported = 12) who completed a survey assessing their levels of (a) political efficacy, (b) system justification, and (c) support for the political mobilization of their group, as well as relevant demographic covariates. Consistent with past research, political efficacy had a positive direct effect on participants' support for the political mobilization of Māori. Nevertheless, political efficacy also had a negative indirect effect on political mobilization support via increases in system justification. These results held after controlling for participants' ethnic identification, self-efficacy, and conservatism. Our findings uncover a hidden consequence of political efficacy and show that, while believing that the political system is receptive to change predicts political mobilization, it can also undermine minorities' support for the mobilization of their group. Thus, our results uncover a previously unknown process that maintains inequality between ethnic minority and majority group members. (c) 2015 APA, all rights reserved).

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 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

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

Efficacy and safety of anthelmintics tested against Taenia solium cysticercosis in pigs.

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Ernatus Martin Mkupasi

Full Text Available Porcine cysticercosis, an infection caused by Taenia solium metacestodes, is continuously being reported in low-income countries of Latin America, Asia, and sub-Saharan Africa. The disease was declared eradicable by the International Task Force for Diseases Eradication (ITFDE in 1993, and it is listed among the 17 WHO Neglected Tropical Diseases and Neglected Zoonoses that are potentially eradicable. In view of that, WHO has proposed a step-wise approach to its elimination, including chemotherapy of infected pigs. Different drugs have been tested on porcine cysticercosis with varying efficacies. These include flubendazole, fenbendazole, albendazole, albendazole sulphoxide, oxfendazole, praziquantel, and nitazoxanide. This review summarises available information on the efficacies and adverse effects shown by these drugs in pigs. Oxfendazole has shown to be effective for the control of porcine cysticercosis; however, it needs to be integrated with other control approaches. There is a need for standardised guidelines for evaluating the efficacy of anthelmintics against porcine cysticercosis, and more efficacy studies are needed since the conclusions so far are based on a limited number of studies using few infected pigs.

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

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Anne Kleijn

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

Diagnostic efficacy of in vitro methods vs. skin testing in patients with inhalant allergies

International Nuclear Information System (INIS)

Corey, J.P.; Liudahl, J.J.; Young, S.A.; Rodman, S.M.

1991-01-01

The purpose of our study was to investigate the diagnostic efficacy of two selected methods of in vitro allergy testing. Specifically, the PRIST/modified RAST I125 isotope systems and the Quantizyme/modified EAST alkaline phosphatase method were compared. The time, expense, convenience, and diagnostic efficacy of the two procedures are discussed. Special attention is given to the practicality of each method for the practicing physician

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.

The development and psychometric testing of a Disaster Response Self-Efficacy Scale among undergraduate nursing students.

Science.gov (United States)

Li, Hong-Yan; Bi, Rui-Xue; Zhong, Qing-Ling

2017-12-01

Disaster nurse education has received increasing importance in China. Knowing the abilities of disaster response in undergraduate nursing students is beneficial to promote teaching and learning. However, there are few valid and reliable tools that measure the abilities of disaster response in undergraduate nursing students. To develop a self-report scale of self-efficacy in disaster response for Chinese undergraduate nursing students and test its psychometric properties. Nursing students (N=318) from two medical colleges were chosen by purposive sampling. The Disaster Response Self-Efficacy Scale (DRSES) was developed and psychometrically tested. Reliability and content validity were studied. Construct validity was tested by exploratory and confirmatory factor analysis. Reliability was tested by internal consistency and test-retest reliability. The DRSES consisted of 3 factors and 19 items with a 5-point rating. The content validity was 0.91, Cronbach's alpha coefficient was 0.912, and the intraclass correlation coefficient for test-retest reliability was 0.953. The construct validity was good (χ 2 /df=2.440, RMSEA=0.068, NFI=0.907, CFI=0.942, IFI=0.430, pself-efficacy in disaster response for Chinese undergraduate nursing students. Copyright © 2017. Published by Elsevier Ltd.

One More Reason to Learn a New Language: Testing Academic Self-Efficacy Transfer at Junior High School

Science.gov (United States)

Fryer, Luke K.; Oga-Baldwin, W. L. Quint

2017-01-01

Self-efficacy is an essential source of motivation for learning. While considerable research has theorised and examined the how and why of self-efficacy in a single domain of study, longitudinal research has not yet tested how self-efficacy might generalise or transfer between subjects such as mathematics, native and foreign language studies. The…

Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators

DEFF Research Database (Denmark)

Bänsch, Dietmar; Bonnemeier, Hendrik; Brandt, Johan

2015-01-01

AIMS: This trial was designed to test the hypothesis that shock efficacy during follow-up is not impaired in patients implanted without defibrillation (DF) testing during first implantable cardioverter-defibrillator (ICD) implantation. METHODS AND RESULTS: Between February 2011 and July 2013, 107...

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.)

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.

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.

Efficacy test of a toothpaste in reducing extrinsic dental stain

Science.gov (United States)

Agustanti, A.; Ramadhani, S. A.; Adiatman, M.; Rahardjo, A.; Callea, M.; Yavuz, I.; Maharani, D. A.

2017-08-01

This clinical trial compared the external dental stain reduction achieved by tested toothpaste versus placebo in adult patients. In this double-blind, parallel, randomised clinical trial, 45 female volunteers with a mean age of 20 years old were included. All study subjects front teeth were topically applicated with Silver Diamine Fluoride (SDF) to create external dental stains. Subjects were randomized into test (n=22) and control (n=23) groups. Toothpastes were used for two days to analyse the effects of removing external stains on the labial surfaces of all anterior teeth. VITA Easyshade Advance 4.0 was used to measure dental extrinsic stains changes. The analysis showed statistically significant efficacy of the tested toothpaste in reducing external dental stain caused by SDF, comparing to the placebo toothpaste, after one and two days of usage. The tested toothpaste was effective in reducing dental stain.

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

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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 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.

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

Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy.

Science.gov (United States)

Watanabe, Satoru; Chan, Kitti Wing-Ki; Dow, Geoffrey; Ooi, Eng Eong; Low, Jenny G; Vasudevan, Subhash G

2016-03-01

Although the antiviral drug celgosivir, an α-glucosidase I inhibitor, is highly protective when given twice daily to AG129 mice infected with dengue virus, a similar regimen of twice daily dosing did not significantly reduce serum viral loads in patients in a recent clinical trial. This failure presumably might reflect the initiation of treatment when patients were already viremic. To better mimic the clinical setting, we used viruses isolated from patients to develop new mouse models of DENV1 and DENV2 infection and employed the models to test the twice daily treatment, begun either on the day of infection or on the third day post-infection, when the mice had peak of viremia. We found that, although the treatment started on day 0 was effective on viral load reduction, it provided no benefit when begun on day 3, indicating that in vivo antiviral efficacy becomes less prominent once viremia reaches the peak level. To determine if the therapeutic regimen in humans could be improved, we tested regimen of four-times daily treatment and found that the treatment significantly reduced viremia, suggesting that a similar regimen may be effective in a human clinical trial. A new clinical trial to investigate an altered dosing regimen has been approved (NCT02569827). Copyright © 2016 Elsevier B.V. All rights reserved.

Biology and genomics of an historic therapeutic Escherichia coli bacteriophage collection

DEFF Research Database (Denmark)

Baig, Abiyad; Colom, Joan; Barrow, Paul

2017-01-01

We have performed microbiological and genomic characterization of an historic collection of nine bacteriophages, specifically infecting a K1 E. coli O18:K1:H7 ColV+ strain. These phages were isolated from sewage and tested for their efficacy in vivo for the treatment of systemic E. coli infection...... in a mouse infection model by Smith and Huggins (1982). The aim of the study was to identify common microbiological and genomic characteristics, which co-relate to the performance of these phages in in vivo study. These features will allow an informed selection of phages for use as therapeutic agents...

Test Anxiety & Its Relation to Perceived Academic Self-Efficacy among Al Hussein Bin Talal University Students

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sa'ad alzboon, Habis

2016-01-01

This study aimed to identify the degree of perceived academic self-efficacy and the relationship nature between test anxiety and perceived academic self-efficacy among students of Al Hussein Bin Talal University (AHU). Moreover, to identify the degree of available statistical significance differences that are attributed to gender, college and…

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.

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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.

Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system

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Tsuruta James K

2012-01-01

Full Text Available Abstract Background Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive. Methods Sprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment. Results We found that 3 MHz ultrasound delivered with 2.2 Watt per square cm power for fifteen minutes was necessary to deplete spermatocytes and spermatids from the testis and that this treatment significantly reduced epididymal sperm reserves. 3 MHz ultrasound treatment reduced total epididymal sperm count 10-fold lower than the wet-heat control and decreased motile sperm counts 1,000-fold lower than wet-heat alone. The current treatment regimen provided nominally more energy to the treatment chamber than Fahim's originally reported conditions of 1 MHz ultrasound delivered at 1 Watt per square cm for ten minutes. However, the true spatial average intensity, effective radiating area and power output of the transducers used by Fahim were not reported, making a direct comparison impossible. We found that germ cell depletion was most uniform and effective when we rotated the therapeutic transducer to mitigate non-uniformity of the beam field. The lowest sperm count was achieved when the coupling medium (3% saline was held at 37 degrees C and two consecutive 15-minute treatments of 3 MHz ultrasound at 2.2 Watt per square cm were separated by 2 days. Conclusions The non-invasive nature of ultrasound and its efficacy in reducing sperm count make therapeutic ultrasound a promising candidate for a male contraceptive. However, further studies must be conducted to confirm its efficacy in providing a contraceptive effect, to test the

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.

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

Directory of Open Access Journals (Sweden)

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.

Evaluation of preservative efficacy in pharmaceutical products: the use of psychrotolerant, low-nutrient preferring microbes in challenge tests.

Science.gov (United States)

Charnock, C; Otterholt, E

2012-10-01

Preservative efficacy in medicines is typically investigated using challenge tests. In such tests, the product is artificially contaminated with a high concentration of standard bacterial and fungal test strains such as Pseudomonas aeruginosa and Candida albicans. The rate and extent of reductions in inoculum viability over a specified period forms the basis for acceptance/rejection of preservative efficacy. None of the strains named for inclusion in the challenge test outlined in the European Pharmacopoeia are associated with the contamination of high-quality water used in pharmaceutical production. Alpha- and Betaproteobacteria are easily the most common microbes in waters intended for pharmaceutical production. In addition, none of the standard test strain panel prefer low-nutrient, dilute conditions or grow at or around refrigeration temperatures. This is important because the water activity and nutrient content of medicines can vary greatly and medicines are often stored cold. We investigate the relevance of these factors when testing preservative efficacy by including other strains in challenge tests. Psychrotolerant, low-nutrient preferring strains (Beta- and Alphaproteobacteria and a yeast) were isolated from pristine waters. These were compared in challenge tests with C. albicans and P. aeruginosa using different storage temperatures. Pharmaceutical products differing widely in water-content, pH and preservative systems were included in the study. Regardless of the type of medicine tested C. albicans always showed superior survival characteristics to the yeast isolate (Cryptococcus terricola). One of the three screened bacterial strains (a Sphingomonas sp.) survived significantly better than P. aeruginosa in all but one product tested. However, the results for all products taken together cannot easily be explained by reference to this strain's psychrotolerancy or its preference for dilute, low-nutrient environments. This study supports previous work

A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

Science.gov (United States)

Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

2011-02-01

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

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.

[Efficacy of balneotherapy in cholelithiasis].

Science.gov (United States)

Gorbunov, A Iu; Vakhrushev, Ia M

2011-01-01

To assess therapeutic efficacy of mineral water Uvinskaya at a prestone stage of cholelithiasis. A total of 135 cholelithiasis patients entered the trial. Of them 57 patients had a prestone stage and 78--stone stage of the disease. The stages were verified by clinical data, findings of dynamic hepatobiliscintigraphy, biochemical bile tests, anatomoemission spectroscopy with induction-bound plasma. 57 patients at prestone stage of cholelithiasis received balneotherapy with mineral water Uvinskaya. The treatment relieved pain syndrome, dyspeptic symptoms, enhanced absorption-excretion function of the liver, prolonged the time of maximal gall-bladder filling, shortened radiopharmaceutical half-life in the gall-bladder, raised the level of trace elements (magnesium, iron, potassium) in the bile, improved gall-bladder contraction, lithogenic bile characteristics. Mineral water Uvinskaya has a positive effect in a physical-chemical stage of cholelithiasis.

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

Science.gov (United States)

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

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

Efficacy of immunoassay chromatography test for hepatitis-C antibodies detection

International Nuclear Information System (INIS)

Batool, A.; Khan, M.I.; Bano, K.A.

2009-01-01

To asses the efficacy of commercially available tests device method for anti HCV detection. Methods: Total 2000 blood samples for detection of anti HCV were screened initially by immuno chromatographic method. Those found positive on initial screening were re-tested by ELISA method at the Biochemistry Laboratory of the Pakistan Medical Research Council, Fatima Jinnah Medical College, Lahore. Results: Out of a total of 2,000 blood samples, 177 were found to be initially reactive/positive for anti-HCV with immuno chromatographic method. When these reactive/positive samples were retested for confirmation with ELISA, 47 blood samples were found to have tested falsely positive for anti-HCV. Overall 2.35% of blood samples were found to be tested false positive for anti-HCV by immuno chromatographic device method. Conclusions: Immuno chromatographic device method test is rapid and simple, which can be used in setting with limited facility when rapid testing is required. However it should not be used as sole criteria for diagnosis but should serve the purpose of initial screening only. Further research is required to establish the reliability of such devices for their specificity and sensitivity. (author)

Psychometric Testing of the Self-Efficacy for Interdisciplinary Plans of Care Scale.

Science.gov (United States)

Molle, Elizabeth; Froman, Robin

2017-01-01

Computerized interdisciplinary plans of care have revitalized nurse-centric care plans into dynamic and meaningful electronic documents. To maximize the benefits of these documents, it is important to understand healthcare professionals' attitudes, specifically their confidence, for making computerized interdisciplinary care plans useful and meaningful documents. The purpose of the study was to test the psychometric properties of the Self-Efficacy for Interdisciplinary Plans of Care instrument intended to measure healthcare professionals' self-efficacy for using such documents. Content validity was assessed by an expert review panel. Content validity indices ranged from 0.75 to 1.00, with a scale CVI of 0.94. A sample of 389 healthcare providers completed the 14-item instrument. Principal axis factoring was used to assess factor structure. The exploratory factor analysis yielded a single-factor structure accounting for 71.76% of covariance. Cronbach internal consistency coefficient for the single factor solution was .97. The corrected item-total correlations ranged from 0.71 to 0.90. The coefficient of stability, during a 2-week period, with a subset of the sample (n = 38), was estimated at 0.82. The results of this study suggest that the Self-Efficacy for Interdisciplinary Plans of Care has sturdy reliability and validity for measuring the self-efficacy of healthcare providers to make computerized interdisciplinary plans of care meaningful and useful documents.

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

Science.gov (United States)

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].

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Annular phased array transducer for preclinical testing of anti-cancer drug efficacy on small animals.

Science.gov (United States)

Kujawska, Tamara; Secomski, Wojciech; Byra, Michał; Postema, Michiel; Nowicki, Andrzej

2017-04-01

A technique using pulsed High Intensity Focused Ultrasound (HIFU) to destroy deep-seated solid tumors is a promising noninvasive therapeutic approach. A main purpose of this study was to design and test a HIFU transducer suitable for preclinical studies of efficacy of tested, anti-cancer drugs, activated by HIFU beams, in the treatment of a variety of solid tumors implanted to various organs of small animals at the depth of the order of 1-2cm under the skin. To allow focusing of the beam, generated by such transducer, within treated tissue at different depths, a spherical, 2-MHz, 29-mm diameter annular phased array transducer was designed and built. To prove its potential for preclinical studies on small animals, multiple thermal lesions were induced in a pork loin ex vivo by heating beams of the same: 6W, or 12W, or 18W acoustic power and 25mm, 30mm, and 35mm focal lengths. Time delay for each annulus was controlled electronically to provide beam focusing within tissue at the depths of 10mm, 15mm, and 20mm. The exposure time required to induce local necrosis was determined at different depths using thermocouples. Location and extent of thermal lesions determined from numerical simulations were compared with those measured using ultrasound and magnetic resonance imaging techniques and verified by a digital caliper after cutting the tested tissue samples. Quantitative analysis of the results showed that the location and extent of necrotic lesions on the magnetic resonance images are consistent with those predicted numerically and measured by caliper. The edges of lesions were clearly outlined although on ultrasound images they were fuzzy. This allows to conclude that the use of the transducer designed offers an effective noninvasive tool not only to induce local necrotic lesions within treated tissue without damaging the surrounding tissue structures but also to test various chemotherapeutics activated by the HIFU beams in preclinical studies on small animals

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 potential of bryophytes and derived compounds against cancer

Directory of Open Access Journals (Sweden)

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.

Potential Bedside Utility of the Clock-Drawing Test in Evaluating Rapid Therapeutic Response in the Natural Course of Schizophrenia: A Preliminary Study.

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Ransing, Ramdas Sarjerao; Khairkar, Praveen Homdeorao; Mishra, Kshirod; Sakekar, Gajanan

2017-01-01

The Clock-Drawing Test (CDT) is a brief, relatively time-efficient, easy to administer at bedside, and well-proven cognitive screening test that assesses a broad range of cognitive abilities in stroke, delirium, and dementia. However, challenges of comprehensive therapeutic outcome evaluations in schizophrenia can also be potentially overcome using CDT. The authors aimed to measure the therapeutic outcome using CDT in 101 schizophrenia patients, irrespective of their diagnostic subtypes. A repeated measures analysis of variance found that improvements on CDT and the Positive and Negative Syndrome Scale were closely correlated, reflecting critical information about therapeutic response measures in schizophrenia.

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

Science.gov (United States)

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.

A Novel Approach for Effectively Treating SCI Pain, Improving Opioid Efficacy, and Preventing Opioid-Induced Constipation: Key Role of Toll-Like Receptor 4 (TLR4)

Science.gov (United States)

2016-12-01

tested whether performing midline 150-kDyn contusion SCI at T9 with 1 s dwell elicited more robust pain symptoms. For locomotor recovery (BBB scale...addition, we tested the hypotheses that acute morphine would worsen locomotor recovery and chronic neuropathic pain, and that acute (+)-naltrexone could...This proposal will test a clinically relevant therapeutic, (+)-naltrexone, that we predict will improve the efficacy of opioids for controlling SCI

A Novel Approach for Effectively Treating SCI Pain, Improving Opioid Efficacy, and Preventing Opioid Induced Constipation: Key Role of Toll-Like Receptor 4 (TLR4)

Science.gov (United States)

2016-10-01

tested whether performing midline 150-kDyn contusion SCI at T9 with 1 s dwell elicited more robust pain symptoms. For locomotor recovery (BBB scale...addition, we tested the hypotheses that acute morphine would worsen locomotor recovery and chronic neuropathic pain, and that acute (+)-naltrexone could...This proposal will test a clinically relevant therapeutic, (+)-naltrexone, that we predict will improve the efficacy of opioids for controlling SCI

Testing the Effectiveness of Therapeutic Showering in Labor.

Science.gov (United States)

Stark, Mary Ann

: Therapeutic showering is a holistic nursing intervention that is often available and supports physiologic labor. The purpose of this study was to compare the effectiveness of therapeutic showering with usual care during active labor. Research questions were as follows: Are there significant differences between women who showered 30 minutes during active labor and those who received usual labor care in anxiety, tension, relaxation, pain, discomfort, and coping? Is there a difference in use of obstetric interventions between groups? A convenience sample of healthy low-risk women in active labor was recruited (N = 32). A pretest posttest control group repeated-measures design was used. Participants were randomized to treatment group (n = 17), who showered for 30 minutes, or to control group (n = 14) who received usual labor care. Women evaluated pain, discomfort, anxiety, tension, coping, and relaxation at enrollment, again 15 minutes after entering the shower or receiving usual care, then again 30 minutes after entering the shower or receiving usual care. Chart reviews after delivery recorded obstetric interventions. The showering group had statistically significant decreases in pain, discomfort, anxiety and tension, and significant increase in relaxation. There were no differences in use of obstetric interventions. Therapeutic showering was effective in reducing pain, discomfort, anxiety, and tension while improving relaxation and supporting labor in this sample.

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.

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

Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids

OpenAIRE

Bazelet, Corinna S.; Thompson, Aileen C.; Naskrecki, Piotr

2016-01-01

The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet...

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.

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

Science.gov (United States)

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

Science.gov (United States)

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].

Science.gov (United States)

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

NARCIS (Netherlands)

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

Model tests for the efficacy of disinfectants on surfaces. IV. Communication: dependence of test results on the amount of contamination and the kind of active substance.

Science.gov (United States)

Peters, J; Spicher, G

1998-12-01

In the assessment of efficacy of surface disinfectants, many influencing factors have to be taken into account. One essential item is whether the surface to be disinfected is clean or soiled. Among the feasible soilings, the blood is of particular consequences because it ads impediments to many disinfecting agents. This paper shows to what extent the impairment of the efficacy of typical active agents depends on the blood burden of the surfaces. Therefore, test surfaces (varnished plywood) were contaminated with 0.01 to 0.08 ml of coagulating blood per test area (3 cm2). The blood contained cells of Staphylococcus aureus as test germs. The disinfection was effected by immersing the test objects in the disinfecting solution for 5 seconds and mingling the adhering disinfecting solution (about 0.02 ml) with the coagulated blood on the test surface with a glass spatula for about 20 seconds. Subsequently, the test objects remained in a horizontal position at room conditions for 4 hours and then the numbers of surviving test germs were determined. The graphical representation of the results shows that the efficacy curves of formaldehyde and phenol lie very closely together, i.e. their effect is hardly impaired by the different blood burdens of the test areas. The efficacy curves of glutaraldehyde, peracetic acid, chloramine T, and quaternary ammonium compounds lie very far apart from each other. To achieve the same microbicidal effect (log N/N0 = -5) when the contaminating amount is raised from 10 microliters/3 cm2 to 80 microliters/3 cm2, the concentration of chloramine T has to be raised by a factor of 5.4, peracetic acid by a factor of 9, glutaraldehyde by a factor of 24, quaternary ammonium compound even by a factor of 67. Ethanol and sodium hypochlorite showed a divergent behaviour. For ethanol, the efficacy diminution produced by increasing the contamination amount by a factor of 4 can be compensated by raising the concentration from 50% to about 70%. But again and

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

NARCIS (Netherlands)

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 and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi from Ghana and Gabon

Directory of Open Access Journals (Sweden)

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.

Influence of drug colour on perceived drug effects and efficacy.

Science.gov (United States)

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.

Husbands' perceptions of their wives' breast cancer coping efficacy: testing congruence models of adjustment.

Science.gov (United States)

Merluzzi, Thomas V; Martinez Sanchez, MaryAnn

2018-01-01

Recent reviews have reinforced the notion that having a supportive spouse can help with the process of coping with and adjusting to cancer. Congruence between spouses' perspectives has been proposed as one mechanism in that process, yet alternative models of congruence have not been examined closely. This study assessed alternative models of congruence in perceptions of coping and their mediating effects on adjustment to breast cancer. Seventy-two women in treatment for breast cancer and their husbands completed measures of marital adjustment, self-efficacy for coping, and adjustment to cancer. Karnofsky Performance Status was obtained from medical records. Wives completed a measure of self-efficacy for coping (wives' ratings of self-efficacy for coping [WSEC]) and husbands completed a measure of self-efficacy for coping (husbands' ratings of wives' self-efficacy for coping [HSEC]) based on their perceptions of their wives' coping efficacy. Interestingly, the correlation between WSEC and HSEC was only 0.207; thus, they are relatively independent perspectives. The following three models were tested to determine the nature of the relationship between WSEC and HSEC: discrepancy model (WSEC - HSEC), additive model (WSEC + HSEC), and multiplicative model (WSEC × HSEC). The discrepancy model was not related to wives' adjustment; however, the additive ( B =0.205, P <0.001) and multiplicative ( B =0.001, P <0.001) models were significantly related to wives' adjustment. Also, the additive model mediated the relationship between performance status and adjustment. Husbands' perception of their wives' coping efficacy contributed marginally to their wives' adjustment, and the combination of WSEC and HSEC mediated the relationship between functional status and wives' adjustment, thus positively impacting wives' adjustment to cancer. Future research is needed to determine the quality of the differences between HSEC and WSEC in order to develop interventions to optimize the

Relationships among sexual self-concept and sexual risk cognition toward sexual self-efficacy in adolescents: cause-and-effect model testing.

Science.gov (United States)

Hsu, Hsiu-Yueh; Yu, Hsing-Yi; Lou, Jiunn-Horng; Eng, Cheng-Joo

2015-04-01

Sexual self-efficacy plays an important role in adolescents' sexual health. The aim of this study was to test a cause-and-effect model of sexual self-concept and sexual risk cognition toward sexual self-efficacy in adolescents. The study was a cross-sectional survey. Using a random sampling method, a total of 713 junior nursing students were invited to participate in the study, and 465 valid surveys were returned, resulting in a return rate of 65.2%. The data was collected using an anonymous mailed questionnaire. Structural equation modeling was used to test the relationships among sexual self-concept, sexual risk cognition, and sexual self-efficacy, as well as the mediating role of sexual risk cognition. The results revealed that the postulated model fits the data well. Sexual self-concept significantly predicted sexual risk cognition and sexual self-efficacy. Sexual risk cognition significantly predicted sexual self-efficacy and had a mediating effect on the relationship between sexual self-concept and sexual self-efficacy. Based on social cognitive theory and a structural equation model technique, this study confirmed the mediating role of sexual risk cognition in the relationship between sexual self-concept and sexual self-efficacy. Also, sexual self-concept's direct and indirect effects explaining adolescents' sexual self-efficacy were found in this study. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

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.

Science Teacher Efficacy and Outcome Expectancy as Predictors of Students' End-of-Instruction (EOI) Biology I Test Scores

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Angle, Julie; Moseley, Christine

2009-01-01

The purpose of this study was to compare teacher efficacy beliefs of secondary Biology I teachers whose students' mean scores on the statewide End-of-Instruction (EOI) Biology I test met or exceeded the state academic proficiency level (Proficient Group) to teacher efficacy beliefs of secondary Biology I teachers whose students' mean scores on the…

New drugs: evidence relating to their therapeutic value after introduction to the market.

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Ujeyl, Mariam; Schlegel, Claudia; Walter, Siegbert; Gundert-Remy, Ursula

2012-02-01

Drug approval is based on three criteria: quality, efficacy, and safety. We investigated the types of study design and statistical methods employed to demonstrate safety and efficacy of proprietary medicinal products (PMPs) that were approved for use in the European Union through the centralized procedure. We retrospectively analyzed the European Public Assessment Reports of PMPs that the European Medicinal Agency approved, either initially or for extended indications, in 2009 and 2010. Data were analyzed for 39 PMPs: 64% of these were new active substances, and 36% were approved for extended indications. 46% of the PMPs had been studied in an active-control trial. In only 28%, superiority of the new PMPs compared to active control had been tested. 46% of the approvals included testing of a patient-relevant primary endpoint. The median size of population used to demonstrate safety was 1700 persons. The centralized procedure does not require comparative information from active-control trials. Accordingly, as our descriptive analysis revealed, this information is often not available at the time of market introduction. Pivotal studies only rarely clearly demonstrate an added therapeutic value of a new PMP compared to existing alternatives.

Diagnostic Efficacy of Modified Coagglutination Test in the Diagnosis of Human Brucellosis

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Mohite S.T

2013-07-01

Full Text Available Background: Laboratory help is must for thediagnosis of human brucellosis due to proteanclinical manifestations. As culture is hazardous,time consuming and less sensitive, serologicaltests are preferred for the diagnosis. Aggluti-nation tests like Rose Bengal PlateTest (RBPT, Serum Agglutination tests (SAT,2-Mercaptoethanol test (2-ME that are com-monly employed for the diagnosis either lacksensitivity or specificity. Coombs test andBrucellacapt though are sensitive and specific,workout costly. Therefore, modifiedcoagglutination test was developed and its di-agnostic efficacy was evaluated. Aims and Ob-jectives: To develop modified coagglutinationtest for the diagnosis of human brucellosis andcompare it with Coombs test. Materials andMethods: Serum samples collected from 191brucellosis patients and 100 controls were sub-jected to 2-ME, Coombs test and modifiedcoagglutination test (MCOAG. Blood culturewas performed by Castaneda’s method in all thepatients. Results: Significant difference in thepositivity rate was seen between MCOAG and2-ME. The results of MCOAG were compa-rable with Coombs test. Conclusions: Modi-fied coagglutination test is a better option toCoombs test for the serodiagnosis of brucel-losis in resource constrained countries as it issensitive, specific and cost effective.

New test method for the evaluation of the preservation efficacy of soaps at very alkaline pH made by saponification.

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Témoin-Fardini, S; Servant, J; Sellam, S

2017-10-01

The aim of this study was to develop a test method to evaluate the preservation efficacy for a specific product, a very high-alkaline liquid soap (pH around 10) made by a saponification process. Several manufacturers have experienced contamination issues with these high-pH soaps despite passing a classic preservative efficacy challenge test or even a multi-inoculation challenge test. Bacteria were isolated from contaminated soaps and were identified using 16S rRNA gene sequencing. High-alkaline-pH unpreserved soaps were tested using the Thor Personal Care internal multichallenge test method (TM206) with classical microorganisms and then with the bacterial strains isolated from various contaminated soaps (TM768). Preservatives were added to these soaps and assessed for their efficacy using the newly developed test. Four different species of bacteria (Nesterenkonia lacusekhoensis, Dermacoccus sp., Halomonas sp. and Roseomonas sp.) were identified by sequencing among the contaminants of the various soaps tested. Among these, only one bacterial species, Nesterenkonia lacusekhoensis, appeared to be responsible for the specific contamination of these high-alkaline soaps. Thus, one specific wild-type strain of Nesterenkonia lacusekhoensis, named as strain 768, was used in a new multi-inoculation test (TM768). Unlike the single inoculation challenge test, the multi-inoculation test using the Nesterenkonia strain 768 was able to predict the sensitivity of a product towards this bacterium. Among the 27 different preservatives tested, 10 were able to protect the formula against contamination with this bacterium. This study enabled the development of a test method to evaluate the efficacy of preservation using a specific bacterium, Nesterenkonia lacusekhoensis, responsible for the contamination of very alkaline soaps made by saponification and identify an appropriate preservative system. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

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.

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

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

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.

The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

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Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

2018-01-01

Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

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.

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

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Vaughan-Williams, Charles H; Raman, Jaishree; Raswiswi, Eric; Immelman, Etienne; Reichel, Holger; Gate, Kelly; Knight, Steve

2012-12-28

Zulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

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Vaughan-Williams Charles H

2012-12-01

suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

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

Efficacy of 50-G Glucose Challenge Test in The Diagnosis of Gestational Diabetes Mellitus

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Cihan İnan

2014-09-01

Full Text Available Aim: Our aim in this study was to investigate the efficacy of 50 g glucose challenge test (GCT in the diagnosis of gestational diabetes mellitus (GDM and to determine a cut-off value for screening. Methods: 50-g GCT was performed in 444 pregnant women at 24-28 gestational weeks. The threshold was taken as 130 mg/dl in order not to miss GDM cases. A plasma glucose level of ≥130 mg/dl at the first hour was considered to be a positive result and 100-g oral glucose tolerance test (OGTT was given to these women. Results: The cut-off value for 50-g GCT was found to be 145 mg/dl. The sensitivity and specificity of the test for predicting GDM at the levels of ≥145 mg/dl were determined to be 96.30% and 80.34%, respectively. The sensitivity and specificity of the test at the level of 88 mg/dl determined for fasting blood glucose cut-off value were found to be 48.15% and 70.84%, respectively. Conclusion: It was concluded that the efficacy in making diagnosis of GDM was increased at the first hour blood glucose levels of ≥145 mg/dl, especially in 50-g GCT, and fasting blood glucose level could not be a good screening test for GDM. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 181-6

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

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

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Dumonteil, Eric; Bottazzi, Maria Elena; Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, B T; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto; Hotez, Peter J

2012-09-01

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.

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.

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.

Effect of verbal persuasion on self-efficacy for pain-related diagnostic sensory testing in individuals with chronic neck pain and healthy controls - a randomized, controlled trial.

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Söderlund, Anne; Sterling, Michele

2016-01-01

The aim of this study was to investigate the differences in cold pain threshold (CTh), pressure pain threshold (PPT), cold pain tolerance (CPTo) tests, and the level of self-efficacy when self-efficacy for diagnostic sensory testing was manipulated by verbal persuasion before a testing situation in persons with neck pain and in healthy controls. A randomized experimental design was used. Twenty-one healthy volunteers and 22 individuals with either traumatic or nontraumatic chronic neck pain were recruited to participate in the study. The intervention consisted of two experimental verbal persuasion conditions: Increase self-efficacy and Decrease self-efficacy. The PPT was measured using a pressure algometer, the CTh was measured using a thermo test system, and CPTo was measured by submerging the participant's hand in ice water up to the elbow joint. On three occasions, the participants reported their self-efficacy level in performing the sensory tests. In the chronic neck pain group, there were no differences in pain threshold or tolerance. There was a difference in the self-efficacy level after verbal persuasion between the experimental conditions. In the healthy control group, the CThs increased following the condition that aimed to increase self-efficacy. No other differences were observed in the healthy controls. A short verbal persuasion in the form of manipulative instructions seems to have a marginal effect on the individual's self-efficacy levels in the chronic neck pain group and a slight influence on the results of sensory testing in healthy controls.

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

In silico prediction of novel therapeutic targets using gene-disease association data.

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Ferrero, Enrico; Dunham, Ian; Sanseau, Philippe

2017-08-29

Target identification and validation is a pressing challenge in the pharmaceutical industry, with many of the programmes that fail for efficacy reasons showing poor association between the drug target and the disease. Computational prediction of successful targets could have a considerable impact on attrition rates in the drug discovery pipeline by significantly reducing the initial search space. Here, we explore whether gene-disease association data from the Open Targets platform is sufficient to predict therapeutic targets that are actively being pursued by pharmaceutical companies or are already on the market. To test our hypothesis, we train four different classifiers (a random forest, a support vector machine, a neural network and a gradient boosting machine) on partially labelled data and evaluate their performance using nested cross-validation and testing on an independent set. We then select the best performing model and use it to make predictions on more than 15,000 genes. Finally, we validate our predictions by mining the scientific literature for proposed therapeutic targets. We observe that the data types with the best predictive power are animal models showing a disease-relevant phenotype, differential expression in diseased tissue and genetic association with the disease under investigation. On a test set, the neural network classifier achieves over 71% accuracy with an AUC of 0.76 when predicting therapeutic targets in a semi-supervised learning setting. We use this model to gain insights into current and failed programmes and to predict 1431 novel targets, of which a highly significant proportion has been independently proposed in the literature. Our in silico approach shows that data linking genes and diseases is sufficient to predict novel therapeutic targets effectively and confirms that this type of evidence is essential for formulating or strengthening hypotheses in the target discovery process. Ultimately, more rapid and automated target

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.

Role of Academic Self-efficacy and Social Support on Nursing Students' Test Anxiety.

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Warshawski, Sigalit; Bar-Lev, Oshra; Barnoy, Sivia

2018-05-25

Associations between test anxiety, academic self-efficacy (ASE), and social support through social media have not been fully explored. The purposes were to explore associations between test anxiety, ASE, and social support from social media and to examine differences in test anxiety by students' year of studies and cultural background. This study used a cross-sectional, descriptive design. The sample comprised first- and fourth-year nursing students (n = 240) attending a baccalaureate nursing program in Israel. Higher ASE and support through social media were related to lower test anxiety. Fourth-year students and Jewish students had higher ASE than first-year and Arab students, who received more support on social media than Jewish students. Developing learning strategies designed to increase students' ASE and reduce test anxiety is warranted. Social media as an educational tool can be adopted for this purpose.

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.

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.

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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.

Progression of Ebola Therapeutics During the 2014-2015 Outbreak.

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Mendoza, Emelissa J; Qiu, Xiangguo; Kobinger, Gary P

2016-02-01

The recent Ebola virus (EBOV) outbreak in West Africa was the deadliest EBOV epidemic in history, highlighting the need for a safe and efficacious treatment against EBOV disease (EVD). In the absence of an approved treatment, experimental drugs were utilized under compassionate grounds hoping to diminish EVD-associated morbidity and mortality. As more data were collected from safety studies, Phase II/III clinical trials were introduced in Guinea, Sierra Leone, and Liberia to test promising candidates, including small-molecule drugs, RNA-based treatments, and antibody-based therapies. In this review, we summarize the use of, and preliminary observations from, current clinical trials with EVD therapeutics, shedding light on experimental drug selection, emergency clinical evaluation, and the impact these factors may have on future infectious disease outbreaks. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

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.

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

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

Benzimidazole resistance of sheep nematodes in Norway confirmed through controlled efficacy test

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Domke Atle V

2012-08-01

Full Text Available Abstract Background Resistance against benzimidazoles (BZ has recently been detected in Norwegian sheep flocks through a large scale prevalence survey based on the faecal egg count reduction test (FECRT. The use of this test in combination with bulk larval culture only gives an indication of which gastrointestinal nematodes genera that are involved and these results have to be confirmed by a controlled efficacy test (CET to get accurate information about resistant nematodes populations at species level. A CET was therefore performed with larvae from two flocks where BZ resistance was previously detected through FECRT. Results The latter test confirmed the previous results in both flocks. In flock A, the BZ resistant nematode population consisted solely of Haemonchus contortus, whereas H. contortus and Teladorsagia circumcincta comprised the resistant worm population in flock B. Conclusions Some discrepancies that have been recorded between FECRT and CET results regarding time for post-treatment coproscopical examination and a temporary suppression of faecal egg excretion are discussed.

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

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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.

Development and psychometric testing of the 'Motivation and Self-Efficacy in Early Detection of Skin Lesions' index.

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Dyson, Judith; Cowdell, Fiona

2014-12-01

To develop and psychometrically test the Motivation and Self-Efficacy in Early Detection of Skin Lesions Index. Skin cancer is the most frequently diagnosed cancer worldwide. The primary strategy used to prevent skin cancer is promotion of sun avoidance and the use of sun protection. However, despite costly and extensive campaigns, cases of skin cancer continue to increase. If found and treated early, skin cancer is curable. Early detection is, therefore, very important. The study was conducted in 2013. Instrument Development. A literature review and a survey identified barriers (factors that hinder) and levers (factors that help) to skin self-examination. These were categorized according to a the Theoretical Domains Framework and this formed the basis of an instrument, which was tested for validity and reliability using confirmatory factor analysis and Cronbach's alpha respectively. A five-factor 20-item instrument was used that tested well for reliability and construct validity. Test-retest reliability was good for all items and domains. The five factors were: (i) Outcome expectancies; (ii) Intention; (iii) Self-efficacy; (iv) Social influences; (v) Memory. The Motivation and Self-Efficacy in Early Detection of Skin Lesions Index provides a reliable and valid method of assessing barriers and levers to skin self-examination. The next step is to design a theory-based intervention that can be tailored according to individual determinants to behaviour change identified by this instrument. © 2014 John Wiley & Sons Ltd.

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

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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.

Positive results of serological tests for syphilis in pregnancy – diagnostic and therapeutic problems, report of two cases

OpenAIRE

Marta Koper; Agnieszka B. Serwin; Anna Baran; Iwona Flisiak

2015-01-01

Introduction. Undiagnosed and untreated syphilis in pregnancy may result in subsequent complications: early fetal loss, stillbirth, low birth weight of infants and newborns with congenital syphilis. Objective. To analyze diagnostic and therapeutic dilemmas of positive results of serological tests for syphilis (STS) in pregnancy. Case reports. We present two cases of pregnant women, hospitalized in our department due to positive results of serological tests for syphilis, pe...

Methods and Guidance for Testing the Efficacy of Antimicrobials against Biofilm Bacteria on Hard, Non-Porous Surfaces

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EPA is announcing the availability of two test methods (MB-19 and MB-20) for evaluating the efficacy of antimicrobial pesticides against two biofilm bacteria, Pseudomonas aeruginosa and Staphylococcus aureus.

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

Science.gov (United States)

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,…

Role of Academic Self-Efficacy in Moderating the Relation between Task Importance and Test Anxiety

Science.gov (United States)

Nie, Youyan; Lau, Shun; Liau, Albert K.

2011-01-01

Emphasizing task importance, which is regarded as a way of motivating engaged behavior, may increase an individual's anxiety. The present research investigated whether academic self-efficacy could moderate the maladaptive relation between task importance and test anxiety. 1978 and 1670 Grade 9 Singaporean students participated in a survey related…

HIV coping self-efficacy: a key to understanding stigma and HIV test acceptance among incarcerated men in Jamaica.

Science.gov (United States)

Andrinopoulos, Katherine; Kerrigan, Deanna; Figueroa, J Peter; Reese, Richard; Ellen, Jonathan M

2010-03-01

Although prisons have been noted as important venues for HIV testing, few studies have explored the factors within this context that may influence HIV test acceptance. Moreover, there is a dearth of research related to HIV and incarcerated populations in middle and low-income countries, where both the burden of HIV and the number of people incarcerated is higher compared to high-income countries. This study explores the relationship between HIV coping self-efficacy, HIV-related stigma, and HIV test acceptance in the largest prisons in Jamaica. A random sample of inmates (n=298) recruited from an HIV testing demonstration project were asked to complete a cross-sectional quantitative survey. Participants who reported high HIV coping self-efficacy (adjusted odds ratio (AOR) 1.86: 95% confidence interval CI 1.24-2.78, p-value=0.003), some perceived risk of HIV (AOR 2.51: 95% (CI) 1.57-4.01, p-value=0.000), and low HIV testing stigma (AOR 1.71: 95% CI 1.05-2.79, p-value=0.032) were more likely to test for HIV. Correlates of HIV coping self-efficacy included external and internal HIV stigma (AOR 1.28: 95% CI 1.25-1.32, p-value=0.000 and AOR 1.76: 95% CI 1.34-2.30, p-value=0.000, respectively), social support (AOR 2.09: 95% CI 1.19-3.68, p-value=0.010), and HIV knowledge (AOR 2.33: 95% CI 1.04-5.22, p-value=0.040). Policy and programs should focus on the interrelationships of these constructs to increase participation in HIV testing in prison.

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

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.

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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

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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.

Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing

International Nuclear Information System (INIS)

Penitzka, S.; Wannenmacher, M.; Steinvorth, S.; MIT, Cambridge, MT; Sehlleier, S.; Universitaetsklinikum Wuerzburg; Fuss, M.; Texas Univ., San Antonio, TX; Wenz, F.; Universitaetsklinikum Mannheim

2002-01-01

Purpose: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. Patients and Method: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). Results: Patients with SCLC showed test results significantly below average before PCI (n=28, mean IQ=83, SD=17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). Conclusion: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible. (orig.) [de

Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test.

Science.gov (United States)

Novobilský, Adam; Amaya Solis, Natalia; Skarin, Moa; Höglund, Johan

2016-12-01

Anthelmintic resistance (AR) to Fasciola hepatica is emerging worldwide. Recently, AR to the adulticide compound albendazole (ABZ) was shown in Argentina and Spain. In Sweden, ABZ treatment failure against F. hepatica was first reported in sheep in 2012. The present study tested the efficacy of ABZ and triclabendazole (TCBZ) in sheep naturally infected with F. hepatica using a combination of three different diagnostic methods: faecal egg counts (FEC), coproantigen ELISA (cELISA) and Fasciola egg hatch test (FEHT). Two deworming trials, in November 2014 and January 2015, were performed on two sheep farms (farms A and B) in south-western Sweden. Except ABZ in November, treatment with ABZ or TCBZ achieved sufficient efficacy (97-100%) against adult F. hepatica on farm A. In contrast, ABZ treatment failed in the sheep flock on farm B, despite low initial faecal egg output. On farm B, ABZ efficacy based on FEC was 67% (95% CI: 35-84) and four of eight ewes tested were coproantigen-positive 21 days post-treatment. Ovicidal activity of ABZ against Fasciola eggs in isolates from both farms and one additional bovine isolate were tested by FEHT to exclude the presence of juvenile flukes and other factors such as dosing failure and poor quality of drug product. Irrespective of drug trial, data from FEHT showed significantly lower ovicidal activity of ABZ for the ovine farm B isolate than for the isolate from farm A. This confirms that the low efficacy of ABZ in sheep flock B was associated with ABZ resistance. Overall, the usefulness of three complementary methods for detection of ABZ resistance in the field was demonstrated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats

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Arndt, David L.; Peterson, Christy J.; Cain, Mary E.

2015-01-01

Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression. PMID:26154768

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

Directory of Open Access Journals (Sweden)

David L Arndt

Full Text Available Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC, standard (SC, or isolated (IC conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p. was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg rats and EC-fluoxetine (20 mg/kg rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

Science.gov (United States)

Arndt, David L; Peterson, Christy J; Cain, Mary E

2015-01-01

Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

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.

Principal Self-Efficacy and Work Engagement: Assessing a Norwegian Principal Self-Efficacy Scale

Science.gov (United States)

Federici, Roger A.; Skaalvik, Einar M.

2011-01-01

One purpose of the present study was to develop and test the factor structure of a multidimensional and hierarchical Norwegian Principal Self-Efficacy Scale (NPSES). Another purpose of the study was to investigate the relationship between principal self-efficacy and work engagement. Principal self-efficacy was measured by the 22-item NPSES. Work…

The Zombie Plot: A Simple Graphic Method for Visualizing the Efficacy of a Diagnostic Test.

Science.gov (United States)

Richardson, Michael L

2016-08-09

One of the most important jobs of a radiologist is to pick the most appropriate imaging test for a particular clinical situation. Making a proper selection sometimes requires statistical analysis. The objective of this article is to introduce a simple graphic technique, an ROC plot that has been divided into zones of mostly bad imaging efficacy (ZOMBIE, hereafter referred to as the "zombie plot"), that transforms information about imaging efficacy from the numeric domain into the visual domain. The numeric rationale for the use of zombie plots is given, as are several examples of the clinical use of these plots. Two online calculators are described that simplify the process of producing a zombie plot.

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.

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.

Effect of verbal persuasion on self-efficacy for pain-related diagnostic sensory testing in individuals with chronic neck pain and healthy controls – a randomized, controlled trial

Directory of Open Access Journals (Sweden)

Söderlund A

2016-03-01

Full Text Available Anne Söderlund,1 Michele Sterling,2 1Physiotherapy, School of Health, Care and Social Welfare, Mälardalen University, Västerås, Sweden; 2Centre for National Research on Disability and Rehabilitation Medicine (CONROD, Menzies Health Institute Queensland, Griffith University, Parklands, Australia Abstract: The aim of this study was to investigate the differences in cold pain threshold (CTh, pressure pain threshold (PPT, cold pain tolerance (CPTo tests, and the level of self-efficacy when self-efficacy for diagnostic sensory testing was manipulated by verbal persuasion before a testing situation in persons with neck pain and in healthy controls. A randomized experimental design was used. Twenty-one healthy volunteers and 22 individuals with either traumatic or nontraumatic chronic neck pain were recruited to participate in the study. The intervention consisted of two experimental verbal persuasion conditions: Increase self-efficacy and Decrease self-efficacy. The PPT was measured using a pressure algometer, the CTh was measured using a thermo test system, and CPTo was measured by submerging the participant's hand in ice water up to the elbow joint. On three occasions, the participants reported their self-efficacy level in performing the sensory tests. In the chronic neck pain group, there were no differences in pain threshold or tolerance. There was a difference in the self-efficacy level after verbal persuasion between the experimental conditions. In the healthy control group, the CThs increased following the condition that aimed to increase self-efficacy. No other differences were observed in the healthy controls. A short verbal persuasion in the form of manipulative instructions seems to have a marginal effect on the individual's self-efficacy levels in the chronic neck pain group and a slight influence on the results of sensory testing in healthy controls. Keywords: pressure pain threshold, cold pain threshold, cold pain tolerance, self-efficacy

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.

[Efficacy of enterocin S760 in treatment of mice with anthrax infection due to Bacillus anthracis M-71].

Science.gov (United States)

Svetoch, E A; Borzilov, A I; Eruslanov, B V; Korobova, O V; Kombarova, T I; Levchuk, V P; Teĭmurazov, M G; Stepanshin, Iu G; Marinin, L I; Diatlov, I A

2011-01-01

The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial peptide produced by Enterococcus faecium LWP760 was tested on mice infected with Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine). Intraperitoneal four-, two- or one-fold administration of the peptide in a dose of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and therapeutic (24 hours after the contamination) purposes prevented or cured the infection in 90-100% of the mice versus the 100-percent lethality in the control (untreated animals). The antimicrobial activity of enterocin S760 against B. anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is considered a novel promising antimicrobial for the treatment of grampositive and gramnegative infections.

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

Science.gov (United States)

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.

Efficacy of microtensile versus microshear bond testing for evaluation of bond strength of dental adhesive systems to enamel

NARCIS (Netherlands)

El Zohairy, A.A.; Saber, M.H.; Abdalla, A.I.; Feilzer, A.J.

2010-01-01

Objective The aim of the study was to evaluate the efficacy of the microtensile bond test (μTBS) and the microshear bond test (μSBS) in ranking four dental adhesives according to bond strength to enamel and identify the modes of failure involved. Materials and methods Forty-four caries-free human

Therapeutic Sleep for Traumatic Brain Injury

Science.gov (United States)

2017-06-01

AWARD NUMBER: W81XWH-16-1-0166 TITLE: Therapeutic Sleep for Traumatic Brain Injury PRINCIPAL INVESTIGATOR: Ravi Allada CONTRACTING...1. REPORT DATE June 2017 2. REPORT TYPE Annual 3. DATES COVERED 1June2016 - 31May2017 4. TITLE AND SUBTITLE Therapeutic Sleep for Traumatic Brain ...proposal will test the hypothesis that correcting sleep disorders can have a therapeutic effect onTraumatic Brain Injury (TBI) The majority of TBI

Maximizing the Therapeutic Efficacy of Imatinib Mesylate-Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design.

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Kassem, Mohammed A; El-Sawy, Hossam S; Abd-Allah, Fathy I; Abdelghany, Tamer M; El-Say, Khalid M

2017-01-01

This research purposed to formulate an optimized imatinib mesylate (IM)-loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y 1 ), zeta potential (Y 2 ), entrapment capacity percentage (Y 3 ), the percentage of initial drug release after 2 h (Y 4 ), and the percentage of cumulative drug release after 24 h (Y 5 ) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, -62.4 mV, 82.96%, 18.93%, and 89.45% for Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 , respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC 50 values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC 50 of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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

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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 ...

The Therapeutic Efficacy of Domestic Violence Victim Interventions.

Science.gov (United States)

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

2016-04-01

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

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

[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

Science.gov (United States)

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

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

Science.gov (United States)

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.

The Effectiveness of Cognitive-Behavioral Therapy on Alexithymia and Pain Self-Efficacy of Patients with Chronic Pain

Directory of Open Access Journals (Sweden)

Sara Saedi

2016-11-01

Full Text Available Chronic pain is one of the most common reasons for visit to primary medical centers. Evidences show that cognitive-behavioral therapy is the effective therapy in chronic pains. The present study evaluates the effectiveness of cognitive-behavioral therapy on alexithymia and pains self-efficacy of patients with chronic pain. For this purpose, in a quasi-experimental plan and pre-test and post-test kind with control group, 45 patients with chronic musculoskeletal pain who visited to the therapeutic-sanitary centers in Ahwaz city were selected by using the available sampling method and they were assigned randomly in two experimental and control groups. Groups were tested in terms of alexithymia and self-effectiveness of pain at first. Then behavioral-cognitive training was presented in the time of 8 sessions of 90 minutes to the group and after ending the training program and three month consistency period, both groups were tested in terms of alexithymia and self-efficacy of pain. analyzing data by multivariate covariance method showed that the behavioral-cognitive therapy has been effective on alexithymia and pain intensity of patients with chronic musculoskeletal pain and these effects remain on patients in the high amount in the consistency stage, too. According to the results, behavioral-cognitive therapy causes to increasing the self-efficacy of pain and reducing the alexithymia and harmful effects of pain to the least level by changing nonefficiency behaviors, correction of adverse cognitions and destructive emotions related to pain.

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.

Science.gov (United States)

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 atorvastatin in treatment of non-alcoholic fatty liver disease in patients with type Ⅱ diabetes mellitus

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FENG Mengdie

2013-07-01

Full Text Available ObjectiveTo observe the therapeutic efficacy of atorvastatin in the treatment of non-alcoholic fatty liver disease (NAFLD in patients with type Ⅱ diabetes mellitus. MethodsA total of 118 patients with type Ⅱ diabetes mellitus complicated by NAFLD, who visited the outpatient department of internal medicine or were hospitalized in our hospital from January 2010 to March 2012, were divided randomly into treatment group (n=61 and control group (n=57. Both groups received liver protection therapy and blood glucose control, and atorvastatin (20 mg/d was administered as an addition in the treatment group. The clinical symptoms, body mass index (BMI, blood levels of total cholesterol (TC, triglyceride (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, alanine aminotransferase (ALT, and aspartate aminotransferase (AST, and liver B-mode ultrasound findings were evaluated before and after 6 months of treatment. The enumeration data were analysed by chi-square test, the indices before and after treatment were compared by t-test. ResultsAfter 6 months of treatment, the treatment group had a significantly decreased clinical symptom score (t=21.07, P=0.0000, significantly decreased blood levels of TC ((6.80±1.20 vs (5.24±0.67 mmol/L, t=8.87, P=0000, LDL-C ((4.38±0.75 vs (3.45±0.68 mmol/L, t=7.17, P=0.0000, TG ((2.14±0.56 vs (1.69±0.34 mmol/L, t=5.36, P=0.0000, ALT ((61±11 vs (46±9 U/L, t=8.24, P=0.0000, and AST ((53±14 vs (41±12 U/L, t=5.08, P=0.0000, and increased blood HDL-C level (t=1.95, P＞0.05, but there was no significant change in BMI (t=1.84, P=0.0683. No significant changes in these indices were found in the control group (P＞0.05. Both groups showed changes in liver density as measured by B-mode ultrasound, but there was no significant difference between them (P＞0.05. No adverse events occurred in either group. ConclusionAtorvastatin can markedly relieve clinical symptoms and lower

Linking Affective Commitment, Career Self-Efficacy, and Outcome Expectations: A Test of Social Cognitive Career Theory

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Conklin, Amanda M.; Dahling, Jason J.; Garcia, Pablo A.

2013-01-01

The authors tested a model based on the satisfaction model of social cognitive career theory (SCCT) that links college students' affective commitment to their major (the emotional identification that students feel toward their area of study) with career decision self-efficacy (CDSE) and career outcome expectations. Results indicate that CDSE…

New testing options for diagnosing and grading dry eye disease.

Science.gov (United States)

Foulks, Gary N; Pflugfelder, Stephen C

2014-06-01

To describe new options for diagnosis and severity grading of dry eye disease. Perspective on technological advancements to identify tear dysfunction and their value in diagnosing and grading dry eye disease. Evidence is presented on new and evolving technologies to measure tear stability, composition, and meniscus height and their role in dry eye diagnosis and therapeutic efficacy grading is assessed. Evolving concepts regarding pathogenesis and new technologies to evaluate the tears and ocular surface have improved the ability to diagnose, classify, and grade the severity of dry eye disease. New technologies include noninvasive imaging of tear stability and tear meniscus height as a measure of tear volume and tear composition (osmolarity, lacrimal factors, inflammatory mediators, growth and differentiation factors). Approved tests, such as tear osmolarity and tear imaging, are being integrated into clinical practice and may eventually supplant certain traditional tests that have greater variability and less sensitivity. Other tests, such as molecular assays of tears and conjunctival cells, are currently being used in studies investigating pathogenesis and therapeutic mechanism of action. They may eventually translate to routine clinical practice. New technologies have emerged that can noninvasively evaluate the tears and measure disease-associated compositional changes. These tests are being integrated into clinical practice and therapeutic trials for diagnosis, classification, and severity grading of dry eye disease. Copyright © 2014 Elsevier Inc. All rights reserved.

The state of the art in therapeutic nuclear medicine

International Nuclear Information System (INIS)

Allen, B.J.

2001-01-01

Radionuclide therapy can be curative or palliative in intent, and local or systemic in administration. Current therapy relies of beta emitting radioisotopes and selective carriers for the treatment of advanced tumours. The next generation of therapeutics may be alpha emitting radionuclides for subclinical, micrometastatic disease. Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT has been tested by in vitro and in vivo studies many cancers. The first phase 1 clinical trial of TAT for leukaemia with Bi-213 has concluded at the Memorial Sloan Kettering Cancer Center, a phase 1 and 2 trial of intra-lesional TAT is ongoing at Duke University with At-211 labeled Mab against cystic glioma, and a phase 1 and 2 clinical trial for intra-lesional TAT with Bi-213 of subcutaneous secondary melanoma is underway at St George Hospital

Locating therapeutic vaccines in nineteenth-century history.

Science.gov (United States)

Gradmann, Christoph

2008-06-01

This essay places some therapeutic vaccines, including particularly the diphtheria antitoxin, into their larger historical context of the late nineteenth century. As industrially produced drugs, these vaccines ought to be seen in connection with the structural changes in medicine and pharmacology at the time. Given the spread of industrial culture and technology into the field of medicine and pharmacology, therapeutic vaccines can be understood as boundary objects that required and facilitated communication between industrialists, medical researchers, public health officials, and clinicians. It was in particular in relation to evaluation and testing for efficacy in animal models that these medicines became a model for twentieth-century medicine. In addition, these medicines came into being as a parallel invention in two very distinct local cultures of research: the Institut Pasteur in Paris and the Institut für Infektionskrankheiten in Berlin. While their local cultural origins were plainly visible, the medicines played an important role in the alignment of the methods and objects that took place in bacteriology research in France and Germany in the 1890s. This article assesses the two locally specific regimes for control in France and in Imperial Germany. In France the Institut Pasteur, building on earlier successful vaccines, enjoyed freedom from scrutinizing control. The tight and elaborate system of control that evolved in Imperial Germany is portrayed as being reliant on experiences that were drawn from the dramatic events that surrounded the launching of a first example of so-called "bacteriological medicine," tuberculin, in 1890.

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.

Efficacy of escitalopram monotherapy in the treatment of major depressive disorder

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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

2004-01-01

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

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, ...

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

Pemphigus in North-Western Yemen: A therapeutic study of 75 cases.

Science.gov (United States)

Khatri, Mishri Lal

2016-01-01

The incidence of pemphigus, though not documented, seems to be quite high in Yemen. There is no universal consensus on the treatment of this disease. The aim was to evaluate the efficacy and side effects of different therapeutic regimens used in patients of pemphigus in North-Western Yemen. Seventy-five Yemeni patients (39 males and 36 females) were included. Diagnosis was based on clinical features, histopathology and the Tzanck test. Results of treatment with these different therapeutic regimens were compared: (1) dexamethasone-cyclophosphamide pulse (DCP), (2) dexamethasone pulse with oral azathioprine, (3) oral prednisolone with azathioprine, (4) oral prednisolone with oral cyclophosphamide, and (5) prednisolone monotherapy. Pemphigus vulgaris (PV) was diagnosed in 46 patients, pemphigus foliaceus (PF) in 23, pemphigus vegetans (PVEG) in 5 and pemphigus herpetiformis (PH) in one. Among the 16 patients who received regular DCP therapy, 13 were in remission for 6 months to 11 years without medications (phase 4). Remission without pharmacotherapy could not be achieved with the other regimens and steroid-induced side-effects appeared to be more than with DCP. Immunofluorescence was not available to confirm the diagnosis of pemphigus. Randomization was not done. The DCP regimen seemed to be superior to the other regimens used.

A Pilot Study to Test the Efficacy of Psychologically Based Physical Therapy Training for Treating Deployed U.S. Sailors and Marines with Musculoskeletal Injuries

Science.gov (United States)

2017-10-01

Department of Population Health , NYU Langone Medical Center, New York, NY. ****Department of Physical Therapy, Naval Medical Center Portsmouth...AWARD NUMBER: W81XWH-14-2-0146 TITLE: A Pilot Study to Test the Efficacy of Psychologically Based Physical Therapy Training for Treating...Test the Efficacy of Psychologically Based Physical Therapy Training for Treating Deployed U.S. Sailors and Marines with Musculoskeletal Injuries 5b

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.

Science.gov (United States)

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

[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.

Efficacy of kinesio taping on isokinetic quadriceps torque in knee osteoarthritis: a double blinded randomized controlled study.

Science.gov (United States)

Anandkumar, Sudarshan; Sudarshan, Shobhalakshmi; Nagpal, Pratima

2014-08-01

Double blind pre-test post-test control group design. To compare the isokinetic quadriceps torque, standardized stair-climbing task (SSCT) and pain during SSCT between subjects diagnosed with knee osteoarthritis pre and post kinesio tape (KT) application with and without tension. Strength of the quadriceps and torque producing capability is frequently found to be compromised in knee osteoarthritis. The efficacy of KT in improving isokinetic quadriceps torque in knee osteoarthritis is unknown, forming the basis for this study. Forty subjects were randomly allocated to either the experimental (therapeutic KT with tension) or control group (sham KT without tension) with the allocation being concealed. Pre and post test measurements of isokinetic quadriceps torque, SSCT and pain during SSCT were carried out by a blinded assessor. A large effect size with significant improvements in the peak quadriceps torque (concentric and eccentric at angular velocities of 90° per second and 120° per second), SSCT and pain were obtained in the experimental group when compared to the control group. Application of therapeutic KT is effective in improving isokinetic quadriceps torque, SSCT and reducing pain in knee osteoarthritis.

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.

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

Science.gov (United States)

Kannan, Rangaramanujam

2007-03-01

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

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.

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.

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.

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)

The Effectiveness of Matrix Treatment to Relapse prevention and Increase Self-Efficacy in People Withdrawing Methamphetamine

Directory of Open Access Journals (Sweden)

Siamak Ghasemnezhad

2016-08-01

Full Text Available Given the prevalence of narcotic substances and their effect on mental health of society people, it is important to pay attention the matter and adopt an approach for its treatment. The research objective is to examine the effectiveness of matrix treatment on prevent relapsing and increase self-efficacy in people withdrawing methamphetamine. In a quasi-experimental design, methamphetamine users who referred to addiction treatment centers on west of Gilanin 2015 and were eligible for involving criteria completed theself efficacy questionnaire. Then among those who got low scores on this questionnaire, there were randomly selected 30 patients that were divided into experimental and control groups (15 patients for each group. The experimental group was treated for 18 weeks and two sessions per week (36 sessions using matrix therapeutic model. The control group remained on waiting list. Both groups completed self-efficacy questionnaire at baseline, end and 90 days later (follow-up stage with urine test. The control group remained on waiting list and there were assigned only common drug treatment in the withdrawal centers. The research data was analyzed using covariance analysis and SPSS22 software. The results showed efficiency of matrix treatment method in preventing relapse and increasing self-efficacy for people withdrawal methamphetamine, which this difference was statistically significant (p<0.5. Matrix-based treatmentis effective for relapse prevention and increasing self-efficacy for people withdrawal methamphetamine.

Prematurity and parental self-efficacy: the Preterm Parenting & Self-Efficacy Checklist.

Science.gov (United States)

Pennell, Claire; Whittingham, Koa; Boyd, Roslyn; Sanders, Matthew; Colditz, Paul

2012-12-01

There is a lack of research investigating parental self-efficacy in parents of infants born preterm as well as a paucity of parental self-efficacy measures that are domain-specific and theoretically grounded. This study aimed to compare parental self-efficacy in parents of infants born term, preterm and very preterm as well as to test whether parental self-efficacy mediates the relationship between psychological symptoms and parental competence. In order to achieve this, a new measure of parental self-efficacy and parental competence relevant for the preterm population and consistent with Bandura's (1977, 1986, 1989) conceptualisation of self-efficacy was developed. Participants included 155 parents, 83 of whom were parents of very preterm (GAparents of preterm (GAparents of term born infants. Parents completed the Preterm Parenting & Self-Efficacy Checklist (the new measure), Family Demographic Questionnaire, Depression Anxiety Stress Scale and Self-Efficacy Questionnaire. This initial study indicates that the Preterm Parenting & Self-Efficacy Checklist has adequate content validity, construct validity, internal consistency and split half reliability. Contrary to expectations, parents of very preterm infants did not report significantly lower overall levels of parental self-efficacy or significantly higher levels of psychological symptoms compared to parents of preterm and term infants. Parental self-efficacy about parenting tasks mediated the relationship between psychological symptoms and self perceived parental competence as predicted. Clinical implications of the results and suggestions for future research are discussed. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

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...

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

Science.gov (United States)

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.

Effects of ascorbic acid and α-tocopherol on the therapeutic index of amphotericin B.

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Belhachemi, M H; Boucherit, K; Boucherit-Otmani, Z; Belmir, S; Benbekhti, Z

2014-12-01

Amphotericin B (AmB) remains the antifungal polyene of choice in deep fungal infections, but its high toxicity to mammalian cells limits its use. This toxicity is partly due to lipid peroxidation exerted by amphotericin B in cell membranes. The work we have undertaken focused on the one part the evaluation of the efficacy of amphotericin B in the presence of some antioxidants vitamins (vitamin C "ascorbic acid" and vitamin E "α-tocopherol") against the yeast Candida albicans ATCC 10231. Secondly, we have tested the cytotoxicity of these formulations on human red blood cells. The results showed a significant improvement in the efficiency of our formulations tested from 7% to 12% compared with amphotericin B alone at therapeutic concentrations. Furthermore, the addition of vitamin C and vitamin E protects human red blood cells against the cytotoxicity induced by amphotericin B with 17%. This is due may be to the antioxidant power of vitamins which confer protection against the autoxidation of the molecule of amphotericin B. On the other hand, it is noticed that the yeast regrows after 24h whatever in complex with vitamin C or vitamin E of the stock solution. On completion of this study, the incorporation of antioxidant vitamins that we propose to the reaction medium of antifungal improved the therapeutic index of amphotericin B. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

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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.

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

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Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

2018-03-01

Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

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

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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

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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

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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 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.

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

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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.

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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.

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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.

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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 ...

Self-Efficacy Manipulation Influences Physical Activity Enjoyment in Chinese Adolescents.

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Hu, Liang; Cheng, Shoubin; Lu, Jiaying; Zhu, Lele; Chen, Ling

2016-02-01

In this study, we examined the effect of the manipulation of exercise self-efficacy on the enjoyment of physical activity in a sample of 44 Chinese adolescents (age = 14.27 ± .87 y), including 22 boys and 22 girls. The participants were randomized into a low-efficacy or high-efficacy condition, and their self-efficacy beliefs for engaging in moderate-intensity physical activity were manipulated by providing false feedback after a submaximal exercise test. The participants' self-efficacy was measured and compared before and after the exercise test and the participants' enjoyment of physical activity was assessed after the exercise test. It was found that exercise self-efficacy was successfully manipulated in the expected direction in both conditions, which significantly influenced the participants' enjoyment of physical activity. After the exercise test, the participants in the low-efficacy condition reported lower enjoyment scores relative to the high-efficacy participants. These results suggest that self-efficacy may have an important influence on the enjoyment of physical activity among Chinese adolescents. We recommend that physical activity promotion programs should be tailored to enhance adolescents' self-efficacy beliefs and enjoyment of the experience of physical activity.

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

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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.

Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

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Greenbaum, Carla J; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M; Kolb, Hubert

2008-10-01

Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

Microneedle physical contact as a therapeutic for abnormal scars.

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Yeo, David C; Balmayor, Elizabeth R; Schantz, Jan-Thorsten; Xu, Chenjie

2017-08-14

Abnormal (keloid and hypertrophic) scars are a significant affliction with no satisfactory single modality therapy to-date. Available options are often ineffective, painful, potentially hazardous, and require healthcare personnel involvement. Herein a self-administered microneedle device based on drug-free physical contact for inhibiting abnormal scars is reported. Its therapeutic activity through microneedle contact eliminates hazards associated with toxic anti-scarring drugs while self-treatment enables administration flexibility. The microneedle patch was fabricated with FDA-approved liquid crystalline polymer under good manufacturing practice. It was first tested to ascertain its ability to inhibit (keloid) fibroblast proliferation. Later the microneedle patch was examined on the rabbit ear hypertrophic scar model to explore its potential in inhibiting the generation of abnormal scars post-injury. Finally, the microneedle patch was applied to the caudal region of a hypertrophic scar located on a female patient's dorsum to verify clinical efficacy. On untreated control cultures, barely any non-viable fibroblasts could be seen. After 12-h treatment with the microneedle patch, the non-viable proportion increased to 83.8 ± 11.96%. In rabbit ear hypertrophic scar model, 100% of the control wounds without the presence of patches on rabbit ears generated regions of raised dermis originating from the wound site (3/3), whereas microneedle treatment prevented dermis tissue thickening in 83.33% of the wounds (15/18). In the clinical test, the microneedle patch was well tolerated by the patient. Compared to the untreated region, microneedle treatment decreased the number of infiltrated inflammatory cells, with less disrupted dermis tissue architecture and more flattened appearance. A self-administered, drug-free microneedle patch appears highly promising in reducing abnormal scarring as observed from in vitro, in vivo and clinical experiments. Larger cohort clinical

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

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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.

[Safety and efficacy of a new preservative-free levocabastine ophthalmic solution (Levofree®) using the conjunctival provocation test].

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Allaire, C; Siou-Mermet, R; Bassols, A

2012-09-01

To evaluate the safety and efficacy of preservative-free levocabastine 0.05 % ophthalmic solution compared to placebo (vehicle) and to preserved levocabastine 0.05 % ophthalmic suspension in the prevention of allergic conjunctivitis induced by a conjunctival provocation test. Ninety-two subjects (18-50 years) with a previous history of allergic conjunctivitis to pollen were randomised to receive either preservative-free levocabastine solution in one eye and preserved levocabastine suspension in the fellow eye (n=69), or preservative-free levocabastine in one eye and placebo in the fellow eye (n=23). One drop of each product was administered 10 minutes (visit 3) and 4 hours (visit 4) prior to the provocation test. The primary efficacy criterion was the sum of the itching and conjunctival hyperemia scores assessed at 3, 5 and 10 minutes after the provocation test. The safety evaluation included adverse events, visual acuity, intra-ocular pressure and study drug drop sensation. The efficacy of the preservative-free solution was significantly higher than that of placebo at all time points (P≤0.01) with one exception at visit 4 (3 minutes after the provocation test). It was significantly higher than that of the preserved suspension at visit 3, and equivalent at visit 4. The incidence of adverse events was lower with the preservative-free solution than with the preserved suspension. 94.2 % and 95.7 % subjects rated preservative-free levocabastine drop sensation as "good" or "very good" at visits 3 and 4 respectively, whereas these rates were 68.1 % and 63.8 % with preserved levocabastine. This difference between the two formulations was highly statistically significant (Ppreservative-free levocabastine was superior to that of the placebo and of the preserved suspension at visit 3, at least as effective as the preserved suspension at visit 4, and better tolerated at each visit. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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

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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.

Therapeutic efficacy of nonsteroidal anti-inflammatory drug therapy versus exercise therapy in patients with chronic nonspecific low back pain: a prospective study.

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Takahashi, Naoto; Omata, Jun-Ichi; Iwabuchi, Masumi; Fukuda, Hironari; Shirado, Osamu

2017-04-28

Therapy for chronic, nonspecific low back pain is mainly conservative: medication and/or exercise.　Pharmacotherapy, however, has side effects, and the quantities of concomitant drugs in older persons require attention.　Although exercise promises improved function, its use to alleviate pain is controversial.　Thus, we compared the efficacy of pharmacotherapy versus exercise for treating chronic nonspecific low back pain.　The pharmacotherapy group (n=18: 8 men, 10 women) were prescribed celecoxib monotherapy.　The exercise group (n=22: 10 men, 12 women) undertook stretching exercises.　Because of drop-outs, the NSAID group (n=15: 7 men, 8 women) and the exercise group (n =18: 8 men, 10 women) were finally analyzed.　We applied a visual analog scale, Roland-Morris disability scores, and the 36-Item Short Form Health Survey.　We used a paired t-test for within-group analyses and an unpaired t-test for between-group analyses.　Pain relief was achieved after 3 months of pharmacotherapy or exercise.　Quality of life improved only in the exercise group.　Recovery outcomes for the two groups were not significantly different.　Efficacy of exercise therapy for strictly defined low back pain was almost equivalent to that of pharmacotherapy and provided better quality of life.

The Relationship Between Advertising-Induced Anger and Self-efficacy on Persuasive Outcomes: A Test of the Anger Activism Model Using the Truth Campaign.

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Ilakkuvan, Vinu; Turner, Monique Mitchell; Cantrell, Jennifer; Hair, Elizabeth; Vallone, Donna

Turner's Anger Activism Model (AAM) contends anger and efficacy interact in a unique way to determine message responses to campaign materials. This study tested the AAM using responses to 2 truth antismoking advertisements collected in August-October 2014 via an online, cross-sectional survey of 15- to 21-year-olds. Those aware of each of the truth advertisements (n = 319 for each) were organized into 4 anger/efficacy groups. Analysis of variance and regressions were conducted to understand group differences in message-related cognitions (persuasiveness, receptivity, conversation). Message cognitions were highest among the high anger/high efficacy group and lowest among the low anger/low efficacy group.

Efficacy of Topical Therapy with Newly Developed Terbinafine and Econazole Formulations in the Treatment of Dermatophytosis in Cats.

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Ivaskiene, M; Matusevicius, A P; Grigonis, A; Zamokas, G; Babickaite, L

2016-09-01

In the field of veterinary dermatology dermatophytosis is one of the most frequently occurring infectious diseases, therefore its treatment should be effective, convenient, safe and inexpensive. The aim of this study was to evaluate the efficacy of newly developed topical formulations in the treatment of cats with dermatophytosis. Evaluation of clinical efficacy and safety of terbinafine and econazole formulations administered topically twice a day was performed in 40 cats. Cats, suffering from the most widely spread Microsporum canis-induced dermatophytosis and treated with terbinafine hydrochloride 1% cream, recovered within 20.3±0.88 days; whereas when treated with econazole nitrate 1% cream, they recovered within 28.4±1.14 days. A positive therapeutic effect was yielded by combined treatment with local application of creams and whole coat spray with enilconazole 0.2% emulsion "Imaverol". Most cats treated with econazole cream revealed redness and irritation of the skin at the site of application. This study demonstrates that terbinafine tended to have superior clinical efficacy (p<0.001) in the treatment of dermatophytosis in cats compared to the azole tested.

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

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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

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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.

Histatin 5-spermidine conjugates have enhanced fungicidal activity and efficacy as a topical therapeutic for oral candidiasis.

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Tati, Swetha; Li, Rui; Puri, Sumant; Kumar, Rohitashw; Davidow, Peter; Edgerton, Mira

2014-01-01

Oropharyngeal candidiasis (OPC) is caused by the opportunistic fungi Candida albicans and is prevalent in immunocompromised patients, individuals with dry mouth, or patients with prolonged antibiotic therapies that reduce oral commensal bacteria. Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. However, Hsts are rapidly degraded in vivo, limiting their usefulness as therapeutic agents despite their lack of toxicity. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54-15), based upon our findings that C. albicans spermidine transporters are required for Hst 5 uptake and fungicidal activity. We found that Hst 54-15-Spd was significantly more effective in killing C. albicans and Candida glabrata than Hst 5 alone in both planktonic and biofilm growth and that Hst 54-15-Spd retained high activity in both serum and saliva. Hst 54-15-Spd was not bactericidal against streptococcal oral commensal bacteria and had no hemolytic activity. We tested the effectiveness of Hst 54-15-Spd in vivo by topical application to tongue surfaces of immunocompromised mice with OPC. Mice treated with Hst 54-15-Spd had significant clearance of candidal tongue lesions macroscopically, which was confirmed by a 3- to 5-log fold reduction of C. albicans colonies recovered from tongue tissues. Hst 54-15-Spd conjugates are a new class of peptide-based drugs with high selectivity for fungi and potential as topical therapeutic agents for oral candidiasis.

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

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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.

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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?

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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)

Is Huachansu Beneficial in Treating Advanced Non-Small-Cell Lung Cancer? Evidence from a Meta-Analysis of Its Efficacy Combined with Chemotherapy

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Bingduo Zhou

2015-01-01

Full Text Available Background. Huachansu, the sterilized water extract of Bufo bufo gargarizans toad skin, is used in China to alleviate the side-effects and enhance the therapeutic effect of chemotherapy in advanced non-small-cell lung cancer (NSCLC. We conducted a meta-analysis to assess Huachansu’s efficacy. Methods. We extensively searched electronic databases (CENTRAL, EMBASE, MEDLINE, CBM, Cochrane Library, CNKI, CEBM, WFDP, CSCD, CSTD, and IPA for randomized controlled trials containing Huachansu plus chemotherapy as the test group and chemotherapy as the control group. Seventeen trials were selected based on the selection criteria. The pooled relative ratio (RR of indicators with 95% confidence interval (95% CI was calculated for efficacy evaluation. Results. The meta-analysis demonstrated a statistically significant improvement in objective tumor response, one-year survival, Karnofsky performance status, pain relief, and alleviation of severe side-effects (nausea and vomiting, leukocytopenia in the test group as compared to the control group, but no significant difference in thrombocytopenia. Conclusions. This study demonstrated the efficacy of Huachansu combined with chemotherapy in the treatment of advanced NSCLC. However, limitations exist and high-quality trials are needed for further verification.

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

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Jan B W J Cornelissen

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

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

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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.

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

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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

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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

Treatment Model in Children with Speech Disorders and Its Therapeutic Efficiency

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Barberena, Luciana

2014-05-01

Full Text Available Introduction Speech articulation disorders affect the intelligibility of speech. Studies on therapeutic models show the effectiveness of the communication treatment. Objective To analyze the progress achieved by treatment with the ABAB—Withdrawal and Multiple Probes Model in children with different degrees of phonological disorders. Methods The diagnosis of speech articulation disorder was determined by speech and hearing evaluation and complementary tests. The subjects of this research were eight children, with the average age of 5:5. The children were distributed into four groups according to the degrees of the phonological disorders, based on the percentage of correct consonants, as follows: severe, moderate to severe, mild to moderate, and mild. The phonological treatment applied was the ABAB—Withdrawal and Multiple Probes Model. The development of the therapy by generalization was observed through the comparison between the two analyses: contrastive and distinctive features at the moment of evaluation and reevaluation. Results The following types of generalization were found: to the items not used in the treatment (other words, to another position in the word, within a sound class, to other classes of sounds, and to another syllable structure. Conclusion The different types of generalization studied showed the expansion of production and proper use of therapy-trained targets in other contexts or untrained environments. Therefore, the analysis of the generalizations proved to be an important criterion to measure the therapeutic efficacy.

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

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Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

2017-01-01

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

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

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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.

The Effect of Time-Management Training on Test-Anxiety and Self-Efficacy of Iranian Intermediate EFL Learners

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Behnam, Biook; Jenani, Shalaleh; Ahangari, Saeideh

2014-01-01

The present study aimed to examine the effect of time-management training on Iranian EFL learners' test-anxiety and self-efficacy. A quasi-experimental design was used. The study was carried out in Tabriz Azad University and University of Applied Sciences and Technology. Thirty-eight BA students majoring in TEFL who enrolled in the above mentioned…

Weakened Resilience in Parenting Self-Efficacy in Pregnant Women Who Were Abused in Childhood: An Experimental Test.

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Florentina C Kunseler

Full Text Available This study tested experimentally whether the combination of a history of childhood abuse and confrontation with difficult infant temperament is associated with negative changes in parenting self-efficacy. First-time pregnant women (N = 243 participated in the Adult Attachment Interview, which was used to assess the occurrence of abuse by parents in childhood and unresolved representations, and completed a task asking them to respond to infant cries. Sixty of the 243 participants (25% experienced childhood abuse, mostly physical or sexual. The task simulated infant temperamental difficulty by manipulating soothing success in order to reflect an easy-to-soothe (80% soothing success and a difficult-to-soothe infant (20% soothing success. Both after baseline and after each of the two stimulus series women assessed their parenting self-efficacy. Women who reported childhood abuse did not differ from women who reported no childhood abuse in parenting self-efficacy at baseline or in response to the easy-to-soothe infant (relative to baseline, but decreased more in parenting self-efficacy following the difficult-to-soothe infant. Effects did not vary according to resolution of trauma. These findings suggest that in response to infant temperamental difficulty, women who experienced childhood abuse may more easily lose confidence in their parenting abilities, which underlines the importance of preparing at-risk women for the possible challenges that come along with parenthood.

Situated Self-efficacy in Introductory Physics Students

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Henderson, Rachel; DeVore, Seth; Michaluk, Lynnette; Stewart, John

2017-01-01

Within the general university environment, students' perceived self-efficacy has been widely studied and findings suggest it plays a role in student success. The current research adapted a self-efficacy survey, from the ``Self-Efficacy for Learning Performance'' subscale of the Motivated Learning Strategies Questionnaire and administered it to the introductory, calculus-based physics classes (N=1005) over the fall 2015 and spring 2016 semesters. This assessment measured students' self-efficacy in domains including the physics class, other science and mathematics classes, and their intended future career. The effect of gender was explored with the only significant gender difference (p gender difference was not explained by a student's performance which was measured by test average. However, a mediation analysis showed that students' overall academic self-efficacy, measured by their math and science self-efficacy, acts as a mediator for the effect of test average on self-efficacy towards the physics class domain. This mediation effect was significant for both female (p < . 01) and male students (p < . 001) however, it was more pronounced for male students.

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

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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

Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

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Greenbaum, Carla J.; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M.; Kolb, Hubert

2008-01-01

OBJECTIVE—β-Cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS—In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS—Among individuals with up to 4 years’ duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R2 = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS—The MMTT is preferred for the assessment of β-cell function in therapeutic trials in type 1 diabetes. PMID:18628574

Utilization of diagnostic ultrasound and intravenous lipid-encapsulated perfluorocarbons in non-invasive targeted cardiovascular therapeutics.

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Porter, Thomas R; Choudhury, Songita A; Xie, Feng

2016-01-01

Diagnostic ultrasound (DUS) pressures have the ability to induce inertial cavitation (IC) of systemically administered microbubbles; this bioeffect has many diagnostic and therapeutic implications in cardiovascular care. Diagnostically, commercially available lipid-encapsulated perfluorocarbons (LEP) can be utilized to improve endocardial and vascular border delineation as well as assess myocardial perfusion. Therapeutically, the liquid jets induced by IC can alter endothelial function and dissolve thrombi within the immediate vicinity of the cavitating microbubbles. The cavitating LEP can also result in the localized release of any bound therapeutic substance at the site of insonation. DUS-induced IC has been tested in pre-clinical studies to determine what effect it has on acute vascular and microvascular thrombosis as well as nitric oxide (NO) release. These pre-clinical studies have consistently shown that DUS-induced IC of LEP is effective in restoring coronary vascular and microvascular flow in acute ST segment elevation myocardial infarction (STEMI), with microvascular flow improving even if upstream large vessel flow has not been achieved. The initial clinical trials examining the efficacy of short pulse duration DUS high mechanical index impulses in patients with STEMI are underway, and preliminary studies have suggested that earlier epicardial vessel recanalization can be achieved prior to arriving in the cardiac catheterization laboratory. DUS high mechanical index impulses have also been effective in pre-clinical studies for targeting DNA delivery that has restored islet cell function in type I diabetes and restored vascular flow in the extremities downstream from a peripheral vascular occlusion. Improvements in this technique will come from three dimensional arrays for therapeutic applications, more automated delivery techniques that can be applied in the field, and use of submicron-sized acoustically activated LEP droplets that may better permeate the

Therapeutic efficacy of traditional Chinese medicine, Shen-Mai San, in cancer patients undergoing chemotherapy or radiotherapy: study protocol for a randomized, double-blind, placebo-controlled trial

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Lo Lun-Chien

2012-12-01

Full Text Available Abstract Background Cancer is one of the major health issues worldwide. An increasing number of cancer patients are offered treatment with surgery, chemotherapy and radiotherapy. Traditional Chinese medicine (TCM is one of the most common complementary therapies offered to cancer patients in Taiwan. We designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of TCM in patients with cancer. Methods/design In this study, inclusion criteria are postoperative patients with histologically confirmed cancer within 3 years who are undergoing chemotherapy or radiotherapy, more than 18 years old, have given signed informed consent, have the ability to read Chinese, and the ability for oral intake. Exclusion criteria include being pregnant, breast feeding, having completed chemotherapy or radiotherapy, brain metastasis with Eastern Cooperative Oncology Group (ECOG performance status of two to four, delusion or hallucinations, acute infection, and have received medications under other clinical trials. The patients were separated into an intervention group (Shen-Mai-San, SMS and a placebo group for four weeks using a randomized, double-blind procedure. The European Organization for Research and Treatment of Cancer (EORTC Quality of Life questionnaire (QOL-C30 was used to evaluate the quality of life. General data, hemoglobin (Hb, hematocrit (Hct, glutamic-oxalacetic transaminase (GOT, glutamic-pyruvic transaminase (GPT, blood urea nitrogen (BUN, creatinine, carcinoembryonic antigen (CEA, TCM diagnosis data and heart rate variability (HRV were also recorded. These data were collected at baseline, two weeks and four weeks after receiving medication. The patients were prescribed granules which contained therapeutic medicines or placebo. Paired-T test was used for statistical analysis. Discussion Shen-Mai-San is composed of processed Ginseng radis, Liriope spicata, and Schizandrae fructus. It was found to be effective for

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

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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

Is the efficacy of antidepressants in panic disorder mediated by adverse events? A mediational analysis.

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Irene Bighelli

Full Text Available It has been hypothesised that the perception of adverse events in placebo-controlled antidepressant clinical trials may induce patients to conclude that they have been randomized to the active arm of the trial, leading to the breaking of blind. This may enhance the expectancies for improvement and the therapeutic response. The main objective of this study is to test the hypothesis that the efficacy of antidepressants in panic disorder is mediated by the perception of adverse events. The present analysis is based on a systematic review of published and unpublished randomised trials comparing antidepressants with placebo for panic disorder. The Baron and Kenny approach was applied to investigate the mediational role of adverse events in the relationship between antidepressants treatment and efficacy. Fourteen placebo-controlled antidepressants trials were included in the analysis. We found that: (a antidepressants treatment was significantly associated with better treatment response (ß = 0.127, 95% CI 0.04 to 0.21, p = 0.003; (b antidepressants treatment was not associated with adverse events (ß = 0.094, 95% CI -0.05 to 0.24, p = 0.221; (c adverse events were negatively associated with treatment response (ß = 0.035, 95% CI -0.06 to -0.05, p = 0.022. Finally, after adjustment for adverse events, the relationship between antidepressants treatment and treatment response remained statistically significant (ß = 0.122, 95% CI 0.01 to 0.23, p = 0.039. These findings do not support the hypothesis that the perception of adverse events in placebo-controlled antidepressant clinical trials may lead to the breaking of blind and to an artificial inflation of the efficacy measures. Based on these results, we argue that the moderate therapeutic effect of antidepressants in individuals with panic disorder is not an artefact, therefore reflecting a genuine effect that doctors can expect to replicate under real-world conditions.

Safety and efficacy of Regadenoson in myocardial perfusion imaging (MPI) stress tests: A review

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Ahmed, Ambereen

2018-02-01

Myocardial perfusion imaging (MPI) tests are often used to help diagnose coronary heart disease (CAD). The tests usually involve applying stress, such as hard physical exercise together with administration of vasodilators, to the patients. To date, many of these tests use non-selective A2A adenosine receptor agonists which, however, can be associated with highly undesirable and life-threatening side effects such as chest pain, dyspnea, severe bronchoconstriction and atrioventricular conduction anomalies. Regadenoson is a relatively new, highly selective A2A adenosine receptor agonist, suitable for use in MPI tests which exhibits far fewer adverse side effects and, unlike others testing agents, can be used without the necessity of excessive concomitant exercise. Also, the dose of regadenoson required is not dependent upon patient weight or renal impairment, and it can be rapidly administered by i.v. Injection. Regadenoson use in MPI testing thus has the potential as a simplified, relatively safe, time-saving and cost-effective method for helping diagnose CAD. The present study was designed to review several articles on the safety, efficacy, and suitability of regadenoson in MPI testing for CAD. Overall, the combined studies demonstrated that use of regadenoson in conjunction with low-level exercise in MPI is a highly efficient and relatively safe test for CAD, especially for more severe health-compromised patients.

Nanoparticle delivery of chemosensitizers improve chemotherapy efficacy without incurring additional toxicity

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Caster, Joseph M.; Sethi, Manish; Kowalczyk, Sonya; Wang, Edina; Tian, Xi; Nabeel Hyder, Sayed; Wagner, Kyle T.; Zhang, Ying-Ao; Kapadia, Chintan; Man Au, Kin; Wang, Andrew Z.

2015-01-01

Chemosensitizers can improve the therapeutic index of chemotherapy and overcome treatment resistance. Successful translation of chemosensitizers depends on the development of strategies that can preferentially deliver chemosensitizers to tumors while avoiding normal tissue. We hypothesized that nanoparticle (NP) formulation of chemosensitizers can improve their delivery to tumors which can in turn improve their therapeutic index. To demonstrate the proof of principle of this approach, we engineered NP formulations of two chemosensitizers, the PI3-kindase inhibitor wortmanin (Wtmn) and the PARP inhibitor olaparib. NP Wtmn and NP olaparib were evaluated as chemosensitizers using lung cancer cells and breast cancer cells respectively. We found Wtmn to be an efficient chemosensitizer in all tested lung-cancer cell lines reducing tumor cell growth between 20 and 60% compared to drug alone. NP formulation did not decrease its efficacy in vitro. Olaparib showed less consistent chemosensitization as a free drug or in NP formulation. NP Wtmn was further evaluated as a chemosensitizer using mouse models of lung cancer. We found that NP Wtmn is an effective chemosensitizer and more effective than free Wtmn showing a 32% reduction in tumor growth compared to free Wtmn when given with etoposide. Importantly, NP Wtmn was able to sensitize the multi-drug resistant H69AR cells to etoposide. Additionally, the combination of NP Wtmn and etoposide chemotherapy did not significantly increase toxicity. The present study demonstrates the proof of principle of using NP formulation of chemosensitizing drugs to improve the therapeutic index of chemotherapy.

Anticedents to entrepreneurial intentions: Testing for measurement invariance for cultural values, attitudes and self-efficacy beliefs across ethnic groups

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Boris Urban

2008-10-01

Full Text Available Building on previous research on antecedents of entrepreneurial intentions, various measures were tested across different ethnic groups in South Africa. Factorial homogeneity is an important attribute for any scale intended for use in multicultural research, and since tests of equivalency are not routinely applied, this article hypothesised measurement invariance across ethnic groups. Theoretical discussions on Hofstede’s (2001 value survey module (VSM 94, attitudes towards and beliefs about entrepreneurial intentions, general self-efficacy (GSE, and entrepreneurial self-efficacy (ESE preceded the use of statistical analysis. Confirmatory factor analysis based on 210 respondents indicated that equivalence for the underlying factors across the different ethnic groups could not be established, and that the three groups demonstrated different underlying structures. In conclusion, stereotypic declarations of an integrated South African culture were not supported by this research in terms of entrepreneurial intentions and their antecedents.

Oncolytic Viruses: Therapeutics With an Identity Crisis

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Caroline J. Breitbach

2016-07-01

Full Text Available Oncolytic viruses (OV are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a “one-size fits all” approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.

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

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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

Applicability of an exaggerated forearm wash test for efficacy testing of two corticosteroids, tacrolimus and glycerol, in topical formulations against skin irritation induced by two different irritants

DEFF Research Database (Denmark)

Clemmensen, A; Andersen, F; Petersen, T K

2011-01-01

applied, we tested the efficacy of four anti-irritant compounds using the two different irritants sodium lauryl sulfate (SLS) and nonanoic acid (NON). Methods: In a randomized, double-blind, controlled trial, healthy volunteers were exposed to 5% SLS and 50% NON (the right and the left forearm...

The immunological potency and therapeutic potential of a prototype dual vaccine against influenza and Alzheimer's disease

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Martinez-Sobrido Luis

2011-08-01

Full Text Available Abstract Background Numerous pre-clinical studies and clinical trials demonstrated that induction of antibodies to the β-amyloid peptide of 42 residues (Aβ42 elicits therapeutic effects in Alzheimer's disease (AD. However, an active vaccination strategy based on full length Aβ42 is currently hampered by elicitation of T cell pathological autoreactivity. We attempt to improve vaccine efficacy by creating a novel chimeric flu vaccine expressing the small immunodominant B cell epitope of Aβ42. We hypothesized that in elderly people with pre-existing memory Th cells specific to influenza this dual vaccine will simultaneously boost anti-influenza immunity and induce production of therapeutically active anti-Aβ antibodies. Methods Plasmid-based reverse genetics system was used for the rescue of recombinant influenza virus containing immunodominant B cell epitopes of Aβ42 (Aβ1-7/10. Results Two chimeric flu viruses expressing either 7 or 10 aa of Aβ42 (flu-Aβ1-7 or flu-Aβ1-10 were generated and tested in mice as conventional inactivated vaccines. We demonstrated that this dual vaccine induced therapeutically potent anti-Aβ antibodies and anti-influenza antibodies in mice. Conclusion We suggest that this strategy might be beneficial for treatment of AD patients as well as for prevention of development of AD pathology in pre-symptomatic individuals while concurrently boosting immunity against influenza.

Two in-vivo protocols for testing virucidal efficacy of handwashing and hand disinfection.

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Steinmann, J; Nehrkorn, R; Meyer, A; Becker, K

1995-01-01

Whole-hands and fingerpads of seven volunteers were contaminated with poliovirus type 1 Sabin strain in order to evaluate virucidal efficacy of different forms of handwashing and handrub with alcohols and alcohol-based disinfectants. In the whole-hand protocol, handwashing with unmedicated soap for 5 min and handrubbing with 80% ethanol yielded a log reduction factor (RF) of > 2, whereas the log RF by 96.8% ethanol exceeded 3.2. With the fingerpad model ethanol produced a greater log RF than iso- or n-propanol. Comparing five commercial hand disinfectants and a chlorine solution (1.0% chloramine T-solution) for handrub, Desderman and Promanum, both composed of ethanol, yielded log RFs of 2.47 and 2.26 respectively after an application time of 60 s, similar to 1.0% chloramine T-solution (log RF of 2.28). Autosept, Mucasept, and Sterillium, based on n-propanol and/or isopropanol, were found to be significantly less effective (log RFs of 1.16, 1.06 and 1.52 respectively). A comparison of a modified whole-hand and the fingerpad protocol with Promanum showed similar results with the two systems suggesting both models are suitable for testing the in-vivo efficacy of handwashing agents and hand disinfectants which are used without any water.

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

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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

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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

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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...

A Technology Platform to Test the Efficacy of Purification of Alginate

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Genaro A. Paredes-Juarez

2014-03-01

Full Text Available Alginates are widely used in tissue engineering technologies, e.g., in cell encapsulation, in drug delivery and various immobilization procedures. The success rates of these studies are highly variable due to different degrees of tissue response. A cause for this variation in success is, among other factors, its content of inflammatory components. There is an urgent need for a technology to test the inflammatory capacity of alginates. Recently, it has been shown that pathogen-associated molecular patterns (PAMPs in alginate are potent immunostimulatories. In this article, we present the design and evaluation of a technology platform to assess (i the immunostimulatory capacity of alginate or its contaminants, (ii where in the purification process PAMPs are removed, and (iii which Toll-like receptors (TLRs and ligands are involved. A THP1 cell-line expressing pattern recognition receptors (PRRs and the co-signaling molecules CD14 and MD2 was used to assess immune activation of alginates during the different steps of purification of alginate. To determine if this activation was mediated by TLRs, a THP1-defMyD88 cell-line was applied. This cell-line possesses a non-functional MyD88 coupling protein, necessary for activating NF-κB via TLRs. To identify the specific TLRs being activated by the PAMPs, we use different human embryonic kidney (HEK cell-line that expresses only one specific TLR. Finally, specific enzyme-linked immunosorbent assays (ELISAs were applied to identify the specific PAMP. By applying this three-step procedure, we can screen alginate in a manner, which is both labor and cost efficient. The efficacy of the platform was evaluated with an alginate that did not pass our quality control. We demonstrate that this alginate was immunostimulatory, even after purification due to reintroduction of the TLR5 activating flagellin. In addition, we tested two commercially available purified alginates. Our experiments show that these commercial

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

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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.

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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.

Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

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Ju, Jingfang

2018-01-01

Background Resistance to 5-Fluorouracil (5-FU) based chemotherapy is the major reason for failure of treating patients with advanced colorectal cancer. Materials and methods In this study, we developed a novel miR-129 mimic with potent efficacy in eliminating resistant colon cancer stem cells both in vitro and in vivo. We integrated 5-FU into miR-129 by replacing Uracil (U) to generate 5-FU-miR-129 mimics (Mimic-1). Results Mimic-1 is a strong therapeutic candidate with a number of unique features. Mimic-1 can be delivered to cancer cells without any transfection reagents (e.g. lipids, viral vector, nanoparticles). Mimic-1 is more potent at inhibiting cell proliferation and inducing cell cycle arrest at G1 phase than native miR-129 and the other mimics tested, while retaining target specificity. Mimic-1 prevents colon cancer metastasis in vivo without toxicity. Conclusion This represents a significant advancement in the development of a nontoxic and highly potent miRNA based cancer therapeutics and establishes a foundation for further developing Mimic-1 as a novel anti-cancer therapeutic for treating colorectal cancer. PMID:29507661

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

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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.

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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.

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

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.

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

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...

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

Science.gov (United States)

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.

RNA interference-based therapeutics: new strategies to fight infectious disease.

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López-Fraga, M; Wright, N; Jiménez, A

2008-12-01

For many years, there has been an ongoing search for new compounds that can selectively alter gene expression as a new way to treat human disease by addressing targets that are otherwise "undruggable" with traditional pharmaceutical approaches involving small molecules or proteins. RNA interference (RNAi) strategies have raised a lot of attention and several compounds are currently being tested in clinical trials. Viruses are the obvious target for RNAi-therapy, as most are difficult to treat with conventional drugs, they become rapidly resistant to drug treatment and their genes differ substantially from human genes, minimizing side effects. Antisense strategy offers very high target specificity, i.e., any viral sequence could potentially be targeted using the complementary oligonucleotide sequence. Consequently, new antisense-based therapeutics have the potential to lead a revolution in the anti-infective drug development field. Additionally, the relatively short turnaround for efficacy testing of potential RNAi molecules and that any pathogen is theoretically amenable to rapid targeting, make them invaluable tools for treating a wide range of diseases. This review will focus on some of the current efforts to treat infectious disease with RNAi-based therapies and some of the obstacles that have appeared on the road to successful clinical intervention.

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

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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.

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

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Vij, Neeraj

2011-09-01

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are 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 hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

Efficacy of 131I treatment for 840 cases of Graves' disease combined with hepatic function injury

International Nuclear Information System (INIS)

Yin Liang; Tan Jian; Wang Renfei

2012-01-01

Objective: To assess the efficacy of 131 I treatment for Graves' disease (GD) complicated with hepatic function injury in order to provide guidance for clinical practice. Methods: A total of 840 GD cases complicated with hepatic function injury were retrospectively reviewed after 131 I treatment. Analysis of variance and Dunnett t test were used to compare serum FT 3 , FT 4 , and TSH levels before and 1, 3, and 6 months after 131 I therapy. R × C table χ 2 test was used to compare therapeutic efficacies among cases with different degrees and types of hepatic function injuries. Analysis of variance and Dunnett t test were used to evaluate recovery time of different degrees of hepatic function injuries. Cross classification 2 × 2 table correlation analysis was adopted to assess the correlation between 131 I therapeutic efficacies of GD and recovery efficacies of hepatic function. Results: The curative rate for GD was 76.8% (645/840). There were significant changes of FT 3 ((25.74 ± 5.81), (15.54 ± 4.12), (12.76 ± 2.35) and (7.95 ± 1.64) pmol/L, respectively; F=5007.958, t=54.455, 69.297 and 94.976, all P<0.05), FT 4 ((75.84 ± 16.78), (45.69 ±8.96), (36.81 ± 5.03) and (25.17 ±.4.46) pmol/L, respectively; F=3876.410, t=513.602, 664.871 and 863.157, all P<0.05) and TSH ((0.01 ±0.02), (0.02±0.08), (0.85 ±0.36) and (1.26 ± 0.54) mU/L, respectively; F=3050.430, t=2.627, 46.989 and 78.315, all P<0.05) before and 1,3,and 6 months after 131 I treatment. The curative rate of hepatic function abnormality was 79.2% (665/840). For mild, medium and severe hepatic function injury patients, curative rates were 88.4% (420/475), 68.8% (214/311) and 57.4% (31/54), respectively. The curative rate of patients with mild hepatic function injury was significantly higher than those with medium and severe hepatic function injury (χ 2 =46.338, 37.100, respectively, both P<0.01), and the recovery time was significantly shorter in patients with mild hepatic function injury

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)

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

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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.

Teachers’ work ability: a study of relationships between collective efficacy and self-efficacy beliefs

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Guidetti G

2018-05-01

Full Text Available Gloria Guidetti,1 Sara Viotti,1 Andreina Bruno,2 Daniela Converso1 1Department of Psychology, University of Turin, Turin, Italy; 2Department of Education Science, University of Genoa, Genoa, Italy Introduction: Work ability constitutes one of the most studied well-being indicators related to work. Past research highlighted the relationship with work-related resources and demands, and personal resources. However, no studies highlight the role of collective and self-efficacy beliefs in sustaining work ability. Purpose: The purpose of this study was to examine whether and by which mechanism work ability is linked with individual and collective efficacies in a sample of primary and middle school teachers. Materials and methods: Using a dataset consisting of 415 primary and middle school Italian teachers, the analysis tested for the mediating role of self-efficacy between collective efficacy and work ability. Results: Mediational analysis highlights that teachers’ self-efficacy totally mediates the relationship between collective efficacy and perceived work ability. Conclusion: Results of this study enhance the theoretical knowledge and empirical evidence regarding the link between teachers’ collective efficacy and self-efficacy, giving further emphasis to the concept of collective efficacy in school contexts. Moreover, the results contribute to the study of well-being in the teaching profession, highlighting a process that sustains and promotes levels of work ability through both collective and personal resources. Keywords: collective efficacy, mediation, self-efficacy, teachers, work ability

Therapeutic abortion follow-up study.

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Margolis, A J; Davison, L A; Hanson, K H; Loos, S A; Mikkelsen, C M

1971-05-15

To determine the long-range psychological effects of therapeutic abortion, 50 women (aged from 13-44 years), who were granted abortions between 1967 and 1968 Because of possible impairment of mental and/or physical health, were analyzed by use of demographic questionnaires, psychological tests, and interviews. Testing revealed that 44 women had psychiatric problems at time of abortion. 43 patients were followed for 3-6 months. The follow-up interviews revealed that 29 patients reacted positively after abortion, 10 reported no significant change and 4 reacted negatively. 37 would definitely repeat the abortion. Women under 21 years of age felt substantially more ambivalent and guilty than older patients. A study of 36 paired pre- and post-abortion profiles showed that 15 initially abnormal tests had become normal. There was a significant increase in contraceptive use among the patients after the abortion, but 4 again became pregnant and 8 were apparently without consistent contraception. It is concluded that the abortions were therapeutic, but physicians are encouraged to be aware of psychological problems in abortion cases. Strong psychological and contraceptive counselling should be exercised.

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.

EFFICACY EVALUATION OF A MONOCLONAL ANTIBODY AGAINST THE EPIDERMAL GROWTH FACTORS RECEPTOR IN THE MODEL OF SUBCUTANEOUS XENOGRAFT IN IMMUNODEFICIENT MICE

Directory of Open Access Journals (Sweden)

Ya. Yu. Ustyugov

2015-01-01

Full Text Available This article presents the results of the comparative antitumor efficacy study of two test articles of therapeutic humanized monoclonal antibodies against epidermal growth factor receptor (EGFR manufactured by Russian biopharmaceutical company CJSC “Biocad” and the commercial drug “Erbitux®” (Merck, Germany in subcutaneous xenografts model using human epidermoid carcinoma A431NS cell line. EGFR overexpression in epithelial tumor cells is a commonly known fact that determines use of this receptor as a target for therapeutic monoclonal antibodies. The basic mechanism of action of such drugs is blocking of epithelial cells proliferation through competitive binding to EGFR. Evaluation of tumor growth dynamics in immunodeficient (Nu/Nu mice was performed during in vivo experiment using two parameters: tumor growth index and tumor growth inhibition (TGI, %. The results received with used study design show that antitumor effects of the test articles manufactured by CJSC “Biocad” and the commercial comparator drug “Erbitux®” estimated by values of TGI and tumor growth index are comparable.

Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects.

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Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

2016-09-20

To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

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.

No benefit of therapeutic vaccination in clinically healthy cats persistently infected with feline leukemia virus.

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Helfer-Hungerbuehler, A Katrin; Spiri, Andrea M; Riond, Barbara; Grest, Paula; Boretti, Felicitas S; Hofmann-Lehmann, Regina

2015-03-24

Therapeutic vaccinations have a potential application in infections where no curative treatment is available. In contrast to HIV, efficacious vaccines for a cat retrovirus, feline leukemia virus (FeLV), are commercially available. However, the infection is still prevalent, and no effective treatment of the infection is known. By vaccinating persistently FeLV-infected cats and presenting FeLV antigens to the immune system of the host, e.g., in the form of recombinant and/or adjuvanted antigens, we intended to shift the balance toward an advantage of the host so that persistent infection could be overcome by the infected cat. Two commercially available FeLV vaccines efficacious in protecting naïve cats from FeLV infection were tested in six experimentally and persistently FeLV-infected cats: first, a canarypox-vectored vaccine, and second, an adjuvanted, recombinant envelope vaccine was repeatedly administered with the aim to stimulate the immune system. No beneficial effects on p27 antigen and plasma viral RNA loads, anti-FeLV antibodies, or life expectancy of the cats were detected. The cats were unable to overcome or decrease viremia. Some cats developed antibodies to FeLV antigens although not protective. Thus, we cannot recommend vaccinating persistently FeLV-infected cats as a means of improving their FeLV status, quality of life or life expectancy. We suggest testing of all cats for FeLV infection prior to FeLV vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

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)

Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter pylori eradication.

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Jeong, Su Jin; Kim, Jie-Hyun; Jung, Da Hyun; Lee, Kyoung Hwa; Park, Soon Young; Song, Yungoo; Kang, Il-Mo; Song, Young Goo

2018-02-12

Novel antibacterial strategies against Helicobacter pylori are needed because H. pylori strains are acquiring resistance to antibiotics. We evaluated the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment regimens in a murine model of H. pylori infection. Two groups of 10 rats were administered either smectite or S-GEN to measure coverage of the gastric mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups of 10 mice each given different treatments, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces. The levels of proinflammatory cytokines were examined. S-GEN was retained in the gastric mucosal layer with a >60% distribution ratio for up to 1 h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared with that of untreated mice or mice treated with other regimens. The cure rates in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%, 60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the faeces of mice were 90% and 100% in Group III with standard therapy and Group V with triple therapy including S-GEN, respectively. S-GEN triple therapy also reduced the levels of proinflammatory cytokines. These results suggest that S-GEN is a promising and effective therapeutic agent for the treatment of H. pylori infection. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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)

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

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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

Academic Locus of Control, Tendencies Towards Academic Dishonesty and Test Anxiety Levels as the Predictors of Academic Self-Efficacy

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Yesilyurt, Etem

2014-01-01

Many studies have focused on finding the level of effect that academic locus of control, tendencies towards academic dishonesty, and test anxiety levels have had on academic self-efficacy, and providing a separate explanation ratio for each. The relationship among the effects of the academic locus of control, tendencies towards academic…

Financial Strain and Regional Unemployment as Barriers to Job Search Self-Efficacy: A Test of Social Cognitive Career Theory

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Dahling, Jason J.; Melloy, Robert; Thompson, Mindi N.

2013-01-01

Social cognitive career theory (SCCT) emphasizes the potential impact of contextual barriers on vocational self-efficacy, interests, and goals. However, most tests of SCCT to date have focused exclusively on person-level, perceptual barriers rather than objective, macroeconomic barriers that may influence large groups of people. In this study, we…

Graphene-based platforms for cancer therapeutics

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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

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

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

2017-09-01

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

Coaching in self-efficacy improves care responses, health and well-being in dementia carers: a pre/post-test/follow-up study.

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Chenoweth, Lynn; Stein-Parbury, Jane; White, Danielle; McNeill, Georgene; Jeon, Yun-Hee; Zaratan, Beverley

2016-05-04

Maintaining the health and well-being of family carers of people with dementia is vital, given their potential for experiencing burden associated with the role. The study aimed to help dementia carers develop self-efficacy, be less hassled by the caring role and improve their health and well-being with goal-directed behaviour, by participating in an eight module carer coaching program. The study used mixed methods in a pre/post-test/follow-up design over 24 months, with assignment of consented dementia carers to either individualised (n = 16) or group coaching (n = 32), or usual carer support services (n = 43), depending on preference. Care-giving self-efficacy and hassles, carer health, well-being and goal-directed behaviours were assessed over time. Analysis of Variance (ANOVA) was used to compare changes over time and the effects of coaching on carer self-efficacy, hassles and health, using the Univariate General Linear Model (GLM). All carers were hassled by many aspects of caring at baseline. Participants receiving coaching reported non-significant improvements in most areas of self-efficacy for caring, hassles associated with caring and self-reported health at post-test and follow-up, than did carers receiving usual carer support. Group coaching had greater success in helping carers to achieve their goals and to seek help from informal and formal support networks and services. The study outcomes were generally positive, but need to be interpreted cautiously, given some methodological limitations. It has been shown, however, that health staff can assist dementia carers to develop self-efficacy in better managing their family member's limitations and behaviour, seek help from others and attend to their health. Teaching carers to use goal-directed behaviour may help them achieve these outcomes.

Replacement of the in vivo neutralisation test for efficacy demonstration of tetanus vaccines ad us. vet.

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Rosskopf, Ute; Noeske, Kerstin; Werner, Esther

2005-01-01

The bacterium Clostridium (C.) tetani is an ubiquitous pathogen. This anaerobic, gram-positive bacterium can form spores and can be found in the whole environment. It enters the body via injuries of the skin and wounds where it releases the neurotoxin "tetanospasmin" (= tetanus toxin). The animals most susceptible to tetanus infection are horses and sheep. Only active immunisation by tetanus vaccine provides effective protection against tetanus intoxication. The marketing authorisation requirements stipulate that efficacy of tetanus vaccines ad us. vet. must be demonstrated in all target animal species via determination of neutralising tetanus serum antitoxin concentrations. The standard method used for this purpose is still the toxin neutralisation test (TNT), as it quantifies the tetanus toxin-neutralising effect of tetanus serum antibodies in vivo. In this test, tetanus toxin is added to dilutions of serum from vaccinated horse and sheep. The serum dilutions are then administered to mice or guinea pigs, which are observed for toxic symptoms. Against the background of animal protection, the goal of one project of the Paul-Ehrlich-Institut (Bundesministerium fuer Bildung und Forschung (Federal Ministry for Education and Research), 0312636) was to establish an alternative to the toxin neutralisation test, enabling the testing of efficacy of tetanus vaccines with serological in vitro methods. For this purpose, a so-called double antigen ELISA (DAE) was established which enables the testing of sera of different species in one assay. In addition, the sera were tested in an indirect ELISA for horses and sheep separately. Altogether, ten groups of horses and eight groups of sheep were immunised with ten animals per group each. The tetanus vaccines comprised almost all products authorised for the German market at the start of the project. 564 horse sera and 257 sheep sera were tested using the two ELISA methods. Some sera were also tested in vivo. The kinetics of

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

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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.

The testing of sanitizers efficacy to enterococci adhered on glass surfaces

Directory of Open Access Journals (Sweden)

Margita Čanigová

2015-08-01

Full Text Available The aim of this work was to test the ability of 6 strains of enterococci to adhere on glass surfaces in environment with different content of milk residues and then to evaluate efficacy of 2 commercial sanitizers (alkaline and acidic used in milk production. Tested enterococci were isolated from milk, dairy products and from rinse water after sanitation milking machine. Suspension of enterococci (8 log CFU.ml-1 was prepared in phosphate buffered saline (PBS, PBS with content 0.1% and 1% of skimmed reconstituted milk. Glass plates were immersed into bacterial suspension for 1 h at 37 °C. The number of enterococci adhered on glass surface in PBS achieved an average value 3.47 log CFU.mm-2, in PBS with 0.1% of milk 2.90 CFU.mm-2, in PBS with 1% of milk 2.63 CFU.mm-2. Differences between the tested files were not statistically significant (p >0.05. In the second part of work the glass plates with adhered enterococci were exposed to the effect of alkaline sanitizer (on basis of NaOH and NaClO, respectively acidic sanitizer (on basis of H3PO4. Sanitation solutions were prepared and tested according to manufacturer recommendations (concentration 0.25%, contact time 20 min, temperature   20 °C. Alkaline sanitation solution was 100% effective against all tested enterococci regardless to content of milk residues in environment. Acidic sanitation solution was 100% effective only against E. faecalisD (isolated from rinse water after sanitation. Average value of reduction of enterococci with acidic sanitation solution, which were on glass plates in environment PBS was 2.84 CFU.mm-2, in PBS with 0.1% of milk was 2.45 CFU.mm-2 and in PBS with 1% of milk was 2.16 CFU.mm-2. It can be concluded, that increase of milk residues in environment decrease the adhesion of enterococci on glass surface, but also effectiveness of acidic sanitation solution.

[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.

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

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

2014-01-01

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

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...

Therapeutic effect of beta radiation on onychomycosis: An innovative treatment

International Nuclear Information System (INIS)

Afroz, S.; Islam, N.; Rashid, H.; Shahidullah, M.; Ali, S.; Islam, S.K.M.; Hossain, S.; Ali, N.

2005-01-01

Full text: Onychomycosis is the most frequent cause of nail disease and the most prevalent type of dermatophytosis in Bangladesh. The humid and warm climate of this tropical country is congenial for the growth of fungi. Therapeutic limitations of conventional antimycotic agents in respect of low cure rates, high relapse rate, inherent side effects, long duration of treatment and high cost in treating onychomycosis have provided clear incentives to explore alternative forms of treatment procedure. The objectives of the present thesis work were: (i) To use beta radiation as a curative therapy for Onychomycosis, optimisation of its dosages and to promote an innovative clinical development in the field of therapeutic application of nuclear medicine; (ii) To assess the efficacy of beta radiation either alone or in combination with conventional antifungal therapy; and (iii) To reduce the duration of drug exposure and cost of treatment for onychomycosis. This is a PhD research work under the University of Dhaka and was sponsored by the Ministry of Science and Information and Communication Technology, Government of the people's republic of Bangladesh. This study is an open, randomised and controlled trial to verify the efficacy of beta radiation in patients with onychomycosis. Using the appropriate statistical formula, sample size of the study population was determined and in each group 92 patients were assigned. With an assumption of patients drop out and for better statistical analysis, a total of 330 patients, who fulfilled the inclusion criterion having diagnosed to have onychomycosis clinically and mycological were randomly allocated to enter in therapeutic regimen. Study population was randomised in three groups. Group A (n =110) received griseofulvin orally 500 mg once daily for 12-16 weeks; Group B (n=110) received beta radiation, 500 rads bi-weekly for 3 weeks (total 2500 rads); and Group C (n=110) received combined beta radiation (total 2500 rads in 3 weeks) and

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.

Efficacy of a variety of disinfectants against Listeria spp.

OpenAIRE

Best, M; Kennedy, M E; Coates, F

1990-01-01

The efficacy of 14 disinfectants against Listeria innocua and two strains of Listeria monocytogenes in the presence of organic matter was studied. Quantitative efficacy tests were used. Many of the disinfectants tested were not as effective on Listeria spp. when the test organisms were dried onto the surface of steel disks (carrier tests) as they were when the organisms were placed in suspension (suspension test). The presence of whole serum and milk (2% fat) further reduced the disinfectant ...

Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial.

Science.gov (United States)

Choudhary, Sv; Bisati, S; Singh, Al; Koley, S

2013-11-01

To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris. This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams. In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each. Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud's dextrose agar with chloramphenicol and cycloheximide. Statistical analysis was done using students paired and unpaired t-tests from the data obtained. Comparison between Group A and Group B for complete cure (clinical and mycological) showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1(st) and 2(nd) week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2(nd) week

Efficacy and safety of terbinafine hydrochloride 1% cream vs. sertaconazole nitrate 2% cream in tinea corporis and tinea cruris: A comparative therapeutic trial

Directory of Open Access Journals (Sweden)

S V Choudhary

2013-01-01

Full Text Available Context: To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris. Aims: This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams. Settings and Design: In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream and Group B (treatment with sertaconazole cream. A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each. Materials and Methods: Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud′s dextrose agar with chloramphenicol and cycloheximide. Statistical Analysis Used: Statistical analysis was done using students paired and unpaired t-tests from the data obtained. Results: Comparison between Group A and Group B for complete cure (clinical and mycological showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1 st and 2 nd week, statistically non

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

Directory of Open Access Journals (Sweden)

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.

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.)

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)

The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

Directory of Open Access Journals (Sweden)

Richard J. Davis

2017-07-01

Full Text Available Age-related macular degeneration (AMD is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC-derived RPE cells (RPESC-RPE preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.

Does Digital Game Interactivity Always Promote Self-Efficacy?

Science.gov (United States)

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.

Relationships among communication competence, self-efficacy, and job satisfaction in Korean nurses working in the emergency medical center setting.

Science.gov (United States)

Park, Min Sook; Jeoung, Yeonok; Lee, Hye Kyung; Sok, Sohyune R

2015-06-01

The communication competence of nurses working in emergency medical center settings is essential to establish a therapeutic nurse-patient relationship. Education and strategic development are required to improve the communication competence of emergency room (ER) nurses. This study was conducted to determine the relationships among individual communication competence, self-efficacy, and job satisfaction in Korean nurses in the emergency medical center setting. A cross-sectional descriptive design was adopted. The study sample included 214 nurses at 11 emergency medical centers in Seoul and Kyunggi-Do, Korea. Measures used included the Global Interpersonal Communication Competence, self-efficacy scale, and job satisfaction scale. The collected data were analyzed using the SPSS version 18.0 statistical software program and included descriptive statistics (frequency, percentage, mean, standard deviation, independent t test, analysis of variance, and Pearson's correlation coefficient). The degrees of communication competence and self-efficacy of ER nurses were good, with higher scores than the median values. However, the degree of job satisfaction was poor, indicating a lower score than the median value. Religious affiliation and previous participation in communication education each had a significant impact on communication competence. Religious affiliation and time of worse duty each had a significant impact on self-efficacy. Length of career (year) in the emergency medical center and type of hospital each had a significant impact on job satisfaction. Positive correlations were identified among communication competence, self-efficacy, and job satisfaction. This study supported the presence of significant correlations among communication competence, self-efficacy, and job satisfaction. Thus, it is necessary to develop training programs that are customized to individual characteristics such as self-efficacy and job satisfaction to improve the communicative competence

Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.

Science.gov (United States)

Weber, Helga; Valbuena, José R; Barbhuiya, Mustafa A; Stein, Stefan; Kunkel, Hana; García, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime A; Kurtz, Stephen E; Tyner, Jeffrey W; Calderon, Juan Francisco; Corvalán, Alejandro H; Grez, Manuel; Pandey, Akhilesh; Leal-Rojas, Pamela; Roa, Juan C

2017-04-18

Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.

Animal models for microbicide safety and efficacy testing.

Science.gov (United States)

Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

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.

Science.gov (United States)

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.

Toxicological perspectives of inhaled therapeutics and nanoparticles.

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Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

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.

Directory of Open Access Journals (Sweden)

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.