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Sample records for therapeutic efficacy test

  1. Identification of fragile X syndrome specific molecular markers in human fibroblasts: a useful model to test the efficacy of therapeutic drugs.

    Science.gov (United States)

    Kumari, Daman; Bhattacharya, Aditi; Nadel, Jeffrey; Moulton, Kristen; Zeak, Nicole M; Glicksman, Anne; Dobkin, Carl; Brick, David J; Schwartz, Philip H; Smith, Carolyn B; Klann, Eric; Usdin, Karen

    2014-12-01

    Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and autism. It is caused by the absence of the fragile X mental retardation 1 (FMR1) gene product, fragile X mental retardation protein (FMRP), an RNA-binding protein involved in the regulation of translation of a subset of brain mRNAs. In Fmr1 knockout mice, the absence of FMRP results in elevated protein synthesis in the brain as well as increased signaling of many translational regulators. Whether protein synthesis is also dysregulated in FXS patients is not firmly established. Here, we demonstrate that fibroblasts from FXS patients have significantly elevated rates of basal protein synthesis along with increased levels of phosphorylated mechanistic target of rapamycin (p-mTOR), phosphorylated extracellular signal regulated kinase 1/2, and phosphorylated p70 ribosomal S6 kinase 1 (p-S6K1). The treatment with small molecules that inhibit S6K1 and a known FMRP target, phosphoinositide 3-kinase (PI3K) catalytic subunit p110β, lowered the rates of protein synthesis in both control and patient fibroblasts. Our data thus demonstrate that fibroblasts from FXS patients may be a useful in vitro model to test the efficacy and toxicity of potential therapeutics prior to clinical trials, as well as for drug screening and designing personalized treatment approaches. © 2014 WILEY PERIODICALS, INC.

  2. Therapeutic efficacy of facet joint blocks.

    Science.gov (United States)

    Gorbach, Christoph; Schmid, Marius R; Elfering, Achim; Hodler, Juerg; Boos, Norbert

    2006-05-01

    The objective of our study was to investigate outcome predictors of short- and medium-term therapeutic efficacy of facet joint blocks. Forty-two patients with chronic lower back pain who were undergoing facet joint blocks at one (n = 29) or two (n = 13) levels were analyzed. All patients underwent MRI or CT of the lumbar spine within 5 months before the facet joint blocks. The facet joint blocks were performed under fluoroscopic guidance. A small amount ( 1 week) and medium-term effect (> 3 months), were collected by a structured telephone interview. CT and MRI were reviewed with regard to the extent of facet joint abnormalities. Multiple logistic regression analyses were conducted to identify outcome predictor for efficacy of facet joint blocks. A positive immediate effect was seen in 31 patients (74%). A positive medium-term effect was found in 14 patients (33%). Pain alleviated by motion (p = 0.035) and the absence of joint-blocking sensation (p = 0.042) predicted pain relief. However, the extent of facet joint osteoarthritis on MRI and CT was not a significant predictor for outcome (p = 0.57-0.95). Facet joint blocks appear to have a beneficial medium-term effect in one third of patients with chronic lower back pain and may therefore be a reasonable adjunct to nonoperative treatment. However, outcome appears to depend on clinical, not on morphologic, imaging findings.

  3. Chemoprophylactic and therapeutic efficacy of thymol in murine cystic echinococcosis.

    Science.gov (United States)

    Maggiore, M; Pensel, P E; Denegri, G; Elissondo, M C

    2015-10-01

    Cystic echinococcosis is a zoonotic disease caused by the larval stage of the cestode Echinococcus granulosus. The drugs commonly used against cystic echinococcosis are benzimidazoles. Unfortunately, 20%-40% of cases do not respond favorably to such chemotherapy. Consequently, the search of new therapeutic alternatives such as the use of traditional medicinal plants has been increased. The aim of the current experimental work was to investigate the chemoprophylactic and clinical efficacy of thymol on mice infected with E. granulosus metacestodes. Thymol (40 mg/kg) was administered under two different therapeutic schemes: dosing every 24h over 20 days and treatment every 12h for 10 days. Thymol demonstrated efficacy against experimental murine cystic echinococcosis. The chemoprophylactic and therapeutic effects of thymol were comparable to that of albendazole. Due to the lack of toxicity observed in mice at the tested doses; we consider that thymol is a potential alternative to be applied for the treatment of human hydatid disease. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    Background: Therapeutic Ultrasound (TUS) is considered as one of the physiotherapeutic modalities used in the management of osteoarthritis. However, its effectiveness is still controversial, ill understood and ambiguous. Purpose: The main purpose of the present study was to determine the therapeutic efficacy of ...

  5. Therapeutic efficacy of sulfadoxine-pyrimethamine for Plasmodium ...

    African Journals Online (AJOL)

    Objectives. To assess the therapeutic efficacy of sulfadoxinepyrimethamine (SP) after 5 years of use as first-line treatment of uncomplicated Plasmodium falciparum malaria, and thus guide the selection of artemisinin-based combination therapy in Mpumalanga, South Africa. Design. An open-label, in vivo therapeutic ...

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

    African Journals Online (AJOL)

    Erah

    Purpose: To develop a highly accurate molecular assay for evaluating the efficacy of metronidazole and some antifungal agents with meglumine antimoniate against L. infantum visceral leishmaniasis in different mouse tissues. Methods: The assay was performed with the Light-Cycler system using SYBR Green I and ...

  7. Monitoring therapeutic efficacy in breast carcinomas.

    Science.gov (United States)

    Tardivon, Anne A; Ollivier, Liliane; El Khoury, Carl; Thibault, Fabienne

    2006-11-01

    The aim of imaging during and after neoadjuvant therapy is to document and quantify tumor response: has the tumor size been accurately measured? Certainly, the most exciting information for the oncologists is: can we identify good or nonresponders, and can we predict the pathological response early after the initiation of treatment? This review article will discuss the role and the performance of the different imaging modalities (mammography, ultrasound, magnetic resonance imaging and FDG-PET imaging) for evaluating this therapeutic response. It is important to emphasize that, at this time, clinical examination and conventional imaging (mammography and ultrasound) are the only methods recognized by the international criteria. Magnetic resonance imaging and FDG-PET imaging are very promising for predicting the response early after the initiation of neoadjuvant chemotherapy.

  8. Monitoring therapeutic efficacy in breast carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Tardivon, Anne A.; Ollivier, Liliane; Khoury, Carl El; Thibault, Fabienne [Institut Curie, Department of Radiology, Paris (France)

    2006-11-15

    The aim of imaging during and after neoadjuvant therapy is to document and quantify tumor response: has the tumor size been accurately measured? Certainly, the most exciting information for the oncologists is: can we identify good or nonresponders, and can we predict the pathological response early after the initiation of treatment? This review article will discuss the role and the performance of the different imaging modalities (mammography, ultrasound, magnetic resonance imaging and FDG-PET imaging) for evaluating this therapeutic response. It is important to emphasize that, at this time, clinical examination and conventional imaging (mammography and ultrasound) are the only methods recognized by the international criteria. Magnetic resonance imaging and FDG-PET imaging are very promising for predicting the response early after the initiation of neoadjuvant chemotherapy. (orig.)

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

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

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

  10. Therapeutic Efficacy Of Cotecxin (R) alone and Its Combination with ...

    African Journals Online (AJOL)

    The therapeutic efficacy of Cotecxin(R) (Dihydroartemisinin) alone and its combination with diminazene aceturate (Berenil(R)) was studied in rats infected with Federe strain of Trypanosoma brucei brucei. Fifty healthy adult albino rats of both sexes weighing between 100-180g used were divided into five groups (A-E) of 10 ...

  11. Therapeutic Efficacy of Exercise and Laser Therapy in the ...

    African Journals Online (AJOL)

    Therapeutic Efficacy of Exercise and Laser Therapy in the Symptomatic Management of Osteoarthritis of the knee joint. ... Both groups received standard care of exercise (mode: low intensity, time: 15 minutes) per session for 6 weeks. In addition to the exercise, the LLLT group received 18 LLLT (Laser class 3b, frequency of ...

  12. Therapeutic Efficacy of Intermittent Cryotherapy in the Management ...

    African Journals Online (AJOL)

    Therapeutic Efficacy of Intermittent Cryotherapy in the Management of Closed Soft Tissue Injuries. ... The study has demonstrated that intermittent mode of cryotherapy application for a period of 20 mins. on alternate days could produce optimal pain relief among subjects who sustained various CSTIs. The procedure was ...

  13. Therapeutic efficacy of artemether-lumefantrine for treatment of ...

    African Journals Online (AJOL)

    Purpose: To review current therapeutic efficacy of artemether-lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in patients in Enugu State, Nigeria. Methods: One hundred and fifty four malaria patients from three different Local Government Areas (LGA) of Enugu State, southeastern Nigeria ...

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

    Science.gov (United States)

    Thram, Diane

    2015-01-01

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

  15. Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated ...

    African Journals Online (AJOL)

    Objectives. To assess therapeutic efficacy of sulfadoxineyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa. Se'tting. Tonga district with a population of 116 418 and subject to seasonal malaria, with an average annual incidence ; 3 200 ...

  16. Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease.

    Science.gov (United States)

    Fabbro, Diana; Velazquez, Elsa; Bizai, Maria Laura; Denner, Susana; Olivera, Verónica; Arias, Enrique; Pravia, Carlos; Ruiz, Andrés M

    2013-01-01

    This work compared the time at which negative seroconversion was detected by conventional serology (CS) and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.

  17. Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease

    Directory of Open Access Journals (Sweden)

    Diana Fabbro

    2013-06-01

    Full Text Available This work compared the time at which negative seroconversion was detected by conventional serology (CS and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.

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

    Directory of Open Access Journals (Sweden)

    Ana-Maria BOTEZAN

    2015-12-01

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

  19. Therapeutic efficacy of artesunate - amiodaquine for treating uncomplicated falciparum malaria at Ghindae Zonal Referral Hospital, Eritrea.

    Science.gov (United States)

    Mohammed, Abdu O; Tewolde, Seltene; Estifanos, Dawit; Tekeste, Yohannes; Osman, Mohammed-Hamid

    2018-01-01

    The aim of this study was to assess the efficacy of artesunate-amodiaquine (AS+AQ) which is the first-line treatment for uncomplicated falciparum malaria in Eritrea. The study was conducted from December 2014 to March 2015 in Ghindae Zonal Referral Hospital in Northern Red Sea Zone. Out of 481 patients screened, 103 were enrolled in the study. The therapeutic efficacy test was done as per the WHO protocol for a period of 28days of follow-up. The PCR-uncorrected treatment outcome was classified as adequate clinical and parasitological response (ACPR) in 95 patients, which meant the cure rate was 96.0 (95% CI: 89.7%-98.5%) after survival analysis. Therapeutic efficacy of AS+AQ still meets the WHO efficacy criteria for its continued use in the study area as the first-line drug against uncomplicated falciparum malaria. However, further studies are needed using correction with molecular markers to monitor therapeutic efficacy of antimalarial drugs in this area. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2005-10-31

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

  1. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

    Directory of Open Access Journals (Sweden)

    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.

  2. Psychometric properties of the Chinese version of the Perceived Therapeutic Efficacy Scale for type 2 diabetes.

    Science.gov (United States)

    Wu, Shu-Fang Vivienne; Courtney, Mary; Edwards, Helen; McDowell, Jan; Shortridge-Baggett, Lillie M; Chang, Pei-Jen

    2008-03-01

    The purpose of this study was to test the psychometric properties of the Perceived Therapeutic Efficacy Scale (PTES) for type 2 diabetes with a Taiwanese sample. The mortality rate and health care cost of diabetes have dramatically increased in Taiwan, with many people with diabetes lacking the ability to control their disease appropriately. Addressing this problem requires enhancing self-efficacy towards self-management. Thus, there is a particular need for research into developing a diabetes-specific self-efficacy measurement instrument in Taiwan. This study was undertaken in two stages. Stage 1 consisted of forward and back translation of the PTES into Chinese and examination of content validity. Stage 2 established the validity and reliability of the Chinese version of PTES (C-PTES). A total of 230 people with type 2 diabetes aged 30 years or more from a diabetes outpatient clinic and taking oral medicine were recruited for psychometric testing. Significant criterion-related validity was demonstrated between the C-PTES and the Summary of Diabetes Self-Care Activities scores (r=0.32; pPTES converged well with the General Self-Efficacy Scale in measuring self-efficacy (r=0.42; pPTES. The C-PTES requires future studies to confirm the psychometric properties.

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

    Science.gov (United States)

    Hauser, Mike; Hays, Danica G.

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Roizman, Dan; Vidaillac, Celine; Givskov, Michael

    2017-01-01

    engineered strain PAO1/pBAD-yhjH resulted in increased antimicrobial efficacy and synergy of the imipenem-tobramycin combination. These results support the use of biofilm dispersal to enhance antimicrobial efficacy in the treatment of biofilm-associated infections, representing a promising therapeutic...

  6. Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness

    Science.gov (United States)

    Walker, Martin; Specht, Sabine; Churcher, Thomas S.; Hoerauf, Achim; Taylor, Mark J.; Basáñez, María-Gloria

    2015-01-01

    Background. Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment. Methods. A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes. Results. The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%–94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%–80%, from approximately 10 years to 2–3 years. Conclusions. The efficacy parameters are pertinent to the prospects of using doxycycline on a “test and treat” basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings. PMID:25537873

  7. Therapeutic efficacy and macrofilaricidal activity of doxycycline for the treatment of river blindness.

    Science.gov (United States)

    Walker, Martin; Specht, Sabine; Churcher, Thomas S; Hoerauf, Achim; Taylor, Mark J; Basáñez, María-Gloria

    2015-04-15

    Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment. A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes. The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%-94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%-80%, from approximately 10 years to 2-3 years. The efficacy parameters are pertinent to the prospects of using doxycycline on a "test and treat" basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  8. Relative Therapeutic Efficacy of the Treadmill and Step Bench in ...

    African Journals Online (AJOL)

    umar

    Summary. The aim of this research is to compare the efficacy of treadmill and step bench exercises in hemiparetic gait rehabilitation. Previous studies have supported the use of treadmill and step bench exercises in gait rehabilitation. Nineteen patients were recruited for an 8-week, 2-group quasi-experimental study which ...

  9. Relative Therapeutic Efficacy of the Treadmill and Step Bench in ...

    African Journals Online (AJOL)

    The aim of this research is to compare the efficacy of treadmill and step bench exercises in hemiparetic gait rehabilitation. Previous studies have supported the use of treadmill and step bench exercises in gait rehabilitation. Nineteen patients were recruited for an 8-week, 2-group quasi-experimental study which was ...

  10. Assessment of the Therapeutic Efficacy of Two Artemisinin-Based ...

    African Journals Online (AJOL)

    Plasmodium falciparum has developed resistance to almost every class of antimalarial compounds. As a result of this, the World Health Organization has recommended artemisinin-based combination therapy as first line treatment for P. falciparum malaria. There is however need for the continuous monitoring of the efficacy ...

  11. Relative Therapeutic Efficacy of Phonophoresis and Cryotherapy as ...

    African Journals Online (AJOL)

    This study was designed to investigate the efficacy of phonophoresis and cryotherapy as combined therapy (double-modality therapy – DMT) in the management of pain among subjects with musculoskeletal injuries (MSIs). Subjects were assigned randomly to one of three groups: DMT group (n=17) received cryotherapy ...

  12. Therapeutic Efficacy of Methyl Salicylate Phonophoresis in the ...

    African Journals Online (AJOL)

    Result: The difference in the severity of pain before and after treatment was statistically significant(P < 0.05). 13(93%) subjects were pain free and fit for discharge after about two-half weeks of treatment. Conclusion: The study has demonstrated the efficacy of methyl salicylate phonophoresis in the management of ...

  13. Therapeutic efficacy of nanomedicines for prostate cancer: An update.

    Science.gov (United States)

    Lakshmanan, Vinoth-Kumar

    2016-01-01

    Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and time-dependent manner. Nanomedicines have been developed for therapeutic application in combination with image-guided therapy in real time. The scope of one of these nanomedicines, Abraxane (paclitaxel), may be extended to prostate cancer therapeutic applications for better quality of patient life and longer survival. This review provides an update on the latest directions and developments in nanomedicines for prostate cancer.

  14. Therapeutic efficacy of nanomedicines for prostate cancer: An update

    Directory of Open Access Journals (Sweden)

    Vinoth-Kumar Lakshmanan

    2016-01-01

    Full Text Available Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and timedependent manner. Nanomedicines have been developed for therapeutic application in combination with image-guided therapy in real time. The scope of one of these nanomedicines, Abraxane (paclitaxel, may be extended to prostate cancer therapeutic applications for better quality of patient life and longer survival. This review provides an update on the latest directions and developments in nanomedicines for prostate cancer.

  15. 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.

  16. Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.

    Science.gov (United States)

    Roymans, Dirk; Alnajjar, Sarhad S; Battles, Michael B; Sitthicharoenchai, Panchan; Furmanova-Hollenstein, Polina; Rigaux, Peter; Berg, Joke Van den; Kwanten, Leen; Ginderen, Marcia Van; Verheyen, Nick; Vranckx, Luc; Jaensch, Steffen; Arnoult, Eric; Voorzaat, Richard; Gallup, Jack M; Larios-Mora, Alejandro; Crabbe, Marjolein; Huntjens, Dymphy; Raboisson, Pierre; Langedijk, Johannes P; Ackermann, Mark R; McLellan, Jason S; Vendeville, Sandrine; Koul, Anil

    2017-08-01

    Respiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure-activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs with JNJ-53718678, or with an equally active close analog, efficiently inhibits established acute lower respiratory tract infection in the animals, even when treatment is delayed until external signs of respiratory syncytial virus illness have become visible. Together, these data suggest that JNJ-53718678 is a promising candidate for further development as a potential therapeutic in patients at risk to develop respiratory syncytial virus acute lower respiratory tract infection.Respiratory syncytial virus causes lung infections in children, immunocompromised adults, and in the elderly. Here the authors show that a chemical inhibitor to a viral fusion protein is effective in reducing viral titre and ameliorating infection in rodents and neonatal lambs.

  17. 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.

  18. Testing of Compounds for Efficacy against Schistosomiasis.

    Science.gov (United States)

    1987-08-25

    2 UNCLASSIFIED DAMDi7-95-C-5209 F/ G 6/15 UL 11𔃿 j j . 11_. W-I - - % (*J~f ~ HP OlIC FILE COPY *AD "Testing of Compounds for Efficacy Against...Liang, Y.S., 1974. Cultivation of Bulinus (5hy Q pis) g2.kous (Morelet) and BiQmphalaria pfeiffri pfeifferi (Krauss), snail hosts of schistosomiasis...Digenea). flacQ1. g " 11:225:280. 10. Sandt, D.G., Bruce, H.I. and Radke, M.G., 1965. A system for mass producing the snail Ausatra1Qbjiz Lbi.atus and

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

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    Ildiko Barabasi

    2016-11-01

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

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

    Science.gov (United States)

    Williams, S. Lloyd; And Others

    1989-01-01

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

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

    Science.gov (United States)

    Opoku-Acheampong, Alexander B; Unis, Dave; Henningson, Jamie N; Beck, Amanda P; Lindshield, Brian L

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Alexander B Opoku-Acheampong

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

  3. The efficacy of therapeutic ultrasound for rotator cuff tendinopathy: A systematic review and meta-analysis.

    Science.gov (United States)

    Desmeules, François; Boudreault, Jennifer; Roy, Jean-Sébastien; Dionne, Clermont; Frémont, Pierre; MacDermid, Joy C

    2015-08-01

    A systematic review and meta-analysis on the efficacy of therapeutic ultrasound (US) in adults suffering from rotator cuff tendinopathy. A literature search was conducted in four databases for randomized controlled trials (RCT) published until 12/2013, comparing the efficacy of US to any other interventions in adults suffering from rotator cuff tendinopathy. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of included studies. Data were summarized qualitatively or quantitatively. Eleven RCTs with a low mean methodological score (50.0% ± 15.6%) were included. Therapeutic US did not provide greater benefits than a placebo intervention or advice in terms of pain reduction and functional improvement. When provided in conjunction with exercise, US therapy is not superior to exercise alone in terms of pain reduction and functional improvement (pooled mean difference of the Constant-Murley score: -0.26 with 95% confidence interval of -3.84 to 3.32). Laser therapy was found superior to therapeutic US in terms of pain reduction. Based on low to moderate level evidence, therapeutic US does not provide any benefit compared to a placebo or advice, to laser therapy or when combined to exercise. More methodologically sound studies on the efficacy of therapeutic US are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Therapeutic efficacy of the F8-IL2 immunocytokine in a metastatic mouse model of lung adenocarcinoma.

    Science.gov (United States)

    Wieckowski, Sébastien; Hemmerle, Teresa; Prince, Spasenja Savic; Schlienger, Béatrice Dolder; Hillinger, Sven; Neri, Dario; Zippelius, Alfred

    2015-04-01

    Antibody-cytokine fusion proteins (immunocytokines) represent a novel class of armed antibodies in oncology. In particular, IL2- and TNF-based immunocytokines targeting the EDB domain of fibronectin and the A1 domain of tenascin-C have demonstrated promising anti-tumor activity and are currently investigated in Phase I and Phase II clinical trials. To advance the development of immunocytokines for NSCLC, we here report on the therapeutic efficacy of F8-IL2, an immunocytokine directed against the alternatively spliced EDA domain of fibronectin in a fully immunocompetent, orthotopic model of NSCLC, and the characterization of the target antigen expression in human NSCLC specimens. We evaluated the therapeutic efficacy of the F8-IL2 immunocytokine utilizing a K-ras mutant, p53 deficient metastatic mouse model of NSCLC derived from the latest generation of genetically engineered and conditional tumor models. In parallel, we assessed the presence of the EDA domain of fibronectin by immunofluorescence in lung biopsies obtained from patients with NSCLC. The EDA domain of fibronectin was broadly expressed in lung metastases obtained from our model. Treatment with F8-IL2 induced substantial local changes within immune effector cell populations and demonstrated promising therapeutic efficacy as monotherapy. The target of F8-IL2, the EDA domain of fibronectin, was present in all human lung adenocarcinoma specimens tested. Both the therapeutic efficacy in a metastatic mouse model of NSCLC and the extensive presence of the EDA domain of fibronectin in human NSCLC biopsies support the rational development of therapies based on the F8-IL2 immunocytokine for the treatment of NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. De-qi, not psychological factors, determines the therapeutic efficacy of acupuncture treatment for primary dysmenorrhea.

    Science.gov (United States)

    Xiong, Jin; Liu, Fang; Zhang, Ming-Min; Wang, Wei; Huang, Guang-Ying

    2012-01-01

    To study the impact of De-qi (, obtaining qi) and psychological factors on the efficacy of acupuncture treatment for primary dysmenorrhea, with an attempt to explore the relationship among De-qi, psychological factors, and clinical efficacy. The patients with primary dysmenorrhea were randomly assigned to a group of acupuncture with manual manipulation (manipulation group, n=67) and an acupuncture group without manipulation (non-manipulation group, n=64). Pain intensity and pain duration were used as measures for evaluating the therapeutic efficacy of the acupuncture treatment. De-qi, the sensations a patient experienced during the acupuncture treatment, was scored on a 4-point scale by the subjects. In addition, the psychological factors, including belief in acupuncture, the level of nervousness, anxiety, and depression, were quantitatively assessed. The personality of the subject was assessed using the Eysenck personality questionnaire (EPQ) and 16 personality factor questionnaire (16PF). Complete data were obtained from 120 patients, 60 patients in each group. There were statistically significant differences in pain intensity (W=2410.0, P<0.01) and pain duration (W=3181.0, P<0.01) between the two groups. The number of De-qi acupoints (W=1150.5, P<0.01) and the average intensity of De-qi (W=1141.0, P<0.01) were significantly higher in the manipulation group as compared with their non-manipulation counterparts. The correlation coefficients between De-qi and therapeutic efficacy of acupuncture were greater than those between psychological factors and therapeutic efficacy. Compared with the psychological factors, De-qi contributed more to the pain-relieving effect of acupuncture in subjects with primary dysmenorrhea. Moreover, manual manipulation is a prerequisite for eliciting and enhancing the De-qi sensations, and De-qi is critical for achieving therapeutic effects.

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

    Science.gov (United States)

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

    2017-05-01

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

  7. Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy.

    Science.gov (United States)

    Mimura, Yusuke; Katoh, Toshihiko; Saldova, Radka; O'Flaherty, Roisin; Izumi, Tomonori; Mimura-Kimura, Yuka; Utsunomiya, Toshiaki; Mizukami, Yoichi; Yamamoto, Kenji; Matsumoto, Tsuneo; Rudd, Pauline M

    2017-06-08

    Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next-generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.

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

    Directory of Open Access Journals (Sweden)

    Miriam Canavese

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

  9. Therapeutic Efficacy of E-64-d, a Selective Calpain Inhibitor, in Experimental Acute Spinal Cord Injury

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    Zifeng Zhang

    2015-01-01

    Full Text Available This study aims to investigate the therapeutic effect of calpain inhibitor E-64-d on SCI and to find a new approach to treat SCI. When an SCI rat model was established, it was immediately administered with E-64-d. RT-PCR and Western blotting were used to determine the protein and mRNA levels of calpain 1 and 68-kD NFP. TUNEL staining and NeuN labeling were performed to analyze neuronal apoptosis in the lesion. Immunohistochemistry assay was carried out to observe the expressions of calpain 1 and GFAP. Cyclooxygenase-2 activity was measured to show the immune response status. Locomotor function was evaluated by inclined plane test and Basso, Beattie, and Bresnahan locomotor rating scale. The results showed that calpain 1 was activated after SCI occurred. Treatment with E-64-d decreased expressions of calpain 1 and GFAP, alleviated neuronal apoptosis, inhibited cyclooxygenase-2 activity, and resulted in the promoted locomotor function. Furthermore, combination of E-64-d and MP had better efficacy than did E-64-d or MP alone. E-64-d is expected to be applied to treat SCI, and its alliance with MP may provide a valid strategy for SCI therapy.

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

    Science.gov (United States)

    Zheng, Jin-Sheng

    2006-10-01

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

  11. Psychometric properties of the Perceived Therapeutic Efficacy Scale for adhering to a cholesterol-lowering diet.

    Science.gov (United States)

    Zheng, Yaguang; Terhorst, Lauren; Choo, Jina; Burke, Lora E

    2014-01-01

    Outcome expectancy may play an important role in behavior change. Previous studies tested the validity and the reliability of the Perceived Therapeutic Efficacy Scale (PTES), a scale that measures outcome expectancy related to adhering to a cholesterol-lowering diet. Further study was needed to examine its psychometric properties in a larger sample. The aim of this study was to test the psychometric properties of the 10-item PTES in a large sample. The PTES and the Connor Diet Habit Survey were administered to adults enrolled in a cardiac rehabilitation program. The final sample for the analysis (N = 224) was, on average, 69.35 years old and was predominantly men (66.50%) and white (92.40%); nearly all (96.00%) completed high school. The inter-item correlation matrix revealed that correlation coefficients were greater than 0.80 between 4 pairs of items, suggesting that the 4 items were redundant. After consulting with a content expert and an examination of item content, we removed the 4 redundant items (items 2, 3, 4, and 10) and reduced the scale to 6 items. Principal component analysis revealed a 1-factor scale with high loadings for the 6 items, each greater than 0.70. The reliability of the scale, measured by Cronbach's α, was 0.91. The total PTES score had a moderate correlation with self-reported behaviors of adhering to a cholesterol-lowering diet, as measured by the Connor Diet Habit Survey subscale for cholesterol and fat intake (r = 0.36, P PTES scale is reliable and valid to measure outcome expectancy related to adhering to a cholesterol-lowering diet.

  12. Nanoencapsulation of DMSA monoester for better therapeutic efficacy of the chelating agent against arsenic toxicity.

    Science.gov (United States)

    Yadav, Abhishek; Mathur, Rashi; Samim, Mohammed; Lomash, Vinay; Kushwaha, Pramod; Pathak, Uma; Babbar, Anil Kumar; Flora, Swaran Jeet Singh; Mishra, Anil Kumar; Kaushik, Mahabir Parshad

    2014-04-01

    Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for arsenic poisoning. Polymeric nanoparticles entrapping the DMSA monoester, which can evade the reticulo-endothelial system and have a long circulation time in the blood, were prepared. Particle characterization was carried out by transmission electron microscopy and dynamic light scattering. An in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA-encapsulated polymeric nanoparticles (nano- MiADMSA; 50 mg/kg orally for 5 days) and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood, brain, kidney and liver oxidative stress variables. The study also evaluated the histopathological changes in tissues and the chelating potential of the nanoformulation. Our results show that nano-MiADMSA have a narrow size distribution in the 50-nm range. We observed an enhanced chelating potential of nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical changes indicative of oxidative stress and efficient removal of arsenic from the blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove better therapeutic efficacy of the novel formulation for arsenic toxicity. The results from our study show better therapeutic efficacy of nano-MiADMSA in removing arsenic burden from the brain and liver.

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

    Directory of Open Access Journals (Sweden)

    Sheng-Mou Hsiao

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Guang-Huan Sun

    2010-10-01

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

  16. A randomized controlled trial on therapeutic efficacy and safety of No. 1 Decoction for common cold

    Directory of Open Access Journals (Sweden)

    Xiao-rong HUO

    2012-12-01

    Full Text Available Objective  To assess therapeutic efficacy and safety of No. 1 Decoction for common cold in patients. Methods  A randomized controlled trial was conducted to study 225 male military officers and soldiers who were suffering from common cold, while 6 of them who showed positive results in the colloidal gold immunochromatography assay (GICA for detecting Flu A/ B or LP were excluded. The remaining 219 patients were randomly allocated either to receive No. 1 Decoction (study group, n=111 or Ganmao Qingre Keli (control group, n=108 for 3 days. Grading quantization form for symptoms of common cold were filled for all patients. Clinical response rate, significant response rate and complete cure rate were analyzed. Adverse events were also observed and recorded. Results  In this trial, 2 patients in test group and 1 in study group were lost in follow-up, 13 cases with incomplete data were excluded (5 in study group, 8 in control group. 219 patients were included in FAS set and SS set, and data of 203 cases were observed in the PP set. In FAS set, the study group had a higher clinical recovery rate and effective rate than the control group (14.41% vs12.96%, P=0.755; 72.97% vs64.81%, P=0.192, and had a lower significant effective rate than control group (36.94% vs43.52%, P=0.321. The 95% confidence interval for the difference between the effective rates of study group and control group was (–4.06%-20.38%, Δ=–10%, suggesting No.1 Decoction might be as effective as Ganmao Qingre Keli. The results of PP set were similar to that of FAS set. Conclusion  No. 1 Decoction is a safe and effective drug for common cold.

  17. Efficacy and safety of the doxazosin gastrointestinal therapeutic system for the treatment of benign prostate hyperplasia.

    Science.gov (United States)

    Sun, Guang-Huan; Tsui, Ke-Hung; Wu, Tony T; Chang, Chao-Hsiang; Cheng, Chen-Li; Schou, Manjula

    2010-10-01

    This study was carried out to obtain information on the efficacy and safety of the controlled release formulation of the doxazosin Gastrointestinal Therapeutic System (GITS) in Taiwanese subjects with benign prostatic hyperplasia (BPH). Studies of doxazosin in Asian populations for this indication have lacked data particularly from Taiwan. This was an 8-week, post-marketing, open-label, non-comparative study. Eighty male subjects (mean age=64 years) with BPH received doxazosin GITS 4 mg once daily. At week 4, subjects who achieved an increase in maximum urinary flow rate (Qmax) of ≥3mL/s and a ≥30% reduction in the total International Prostate Symptom Score (IPSS) continued on doxazosin GITS 4 mg for the remaining 4 weeks; all other subjects were up-titrated to 8 mg once daily. Change from baseline at weeks 4 and 8 (primary endpoint) in IPSS and Qmax was evaluated using two-sided paired t tests for the intent-to-treat population. Safety was assessed throughout the study. A total of 53 (66.3%) subjects completed the study. Baseline Qmax and IPSS were 10.7+3.4 mL/s and 20.6+5.4, respectively. At week 8, a significant increase from baseline in Qmax of 3.3+4.6 mL/s (95% confidence interval = 2.2-4.4, pinformation for clinicians on the use of doxazosin GITS for the treatment of BPH, particularly in Taiwanese patients. Copyright © 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

  18. Neural Mobilization: A Systematic Review of Randomized Controlled Trials with an Analysis of Therapeutic Efficacy

    Science.gov (United States)

    Ellis, Richard F.; Hing, Wayne A.

    2008-01-01

    Neural mobilization is a treatment modality used in relation to pathologies of the nervous system. It has been suggested that neural mobilization is an effective treatment modality, although support of this suggestion is primarily anecdotal. The purpose of this paper was to provide a systematic review of the literature pertaining to the therapeutic efficacy of neural mobilization. A search to identify randomized controlled trials investigating neural mobilization was conducted using the key words neural mobilisation/mobilization, nerve mobilisation/mobilization, neural manipulative physical therapy, physical therapy, neural/nerve glide, nerve glide exercises, nerve/neural treatment, nerve/neural stretching, neurodynamics, and nerve/neural physiotherapy. The titles and abstracts of the papers identified were reviewed to select papers specifically detailing neural mobilization as a treatment modality. The PEDro scale, a systematic tool used to critique RCTs and grade methodological quality, was used to assess these trials. Methodological assessment allowed an analysis of research investigating therapeutic efficacy of neural mobilization. Ten randomized clinical trials (discussed in 11 retrieved articles) were identified that discussed the therapeutic effect of neural mobilization. This review highlights the lack in quantity and quality of the available research. Qualitative analysis of these studies revealed that there is only limited evidence to support the use of neural mobilization. Future research needs to re-examine the application of neural mobilization with use of more homogeneous study designs and pathologies; in addition, it should standardize the neural mobilization interventions used in the study. PMID:19119380

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    National Research Council Canada - National Science Library

    Li, Ying; Yuan, Jiani; Yang, Qian; Cao, Wei; Zhou, Xuanxuan; Xie, Yanhua; Tu, Honghai; Zhang, Ya; Wang, Siwang

    2014-01-01

    .... The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL...

  1. Individual prognosis regarding effectiveness of a therapeutic intervention using pre-therapeutic "kinesiology muscle test".

    Science.gov (United States)

    Waxenegger, Ingrid; Endler, P Christian; Wulkersdorfer, Beatrix; Spranger, Heinz

    2007-10-22

    Since a therapy's full positive effect and possible adverse effects are individual and not predictable for every single patient, scientists have been searching for methods to predict optimal effects of a therapy. This pilot study investigated the applicability of the "kinesiology muscle test" as a prognostic tool regarding effectiveness in a defined therapeutic procedure. Each of 11 test persons with elevated total cholesterol values received a naturopathic drug supposed to lower cholesterol level on a daily basis for eight consecutive weeks. Prior to treatment the "kinesiology muscle test" was performed, where the patients' ability to maintain a flexed position in a selected joint was evaluated. The resistance created by the patient against the tester's pressure was monitored. Being in touch with healthful or unhealthful chemical substances may, according to the kinesiology literature, increase or decrease this resistance. For testing purposes, the drug was placed onto the patients' skin. The ability of the brachioradial muscle to resist the tester's pressure was determined on a subjective scale (0-100%). The Pearson product-moment correlation coefficient between four variables (total cholesterol value before therapy, total cholesterol value after therapy, difference of total cholesterol values before and after therapy, prior to treatment kinesiology testing) was chosen. A significant correlation between the difference of total cholesterol values before-after and the prior to treatment test was found, as well as a significant correlation between the total cholesterol values after therapy and the prior to treatment kinesiology test.

  2. Prostaglandin E2 Indicates Therapeutic Efficacy of Mesenchymal Stem Cells in Experimental Traumatic Brain Injury.

    Science.gov (United States)

    Kota, Daniel J; Prabhakara, Karthik S; Toledano-Furman, Naama; Bhattarai, Deepa; Chen, Qingzheng; DiCarlo, Bryan; Smith, Philippa; Triolo, Fabio; Wenzel, Pamela L; Cox, Charles S; Olson, Scott D

    2017-05-01

    Traumatic brain injury (TBI) is soon predicted to become the third leading cause of death and disability worldwide. After the primary injury, a complex set of secondary injuries develops hours and days later with prolonged neuroinflammation playing a key role. TBI and other inflammatory conditions are currently being treated in preclinical and clinical trials by a number of cellular therapies. Mesenchymal stem cells (MSC) are of great interest due to their widespread usage, safety, and relative ease to isolate and culture. However, there has been a wide range in efficacy reported using MSC clinically and in preclinical models, likely due to differences in cell preparations and a significant amount of donor variability. In this study, we seek to find a correlation between in vitro activity and in vivo efficacy. We designed assays to explore the responsiveness of MSC to immunological cues to address the immunomodulatory properties of MSC, one of their primary modes of therapeutic activity in TBI. Our results showed intrinsic differences in the immunomodulatory capacity of MSC preparations from different bone marrow and amniotic fluid donors. This difference mirrored the therapeutic capacity of the MSC in an experimental model of TBI, an effect confirmed using siRNA knockdown of COX2 followed by overexpressing COX2. Among the immunomodulatory factors assessed, the therapeutic benefit correlated with the secretion of prostaglandin E2 (PGE2 ) by MSC prior to treatment, suggesting that measurement of PGE2 could be a very useful potency marker to create an index of predicted efficacy for preparations of MSC to treat TBI. Stem Cells 2017;35:1416-1430. © 2017 AlphaMed Press.

  3. Efficacy of continuous wear PureVision contact lenses for therapeutic use.

    Science.gov (United States)

    Arora, Ritu; Jain, Shailley; Monga, Sumit; Narayanan, Raja; Raina, Usha Kaul; Mehta, Dinesh Kumar

    2004-03-01

    To evaluate the Bausch and Lomb PureVision contact lens as continuous wear contact lens for therapeutic and medical indications in a prospective open-ended non-randomized trial. Patients who required therapeutic contact lens wear for various indications such as pain relief, corneal protection, persistent epithelial defects, corneal perforation and chemical burns were fitted with PureVision continuous wear contact lenses (balafilcon A, 36% water content). Success or failure of specific treatment indication was assessed in each case with evaluation of ocular and lens related complications. 30 eyes of 28 patients were fitted with PureVision continuous wear contact lenses. A successful fit was seen in 27 of 30 eyes with therapeutic success in 26 of 30 eyes. However, all patients reported symptomatic relief. Duration of lens use ranged from 3 days to 3 months. Dry eye was the most frequent cause of contact lens associated therapeutic failure. Complications included lens loss (two eyes), tight lens (one eye) and infective keratitis (two eyes). PureVision contact lenses were found to be safe and efficacious for continuous wear therapeutic use to a maximum of 90 days. The contact lens was also easier to handle by virtue of its resilient nature. There were no significant corneal complications of hypoxia, i.e. corneal oedema. Lens losses and deposits were minimal. The lens performance and fitting characteristics compares favorably with previous therapeutic lenses used by the investigators. This new lens may be considered as a safe and effective alternative for use as bandage contact lens.

  4. Enhanced Therapeutic Efficacy of iRGD-Conjugated Crosslinked Multilayer Liposomes for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yarong Liu

    2013-01-01

    Full Text Available Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression.

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

    Directory of Open Access Journals (Sweden)

    Brandes Ralf P

    2011-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Jibril Mohammed Nuhu, MSc

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Jennifer C Alexander

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

  8. Fibrinolytic Enzyme Cotherapy Improves Tumor Perfusion and Therapeutic Efficacy of Anticancer Nanomedicine.

    Science.gov (United States)

    Kirtane, Ameya R; Sadhukha, Tanmoy; Kim, Hyunjoon; Khanna, Vidhi; Koniar, Brenda; Panyam, Jayanth

    2017-03-15

    Elevated interstitial fluid pressure and solid stress within tumors contribute to poor intratumoral distribution of nanomedicine. In this study, we hypothesized that the presence of fibrin in tumor extracellular matrix contributes to hindered intratumoral distribution of nanocarriers and that this can be overcome through the use of a fibrinolytic enzyme such as tissue plasminogen activator (tPA). Analysis of fibrin expression in human tumor biopsies showed significant fibrin staining in nearly all tumor types evaluated. However, staining was heterogeneous across and within tumor types. We determined the effect of fibrin on the diffusion, intratumoral distribution, and therapeutic efficacy of nanocarriers. Diffusivity of nanocarriers in fibrin matrices was limited and could be improved significantly by coincubation with tPA. In vivo, coadministration of tPA improved the anticancer efficacy of nanoparticle-encapsulated paclitaxel in subcutaneous syngeneic mouse melanoma and orthotopic xenograft lung cancer models. Furthermore, treatment with tPA led to decompression of blood vessels and improved tumor perfusion. Cotreatment with tPA resulted in greater intratumoral penetration of a model nanocarrier (Doxil), leading to enhanced availability of the drug in the tumor core. Fibrinolytics such as tPA are already approved for other indications. Fibrinolytic cotherapy is therefore a rapidly translatable strategy for improving therapeutic effectiveness of anticancer nanomedicine. Cancer Res; 77(6); 1465-75. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. Alteration of therapeutic efficacy of lipid microspheres incorporating prostaglandin E1 by mixing with aqueous solution.

    Science.gov (United States)

    Komori, Yukiko; Aiba, Tetsuya; Kushima, Miki; Kawasaki, Hiromu; Kurosaki, Yuji

    2007-04-01

    To clarify whether the therapeutic efficacy of lipid microspheres incorporating prostaglandin E(1) (lipo-PGE(1)) is altered when mixed and coinfused with clinical solutions, the original lipo-PGE(1) solution (20 microg/mL) was mixed with three clinical infusion solutions: 0.9% sodium chloride solution, Hartmann's solution, and fat emulsion for parenteral nutrition. These diluted lipo-PGE(1) (2 microg/mL) solutions were administered to rats, and their hemodynamic and antiplatelet effects were examined. Peripheral blood flow was increased by 76 +/- 4% from the control level when the lipo-PGE(1) solution diluted with the fat emulsion was administered, while it was increased by 43 +/- 6% and 36 +/- 7%, respectively, when the lipo-PGE(1) solutions diluted with 0.9% sodium chloride and Hartmann's solution were administered. As for the antiplatelet effects of the lipo-PGE(1) solutions, the progression of digit gangrene in thromboangiitis obliterans (TAO) rats was significantly suppressed by the administration of lipo-PGE(1) solution diluted with the fat emulsion, but it was not suppressed by lipo-PGE(1) solution diluted with 0.9% sodium chloride. These findings indicate that the therapeutic efficacy of lipo-PGE(1) is decreased when it is mixed with an aqueous solution such as 0.9% sodium chloride. (c) 2007 Wiley-Liss, Inc.

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

    Science.gov (United States)

    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.

  11. The indirect effect of the therapeutic alliance and alcohol abstinence self-efficacy on alcohol use and alcohol-related problems in Project MATCH.

    Science.gov (United States)

    Maisto, Stephen A; Roos, Corey R; O'Sickey, Anthony J; Kirouac, Megan; Connors, Gerard J; Tonigan, J Scott; Witkiewitz, Katie

    2015-03-01

    Empirical literature indicates that the therapeutic alliance explains a modest but reliable proportion of variance in predicting alcohol-related outcomes among individuals in treatment for alcohol use disorders (AUDs). Hartzler and colleagues (2011) showed in the COMBINE data set that alcohol abstinence self-efficacy is a potentially important statistical mediator of the relationship between the alliance and client outcomes. The purpose of this study was to replicate this finding in the Project MATCH data set. We used total alliance ratings on the Working Alliance Inventory and tested both client and therapist ratings in mediation analyses. We found that posttreatment self-efficacy accounted for the effect of therapist and client ratings of alliance (measured at session 2) on posttreatment drinking outcomes (drinks per drinking day and alcohol-related problems). In addition, we found a moderation effect of treatment, such that the association between the client's rating of the alliance and self-efficacy changes was positive for individuals in the cognitive behavioral treatment group but negative for those receiving motivation enhancement or Twelve-Step Facilitation. This study reaffirms the importance of the therapeutic alliance and self-efficacy in predicting AUD outcomes. Future research should examine changes in the therapeutic alliance throughout treatment and how these changes are related to self-efficacy and AUD treatment outcomes over time. Copyright © 2015 by the Research Society on Alcoholism.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Shimizu N

    2013-05-01

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

  14. A New Preclinical Paradigm for Testing Anti-Aging Therapeutics.

    Science.gov (United States)

    Ladiges, Warren; Snyder, Jessica M; Wilkinson, Erby; Imai, Denise M; Snider, Tim; Ge, Xuan; Ciol, Marcia; Pettan-Brewer, Christina; Pillai, Smitha P S; Morton, John; Quarles, Ellen; Rabinovitch, Peter; Niedernhofer, Laura; Liggitt, Denny

    2017-06-01

    Testing drugs for anti-aging effects has historically been conducted in mouse life-span studies, but are costly and time consuming, and more importantly, difficult to recapitulate in humans. In addition, life-span studies in mice are not well suited to testing drug combinations that target multiple factors involved in aging. Additional paradigms for testing therapeutics aimed at slowing aging are needed. A new paradigm, designated as the Geropathology Grading Platform (GGP), is based on a standardized set of guidelines developed to detect the presence or absence of low-impact histopathological lesions and to determine the level of severity of high-impact lesions in organs from aged mice. The GGP generates a numerical score for each age-related lesion in an organ, summed for total lesions, and averaged over multiple mice to obtain a composite lesion score (CLS). Preliminary studies show that the platform generates CLSs that increase with the age of mice in an organ-dependent manner. The CLSs are sensitive enough to detect changes elicited by interventions that extend mouse life span, and thus help validate the GGP as a novel tool to measure biological aging. While currently optimized for mice, the GGP could be adapted to any preclinical animal model. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

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

  16. Predicting therapeutic nanomedicine efficacy using a companion magnetic resonance imaging nanoparticle.

    Science.gov (United States)

    Miller, Miles A; Gadde, Suresh; Pfirschke, Christina; Engblom, Camilla; Sprachman, Melissa M; Kohler, Rainer H; Yang, Katherine S; Laughney, Ashley M; Wojtkiewicz, Gregory; Kamaly, Nazila; Bhonagiri, Sushma; Pittet, Mikael J; Farokhzad, Omid C; Weissleder, Ralph

    2015-11-18

    Therapeutic nanoparticles (TNPs) have shown heterogeneous responses in human clinical trials, raising questions of whether imaging should be used to identify patients with a higher likelihood of NP accumulation and thus therapeutic response. Despite extensive debate about the enhanced permeability and retention (EPR) effect in tumors, it is increasingly clear that EPR is extremely variable; yet, little experimental data exist to predict the clinical utility of EPR and its influence on TNP efficacy. We hypothesized that a 30-nm magnetic NP (MNP) in clinical use could predict colocalization of TNPs by magnetic resonance imaging (MRI). To this end, we performed single-cell resolution imaging of fluorescently labeled MNPs and TNPs and studied their intratumoral distribution in mice. MNPs circulated in the tumor microvasculature and demonstrated sustained uptake into cells of the tumor microenvironment within minutes. MNPs could predictably demonstrate areas of colocalization for a model TNP, poly(d,l-lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG), within the tumor microenvironment with >85% accuracy and circulating within the microvasculature with >95% accuracy, despite their markedly different sizes and compositions. Computational analysis of NP transport enabled predictive modeling of TNP distribution based on imaging data and identified key parameters governing intratumoral NP accumulation and macrophage uptake. Finally, MRI accurately predicted initial treatment response and drug accumulation in a preclinical efficacy study using a paclitaxel-encapsulated NP in tumor-bearing mice. These approaches yield valuable insight into the in vivo kinetics of NP distribution and suggest that clinically relevant imaging modalities and agents can be used to select patients with high EPR for treatment with TNPs. Copyright © 2015, American Association for the Advancement of Science.

  17. 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

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

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

    2016-06-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. 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.

  20. Changes in cytokine profile may predict therapeutic efficacy of infliximab in patients with ulcerative colitis.

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    Sato, Shoko; Chiba, Toshimi; Nakamura, Shotaro; Matsumoto, Takayuki

    2015-10-01

    Infliximab is an established therapy for ulcerative colitis (UC). The aim of this study was to examine various serum cytokine levels and to identify possible markers predictive of therapeutic efficacy of infliximab for UC patients. Twenty-one patients with moderately active UC were given intravenous infliximab (5 mg/kg) at 0, 2, and 6 weeks as induction therapy. The serum levels of 17 cytokines were determined using a Bio-Plex suspension array system before and 8 weeks after induction therapy. Partial Mayo score (PMS) and serum C-reactive protein levels were used for the determination of clinical activities at 0 and 8 weeks after the treatment. The overall therapeutic effect was determined at 26 weeks according to the PMS. The median value of the PMS decreased significantly 8 weeks after the treatment (from 6 to 1.5, P infliximab, while IL-6 at 8 weeks after induction therapy may be predictive of subsequent response to infliximab. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  1. Further Validation of the Norwegian Self-Efficacy for Therapeutic Mode Use

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    Victoria C. Ritter

    2017-01-01

    Full Text Available Background. The Intentional Relationship Model (IRM proposes six therapeutic modes as ways of relating to clients. The Norwegian self-efficacy for therapeutic mode use (N-SETMU was found to have a one-component structure. However, its items reflect abstract concepts rather than concrete behaviors. Aim. To validate further the N-SETMU by linking its items to the Norwegian client assessment of modes (N-CAM, with 30 items constituting six scales (linked to each mode, possessing concrete, behavioral content. Methods. Occupational therapy students (n=111 completed the N-SETMU and the N-CAM derived items, along with sociodemographic information. Component structure was analyzed with Principal Components Analysis (PCA, internal consistency of scales with Cronbach’s α, and associations between scale scores with Pearson’s r. Results. All items on all N-CAM derived scales loaded on one latent component, except one item related to problem-solving. After removing this item, the scale functioned appropriately. Cronbach’s α for all N-CAM derived scales ranged 0.88–0.94, and the associations between the N-CAM derived scales and the corresponding N-SETMU items ranged between 0.60 (advocating and 0.79 (encouraging. Conclusions. In view of the strong associations between the concrete, N-CAM derived scales and the abstract N-SETMU items, this study supports the concurrent validity of the N-SETMU.

  2. Interaction with therapeutic soft contact lenses affects the intraocular efficacy of tropicamide and latanoprost in dogs.

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    Hatzav, M; Bdolah-Abram, T; Ofri, R

    2016-04-01

    Therapeutic soft contact lenses (TSCLs) are frequently used to support or protect the cornea during healing. Our aim was to quantitatively evaluate the efficacy of topical medications in TSCL-fitted dogs and determine whether it is affected by the presence of TSCLs. In Phase I, pupil diameter was measured in eyes treated with tropicamide and in eyes covered with TSCLs and then treated with tropicamide, with 1-week intervals between sessions. In Phase II, intraocular pressure (IOP) was measured in uncovered and TSCL-covered eyes treated with latanoprost, with 1-week intervals between sessions. Tropicamide caused significant mydriasis in both uncovered and TSCL-covered eyes (P = 0.005). On the other hand, latanoprost caused a significant decrease in IOP when applied to uncovered eyes (P = 0.002), but had no significant effect on IOP when applied to TSCL-covered eyes (P = 0.7). As we used the same dogs and identical TSCLs throughout the study, we conclude that the different outcomes of the two drugs are due to properties of the drugs themselves, or their formulations, affecting their interaction with the TSCLs. The clinical efficacy of topical drugs applied to TSCL-covered eyes may have to be determined for each drug and/or formulation. © 2015 John Wiley & Sons Ltd.

  3. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma.

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    Jessica M Stiles

    Full Text Available Therapeutic targeting of the beta-adrenergic receptors has recently shown remarkable efficacy in the treatment of benign vascular tumors such as infantile hemangiomas. As infantile hemangiomas are reported to express high levels of beta adrenergic receptors, we examined the expression of these receptors on more aggressive vascular tumors such as hemangioendotheliomas and angiosarcomas, revealing beta 1, 2, and 3 receptors were indeed present and therefore aggressive vascular tumors may similarly show increased susceptibility to the inhibitory effects of beta blockade. Using a panel of hemangioendothelioma and angiosarcoma cell lines, we demonstrate that beta adrenergic inhibition blocks cell proliferation and induces apoptosis in a dose dependent manner. Beta blockade is selective for vascular tumor cells over normal endothelial cells and synergistically effective when combined with standard chemotherapeutic or cytotoxic agents. We demonstrate that inhibition of beta adrenergic signaling induces large scale changes in the global gene expression patterns of vascular tumors, including alterations in the expression of established cell cycle and apoptotic regulators. Using in vivo tumor models we demonstrate that beta blockade shows remarkable efficacy as a single agent in reducing the growth of angiosarcoma tumors. In summary, these experiments demonstrate the selective cytotoxicity and tumor suppressive ability of beta adrenergic inhibition on malignant vascular tumors and have laid the groundwork for a promising treatment of angiosarcomas in humans.

  4. Microgravity access as a means for testing therapeutic pharmaceutics

    Science.gov (United States)

    Zimmerman, Robert J.; Simske, Steven J.

    1995-01-01

    Spaceflight results in a unique combination of physiological effects. Immune, musculoskeletal, cardiovascular, renal and other physiological systems are deleteriously affected by the microgravity environment. Many of these effects are analogous to diseases that afflict people on earth; for instance, immunosuppressive disorders and osteoporosis. Chiron Corporation (Emeryville, CA) is interested in using spaceflight as a testing ground for its unique therapeutic pharmaceutics. On STS-60 (Feb. 1994), Chiron, heading up a consortium managed by its CCDS (Center for the Commercial Development of Space) partner Bioserve Space Technologies, investigated the effects of its recombinant interleukin-2 (IL-2) pharmaceutic on preventing the immune system suppression induced that mimicked spaceflight (tail suspension). The recombinant, pegulated IL-2 largely prevented the deleterious effects of spaceflight and particularly suspension on the development of macrophages and the spleen. Based on these findings, Chiron hopes to expand its original market for Il-2 to include veterinary applications. In future missions, Chiron hopes to further explore the physiological effects of IL-2 in preventing the spaceflight effects (STS-63), and to use spaceflight access as a means for testing drugs which may be useful for the treatment of other diseases (e.g., M-CSF for osteoporosis). Spaceflight access has provided Chiron with new applications and new approaches for determining the effects of their pharmaceutics.

  5. Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells

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    Lei-qing Li

    2013-01-01

    Full Text Available Although the combination of herpes simplex virus type 1 (HSV-1 thymidine kinase (TK with ganciclovir (GCV has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5-dimethylthiahiazo-(-z-y1-3,5-di-phenytetrazoliumromide (MTT colorimetric assay and Hoechst-propidium iodide (PI staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting.

  6. Biochemical changes associated with ascorbic acid–cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice

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    Amenla Longchar

    2015-01-01

    Full Text Available Cisplatin is one of the well-established anticancer drugs being used against a wide spectrum of cancers. However, full therapeutic efficacy of the drug is limited due to development of various toxicities in the host. This study examines the comparative therapeutic effectiveness and toxicities of cisplatin alone and in combination of dietary ascorbic acid (AA in ascites Dalton's lymphoma-bearing mice. The findings show that the combination treatment of mice with ascorbic acid plus cisplatin has much better therapeutic efficacy against murine ascites Dalton's lymphoma (DL in comparison to cisplatin alone and this may involve a decrease in reduced glutathione (GSH, catalase activity and increased lipid peroxidation (LPO in Dalton's lymphoma tumor cells. At the same time, combination treatment indicates a protective role of ascorbic acid against cisplatin-induced tissue toxicities (side effects in the hosts. Cisplatin-induced histopathological changes in liver, kidney and testes were decreased after combination treatment. The analysis of renal function test (RFT, liver function test (LFT and sperm abnormalities also suggest an improvement in these parameters after combination treatment. Therefore, it may be concluded that the increased GSH level, catalase activity and decreased LPO in the tissues, i.e., liver, kidney and testes after combination treatment may be involved in its protective ability against cisplatin-induced tissue toxicities in the host.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

    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

  9. Lactoferrin nanoparticle mediated targeted delivery of 5-fluorouracil for enhanced therapeutic efficacy.

    Science.gov (United States)

    Kumari, Sonali; Kondapi, Anand K

    2017-02-01

    Malignant melanoma is an aggressive form of skin cancer with high mortality rates. Common treatments for malignant melanoma involve a combination of radiotherapy and chemotherapy with fluorouracil (5-FU). A major challenge with melanoma treatment is active resistance to chemotherapeutic drugs. Superior treatment outcome lies on balance involving optimum therapeutic doses and the side effects associated with dose escalation. The study aimed to efficiently entrap 5-FU in lactoferrin nanoparticles (LfNPs) in an attempt to enhance its therapeutic efficacy. 5-FU loaded lactoferrin nanoparticles (5-FU-LfNPs) were prepared by sol-oil method with a narrow size distribution of 150±20nm 5-FU-LfNPs exhibits high encapsulation efficiency (64±2.3%) and increased storage stability at 4°C. Competitive ligand binding and lysosomal colocalization studies suggested a receptor mediated uptake for LfNPs internalization in B16F10 cells. Moreover, 5-FU-LfNPs show a pH dependent drug release similar to endosomal pH (pH 5 and 6). In addition compared to free 5-FU, 5-FU- LfNPs showed a higher intracellular uptake, prolonged retention and improved cytotoxicity (2.7-fold) in melanoma cells (B16F10). To conclude, LfNPs represent a superior nano-carrier for the targeted delivery of 5-FU in melanoma cells intended for the efficient treatment of melanoma though detailed in vivo investigations are warranted. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection.

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    van Niekerk, Gustav; Hattingh, Suzèl M; Engelbrecht, Anna-Mart

    2016-01-01

    Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to upregulate autophagy, an evolutionarily conserved catabolic process that is upregulated in response to various cell stressors. Here, we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. First, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts.

  11. Online-mediated syphilis testing: Feasibility, efficacy, and usage

    NARCIS (Netherlands)

    Koekenbier, Rik H.; Davidovich, Udi; van Leent, Edwin J. M.; Thiesbrummel, Harold F. J.; Fennema, Han S. A.

    2008-01-01

    Objectives: To determine the feasibility and efficacy of an online-mediated syphilis screening among men who have sex with men. Methods: We developed a Web site that offered information about syphilis and motivated users to download a referral letter with which they could test for syphilis in a

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

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    Dev Vas

    2009-05-01

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

  13. 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.)

  14. Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis.

    Science.gov (United States)

    Kreisel, W; Köchling, G; von Schilling, C; Azemar, M; Kurzweil, B; Dölken, G; Lindemann, A; Blum, U; Windfuhr, M; Müller, J

    1991-01-01

    We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.

  15. Free radicals and other reactive oxygen metabolites: clinical relevance and the therapeutic efficacy of antioxidant therapy.

    Science.gov (United States)

    Bulkley, G B

    1993-05-01

    As in any new field, justifiable enthusiasm for the potential for antioxidant therapy has led to hyperbole, hastily designed, poorly conceived clinical trials, and premature reporting of uncontrolled, anecdotal indicators of efficacy that have not held up when subjected to close scrutiny or more careful, controlled trial design. This tendency has been augmented by strong pressure for early positive results from a few, but not most, members of the pharmaceutical industry and by a few clinicians in highly competitive fields who were anxious not to be left behind. The sobering reality of negative or, even worse, indeterminate clinical trials has culled the field and educated those that remain. As a result, we are beginning to see the publication of quite promising results from large, well-controlled, carefully designed clinical studies, many, but not all, of which are quite promising. This has been associated with a much better understanding of the basic mechanism of free radical-mediated human disease, without which further substantial progress would be quite limited. Because the manipulation of oxidant-mediated tissue injury represents treating disease at its most basic level, the therapeutic potential of this approach remains not only promising but exciting.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Improving gastric transit, gastrointestinal persistence and therapeutic efficacy of the probiotic strain Bifidobacterium breve UCC2003.

    Science.gov (United States)

    Sheehan, Vivien M; Sleator, Roy D; Hill, Colin; Fitzgerald, Gerald F

    2007-10-01

    Given the increasing commercial and clinical relevance of probiotic cultures, improving their stress tolerance profile and ability to overcome the physiological defences of the host is an important biological goal. In order to reach the gastrointestinal tract in sufficient numbers to exert a therapeutic effect, probiotic bacteria must resist the deleterious actions of low pH, elevated osmolarity and bile salts. Cloning the listerial betaine uptake system, BetL, into the probiotic strain Bifidobacterium breve UCC2003 significantly improved probiotic tolerance to gastric juice and conditions of elevated osmolarity mimicking the gut environment. Furthermore, whilst stable colonization of the murine intestine was achieved by oral administration of B. breve UCC2003, strains harbouring BetL were recovered at significantly higher levels in the faeces, intestines and caecum of inoculated animals. Finally, in addition to improved gastric transit and intestinal persistence, this approach improved the clinical efficacy of the probiotic culture: mice fed B. breve UCC2003-BetL(+) exhibited significantly lower levels of systemic infection compared to the control strain following oral inoculation with Listeria monocytogenes.

  18. Intrathecal baclofen therapy for adults with spinal spasticity: therapeutic efficacy and effect on hospital admissions.

    Science.gov (United States)

    Nance, P; Schryvers, O; Schmidt, B; Dubo, H; Loveridge, B; Fewer, D

    1995-02-01

    A prospective trial to demonstrate the efficacy of intrathecal baclofen therapy by implanted pump for adults with spasticity due to spinal cord injury or multiple sclerosis was initiated in our hospital. Of the 140 patients assessed, 7 met the following criteria for inclusion in the study: a modified Ashworth score > 3, a spasm frequency score > 2, and an inadequate response to oral anti-spasticity drugs, (i.e., baclofen, clonidine and cyproheptadine). All patients responded to intrathecal bolus injection of baclofen in the double blind, placebo-controlled screening phase (mean bolus dose = 42.8 micrograms). Programmable Medtronic pumps were implanted in 4 patients while 3 patients received non-programmable Infusaid pumps. Post-implantation, a marked decrease in spasticity occurred with a significant reduction of the Ashworth score (mean = 1.8, p pendulum test. These effects were maintained during a follow-up of 24-41 months (average infusion dose = 218.7 micrograms/day). The gross cost-savings due to reduced hospitalizations related to spasticity was calculated by comparing the cost for the two year period before pump implantation to the same period after treatment for 6 of the 7 patients. The cost of in-hospital implantation as well as the cost of the pumps were deducted from the gross savings. There was a net cost-saving of $153,120. Our findings agree with the reported efficacy and safety of intrathecal baclofen treatment, and illustrate the cost-effectiveness of this treatment.

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

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  3. Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

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    Soon Ae Kim

    2011-04-01

    Full Text Available BackgroundSitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4 inhibitor that increases blood levels of active glucagon-like peptide (GLP-1 and glucose-dependent insulinotrophic polypeptide (GIP, resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM, its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.MethodsWe obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c and fasting plasma glucose (ΔFPG were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.ResultsWe classified 81% of the subjects (204 out of 251 as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01 and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03 than the non-responder group.ConclusionIn Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

  4. Efficacy of different therapeutic regimens for acute foot rot in adult sheep

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    Mohammad Moin Ansari

    2014-09-01

    Full Text Available In this study, efficacies of different therapeutic regimens along with 10% zinc-sulfate footbath for the treatment of acute foot rot in adult sheep were evaluated. The research work conducted on the adult sheep (n=104 of both sexes which were presented to the Teaching Veterinary Clinical Complex during April 2013 to May 2014. Foot rot was confirmed based on clinical and physical examinations. The sheep were divided into four equal groups; G-I, G-II, G-III, and G-IV. The animals of the G-I, II and IV were treated with a mixture of amoxicillin and cloxacillin at 15 mg/kg body weight (b.wt. through intramuscular (IM route, oxytetracycline at 20 mg/kg b.wt., IM, and enrofloxacin at 5 mg/kg b.wt., IM, respectively. The animals of G-III were treated with gamma benzene hexachloride cream. Along with the above treatments, all four groups were given footbath with 10% zinc-sulfate. Mean recovery time (days was recorded as lowest in G-II (3.83±0.64 followed by G-I (4.17±0.31, G-IV (4.38±0.0.79 and G-III (5.67±0.98, respectively. The mean±SE values of rectal temperature and ruminal motility that were recorded before and after the treatment showed significant (p<0.05 differences. In conclusion, administration of parenteral antibiotics in combination with footbath was highly effective to treat combination with footbath was highly effective to treat the acute foot rot in sheep.

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

    Directory of Open Access Journals (Sweden)

    Jagannathan NR

    2008-09-01

    Full Text Available Abstract 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    Monir Moradzadeh Khiavi

    2015-06-01

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

  8. The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer.

    Science.gov (United States)

    Meidenbauer, Joshua J; Mukherjee, Purna; Seyfried, Thomas N

    2015-01-01

    Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy. A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI). The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.

  9. Ginsenoside rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window.

    Science.gov (United States)

    Ye, Ruidong; Kong, Xiangwei; Yang, Qianzi; Zhang, Yunxia; Han, Junliang; Li, Ping; Xiong, Lize; Zhao, Gang

    2011-07-01

    Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has been demonstrated to protect against ischemic cerebral damage in vitro and in vivo. In this study, we aimed to further define the preclinical characteristics of Rd. We show that Rd passes the intact blood-brain barrier and exerts protection in both transient and permanent middle cerebral artery occlusion (MCAO) in rats. In the dose-response study, Rd (10-50 mg/Kg) significantly reduced the infarct volume on postoperative days (PODs) 1, 3, and 7. This protection was associated with an improved neurological outcome for as many as 6 weeks after transient MCAO, as assessed by modified neurological severity score, modified sticky-tape test, and corner test. For comparison, Rd was significantly more effective than edaravone and slightly more effective than N-tert-butyl-alpha-phenylnitrone (PBN). In the therapeutic window study, Rd exhibited remarkable neuroprotection, even when administered for as many as 4 h after the recirculation of transient MCAO or after the onset of permanent MCAO. Furthermore, in female rats or 16-month-old male rats, the salutary effects of Rd were also observed. These findings suggest Rd is a promising neuroprotectant and provide support for future clinical studies to confirm whether Rd is beneficial in ischemic stroke.

  10. Carbon Monoxide in Exhaled Breath Testing and Therapeutics

    Science.gov (United States)

    Ryter, Stefan W.; Choi, Augustine M.K.

    2013-01-01

    Carbon monoxide (CO), a low molecular weight gas, is a ubiquitous environmental product of organic combustion, which is also produced endogenously in the body, as the byproduct of heme metabolism. CO binds to hemoglobin, resulting in decreased oxygen delivery to bodily tissues at toxicological concentrations. At physiological concentrations, CO may have endogenous roles as a potential signaling mediator in vascular function and cellular homeostasis. Exhaled CO (eCO), similar to exhaled nitric oxide (eNO), has been evaluated as a candidate breath biomarker of pathophysiological states, including smoking status, and inflammatory diseases of the lung and other organs. eCO values have been evaluated as potential indicators of inflammation in asthma, stable COPD and exacerbations, cystic fibrosis, lung cancer, or during surgery or critical care. The utility of eCO as a marker of inflammation, and potential diagnostic value remains incompletely characterized. Among other candidate “medicinal gases” with therapeutic potential, (e.g., NO and H2S), CO has been shown to act as an effective anti-inflammatory agent in preclinical animal models of inflammatory disease, acute lung injury, sepsis, ischemia/reperfusion injury and organ graft rejection. Current and future clinical trials will evaluate the clinical applicability of this gas as a biomarker and/or therapeutic in human disease. PMID:23446063

  11. Carbon monoxide in exhaled breath testing and therapeutics.

    Science.gov (United States)

    Ryter, Stefan W; Choi, Augustine M K

    2013-03-01

    Carbon monoxide (CO), a low molecular weight gas, is a ubiquitous environmental product of organic combustion, which is also produced endogenously in the body, as the byproduct of heme metabolism. CO binds to hemoglobin, resulting in decreased oxygen delivery to bodily tissues at toxicological concentrations. At physiological concentrations, CO may have endogenous roles as a potential signaling mediator in vascular function and cellular homeostasis. Exhaled CO (eCO), similar to exhaled nitric oxide (eNO), has been evaluated as a candidate breath biomarker of pathophysiological states, including smoking status, and inflammatory diseases of the lung and other organs. eCO values have been evaluated as potential indicators of inflammation in asthma, stable COPD and exacerbations, cystic fibrosis, lung cancer, or during surgery or critical care. The utility of eCO as a marker of inflammation and its potential diagnostic value remain incompletely characterized. Among other candidate 'medicinal gases' with therapeutic potential, (e.g., NO and H2S), CO has been shown to act as an effective anti-inflammatory agent in preclinical animal models of inflammatory disease, acute lung injury, sepsis, ischemia/reperfusion injury and organ graft rejection. Current and future clinical trials will evaluate the clinical applicability of this gas as a biomarker and/or therapeutic in human disease.

  12. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  14. Assessing the therapeutic efficacy of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig

    Science.gov (United States)

    Snider, Thomas H.; Wilhelm, Christina M.; Babin, Michael C.; Platoff, Gennady E.; Yeung, David T.

    2016-01-01

    Given the rapid onset of symptoms from intoxication by organophosphate (OP) compounds, a quick-acting, efficacious therapeutic regimen is needed. A primary component of anti-OP therapy is an oxime reactivator to rescue OP-inhibited acetylcholinesterases. Male guinea pigs, clipped of hair, received neat applications of either VR, VX, parathion, or phorate oxon (PHO) at the 85th percentile lethal dose, and, beginning with presentation of toxicosis, received the human equivalent dose therapy by intramuscular injection with two additional follow-on treatments at 3-hr intervals. Each therapy consisted of atropine free base at 0.4 mg/kg followed by one of eight candidate oximes. Lethality rates were obtained at 24 hr after VR, VX and PHO challenges, and at 48 hr after challenge with parathion. Lethality rates among symptomatic, oxime-treated groups were compared with that of positive control (OP-challenged and atropine-only treated) guinea pigs composited across the test days. Significant (p ≤ 0.05) protective therapy was afforded by 1,1-methylene bis(4(hydroxyimino- methyl)pyridinium) dimethanesulfonate (MMB4 DMS) against challenges of VR (p ≤ 0.001) and VX (p ≤ 0.05). Lethal effects of VX were also significantly (p ≤ 0.05) mitigated by treatments with oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1-yl] methoxymethyl]pyridin-4-ylidene]methyl]azanium dichloride (obidoxime Cl2) and 1-(((4-(aminocarbonyl) pyridinio)methoxy)methyl)-2,4-bis((hydroxyimino)methyl)pyridinium dimethanesulfonate (HLö-7 DMS). Against parathion, significant protective therapy was afforded by obidoxime dichloride (p ≤ 0.001) and 1,1′-propane-1,3-diylbis{4-[(E)-(hydroxyimino)methyl]pyridinium} dibromide (TMB-4, p ≤ 0.01). None of the oximes evaluated was therapeutically effective against PHO. Across the spectrum of OP chemicals tested, the oximes that offered the highest level of therapy were MMB4 DMS and obidoxime dichloride. PMID:26558457

  15. The Therapeutic Efficacy of Environmental Enrichment and Methylphenidate Alone and in Combination after Controlled Cortical Impact Injury.

    Science.gov (United States)

    Leary, Jacob B; Bondi, Corina O; LaPorte, Megan J; Carlson, Lauren J; Radabaugh, Hannah L; Cheng, Jeffrey P; Kline, Anthony E

    2017-01-15

    Environmental enrichment (EE) and methylphenidate (MPH) independently confer significant benefit to behavioral recovery after controlled cortical impact (CCI) injury. Given that combinational therapies may be more clinically translatable than monotherapies, the aim of the current study was to test the hypothesis that a combined treatment regimen of EE and MPH would provide greater therapeutic efficacy than either one alone. Anesthetized adult male rats received either a CCI of moderate severity or sham injury and were then randomly assigned to EE or standard (STD) housing where they received either intraperitoneal (ip) MPH (5 mg/kg) or vehicle (VEH; 1.0 mL/kg; ip) beginning 24 h after injury and once daily for 19 days. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. No differences were observed in sham controls regardless of treatments, and thus their data were pooled. The traumatic brain injury (TBI)+EE+VEH and TBI+EE+MPH groups exhibited enhanced beam balance and beam walk performance relative to the TBI+STD+VEH group (p  0.05). No effect of MPH treatment alone was observed in either motor task. In contrast, MPH improved spatial learning and memory when presented alone and also when combined with EE relative to VEH-treated STD controls (p  0.05). These data replicate previous findings that both EE and MPH confer cognitive benefits after TBI and extend the findings by revealing that combining EE and MPH does not produce effects greater than either treatment alone, which does not support the hypothesis. The lack of an additive effect may be because of the robustness of the EE.

  16. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models.

    Science.gov (United States)

    Hengst, Jeremy A; Dick, Taryn E; Sharma, Arati; Doi, Kenichiro; Hegde, Shailaja; Tan, Su-Fern; Geffert, Laura M; Fox, Todd E; Sharma, Arun K; Desai, Dhimant; Amin, Shantu; Kester, Mark; Loughran, Thomas P; Paulson, Robert F; Claxton, David F; Wang, Hong-Gang; Yun, Jong K

    2017-01-01

    To further characterize the selectivity, mechanism-of-action and therapeutic efficacy of the novel small molecule inhibitor, SKI-178. Using the state-of-the-art Cellular Thermal Shift Assay (CETSA) technique to detect "direct target engagement" of proteins intact cells, in vitro and in vivo assays, pharmacological assays and multiple mouse models of acute myeloid leukemia (AML). Herein, we demonstrate that SKI-178 directly target engages both Sphingosine Kinase 1 and 2. We also present evidence that, in addition to its actions as a Sphingosine Kinase Inhibitor, SKI-178 functions as a microtubule network disrupting agent both in vitro and in intact cells. Interestingly, we separately demonstrate that simultaneous SphK inhibition and microtubule disruption synergistically induces apoptosis in AML cell lines. Furthermore, we demonstrate that SKI-178 is well tolerated in normal healthy mice. Most importantly, we demonstrate that SKI-178 has therapeutic efficacy in several mouse models of AML. SKI-178 is a multi-targeted agent that functions both as an inhibitor of the SphKs as well as a disruptor of the microtubule network. SKI-178 induced apoptosis arises from a synergistic interaction of these two activities. SKI-178 is safe and effective in mouse models of AML, supporting its further development as a multi-targeted anti-cancer therapeutic agent.

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

    Directory of Open Access Journals (Sweden)

    Jeehoon Kang

    2016-11-01

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

  18. MYC-dependent downregulation of telomerase by FLT3 inhibitors is required for their therapeutic efficacy on acute myeloid leukemia.

    Science.gov (United States)

    Zhang, Xiaolu; Li, Bingnan; Yu, Jingya; Dahlström, Jenny; Tran, Anh Nhi; Björkhom, Magnus; Xu, Dawei

    2018-01-01

    The somatic mutation of FLT3 occurs in 30% of acute myeloid leukemia (AML), with the majority of mutations exhibiting internal tandem duplication (ITD). On the other hand, the induction of telomerase reverse transcriptase (hTERT) and the activation of telomerase is a key step in AML development. Here, we sought to determine whether FLT3ITD regulates hTERT expression in AML cells and whether hTERT expression affects FLT3 inhibitors' therapeutic efficacy on AML. FLT3ITD-harboring AML cell lines and primary cells treated with the FLT3 inhibitor PKC412 displayed a rapid decline in the levels of hTERT mRNA and telomerase activity. Moreover, PKC412 inhibited hTERT gene transcription in a c-MYC-dependent manner. The ectopic expression of hTERT significantly attenuated the apoptotic effect of PKC412 on AML cells. Mechanistically, hTERT enhanced the activity of FLT3 downstream effectors or alternative RTK signaling, thereby enhancing AKT phosphorylation, in AML cells treated with PKC412. Collectively, PKC412 downregulates hTERT expression and telomerase activity in a MYC-dependent manner and this effect is required for its optimal anti-AML efficacy, while hTERT over-expression confers AML cells resistance to a targeted therapeutic agent PKC412. These findings suggest that the functional interplay between FLT3ITD and hTERT contributes to the AML pathogenesis and interferes with the efficacy of FLT3ITD-targeted therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

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

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

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    Thomas L. Chenevert

    2002-10-01

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

  2. Efficacy of toltrazuril as a metaphylactic and therapeutic treatment of coccidiosis in first-year grazing calves.

    Science.gov (United States)

    Epe, C; von Samson-Himmelstjerna, G; Wirtherle, N; von der Heyden, V; Welz, C; Beening, J; Radeloff, I; Hellmann, K; Schnieder, T; Krieger, K

    2005-10-01

    A multicentric, placebo-controlled, randomised, blinded and blocked field study was conducted to evaluate the efficacy and safety of toltrazuril (Baycox, Bayer AG, Leverkusen, Germany) in the treatment of coccidiosis in first-year grazing calves naturally infected with Eimeria spp. Three-hundred and thirty-one calves were enrolled in the study and allocated to one of two treatments at a ratio of 1:1. One hundred and sixty-seven animals were treated once orally with 15 mg/kg toltrazuril, and 164 animals served as placebo-treated controls. Two treatment regimes were compared, a metaphylactic (treatment on the day, or 1 day after, turn out) and a therapeutic treatment (4 or 7 days after turn out). During an observation period of 14 days after treatment the animals were clinically examined for diarrhoea and faecal samples were regularly assessed for Eimeria oocysts. Other possible causes of diarrhoea were excluded on the basis of microbiological and virological examination. Animals were predominantly infected with Eimeria alabamensis. Number of days with diarrhoea in animals treated with toltrazuril was significantly lower compared to the placebo-treated group (therapeutic treatment: P=0.0024; metaphylactic treatment: Ptoltrazuril- compared to the placebo-treated animals. Body weight in the toltrazuril-treated animals significantly exceeded that of the placebo-treated animals at the end of the observation period. Mean difference in body weight was higher in the metaphylactic (+7.3 kg) compared to the therapeutic treatment group (+3.4 kg). No adverse reactions were observed. The results indicate that toltrazuril is highly efficacious and safe in the metaphylactic and therapeutic treatment of coccidiosis caused by E. alabamensis in first-year grazing calves.

  3. Transposon-mediated Generation of Cellular and Mouse Models of Splicing Mutations to Assess the Efficacy of snRNA-based Therapeutics

    Directory of Open Access Journals (Sweden)

    Elena Barbon

    2016-01-01

    Full Text Available Disease-causing splicing mutations can be rescued by variants of the U1 small nuclear RNA (U1snRNAs. However, the evaluation of the efficacy and safety of modified U1snRNAs as therapeutic tools is limited by the availability of cellular and animal models specific for a given mutation. Hence, we exploited the hyperactive Sleeping Beauty transposon system (SB100X to integrate human factor IX (hFIX minigenes into genomic DNA in vitro and in vivo. We generated stable HEK293 cell lines and C57BL/6 mice harboring splicing-competent hFIX minigenes either wild type (SChFIX-wt or mutated (SChFIXex5-2C. In both models the SChFIXex5-2C variant, found in patients affected by Hemophilia B, displayed an aberrant splicing pattern characterized by exon 5 skipping. This allowed us to test, for the first time in a genomic DNA context, the efficacy of the snRNA U1-fix9, delivered with an adeno-associated virus (AAV vector. With this approach, we showed rescue of the correct splicing pattern of hFIX mRNA, leading to hFIX protein expression. These data validate the SB100X as a versatile tool to quickly generate models of human genetic mutations, to study their effect in a stable DNA context and to assess mutation-targeted therapeutic strategies.

  4. Immediate skin responses to laser and light treatments: Therapeutic endpoints: How to obtain efficacy.

    Science.gov (United States)

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Chan, Henry H; Alam, Murad; Tannous, Zeina; Anderson, R Rox

    2016-05-01

    Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Budesonide : An Updated Review of its Pharmacological Properties, and Therapeutic Efficacy in Asthma and Rhinitis.

    Science.gov (United States)

    Brogden, Rex N; McTavish, Donna

    1992-09-01

    Inhaled budesonide is now well established in the management of adult and childhood asthma, and when nebulised, shows considerable promise in recurrent wheezing and in severe asthma in infants. Studies conducted since the drug was previously reviewed in the Journal in 1984 have confirmed the comparable efficacy of equal doses of budesonide and beclomethasone dipropionate, the ability of budesonide to reduce oral maintenance corticosteroid requirements, and demonstrated its potential as first-line treatment of mild to moderate asthma. Recent studies have established the usefulness and good tolerability of intranasal budesonide in the treatment of seasonal allergic and perennial rhinitis where the drug is more effective than disodium cromoglycate and at least as effective as beclomethasone dipropionate. After up to 10 years of treatment with inhaled budesonide there is no evidence that the drug damages the tracheobronchial lining or the nasal mucosa. Inhaled corticosteroids continue to play an important role in the treatment of asthma with an increasing focus on their role as first-line therapy, and widespread clinical experience has shown budesonide is an effective and well tolerated member of this class which should be considered where inhaled or intranasal administration of a corticosteroid is indicated. Budesonide has a high ratio of topical to systemic activity compared with reference corticosteroids such as beclomethasone dipropionate. In healthy volunteers, high doses of budesonide cause less depression of plasma cortisol urinary free cortisol excretion than equal dosages of beclomethasone dipropionate. The dosage of inhaled budesonide required to suppress fasting plasma cortisol levels in adults varies considerably between individuals. The adrenal suppressive effect of high dosages of inhaled corticosteroids may be reduced by mouth rinsing and use of a large volume spacer device which reduces oropharyngeal deposition and the amount swallowed. Several studies

  6. Guided Imagery as an Effective Therapeutic Technique: A Brief Review of Its History and Efficacy Research

    Science.gov (United States)

    Utay, Joe; Miller, Megan

    2006-01-01

    Guided imagery is a flexible intervention whose efficacy has been indicated through a large body of research over many decades in counseling and allied fields. It has earned the right to be considered a research-based approach to helping. This article provides a brief introduction to the history of guided imagery and examples of selected research…

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

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

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

  8. Mouse Models for Efficacy Testing of Agents against Radiation Carcinogenesis — A Literature Review

    Directory of Open Access Journals (Sweden)

    Leena Rivina

    2012-12-01

    Full Text Available As the number of cancer survivors treated with radiation as a part of their therapy regimen is constantly increasing, so is concern about radiation-induced cancers. This increases the need for therapeutic and mitigating agents against secondary neoplasias. Development and efficacy testing of these agents requires not only extensive in vitro assessment, but also a set of reliable animal models of radiation-induced carcinogenesis. The laboratory mouse (Mus musculus remains one of the best animal model systems for cancer research due to its molecular and physiological similarities to man, small size, ease of breeding in captivity and a fully sequenced genome. This work reviews relevant M. musculus inbred and F1 hybrid animal models and methodologies of induction of radiation-induced leukemia, thymic lymphoma, breast, and lung cancer in these models. Where available, the associated molecular pathologies are also included.

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

    The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  11. A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer.

    Science.gov (United States)

    Ahn, Richard W; Chen, Feng; Chen, Haimei; Stern, Stephan T; Clogston, Jeffrey D; Patri, Anil K; Raja, Meera R; Swindell, Elden P; Parimi, Vamsi; Cryns, Vincent L; O'Halloran, Thomas V

    2010-07-15

    The clinical success of arsenic trioxide (As(2)O(3)) in hematologic malignancies has not been replicated in solid tumors due to poor pharmacokinetics and dose-limiting toxicity. We have developed a novel nanoparticulate formulation of As(2)O(3) encapsulated in liposomal vesicles or "nanobins" [(NB(Ni,As)] to overcome these hurdles. We postulated that nanobin encapsulation of As(2)O(3) would improve its therapeutic index against clinically aggressive solid tumors, such as triple-negative breast carcinomas. The cytotoxicity of NB(Ni,As), the empty nanobin, and free As(2)O(3) was evaluated against a panel of human breast cancer cell lines. The plasma pharmacokinetics of NB(Ni,As) and free As(2)O(3) were compared in rats to measure drug exposure. In addition, the antitumor activity of these agents was evaluated in an orthotopic model of human triple-negative breast cancer. The NB(Ni,As) agent was much less cytotoxic in vitro than free As(2)O(3) against a panel of human breast cancer cell lines. In contrast, NB(Ni,As) dramatically potentiated the therapeutic efficacy of As(2)O(3) in vivo in an orthotopic model of triple-negative breast cancer. Reduced plasma clearance, enhanced tumor uptake, and induction of tumor cell apoptosis were observed for NB(Ni,As). Nanobin encapsulation of As(2)O(3) improves the pharmacokinetics and antitumor efficacy of this cytotoxic agent in vivo. Our findings demonstrate the therapeutic potential of this nanoscale agent and provide a foundation for future clinical studies in breast cancer and other solid tumors. Copyright 2010 AACR.

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

    Directory of Open Access Journals (Sweden)

    Ying Kong

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

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

    Science.gov (United States)

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

    2006-12-01

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

  14. Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection

    OpenAIRE

    van Niekerk, Gustav; Hattingh, Suzèl M.; Engelbrecht, Anna-Mart

    2016-01-01

    Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cue...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Damal K

    2013-11-01

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

  18. Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis.

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    Søren S Olesen

    Full Text Available BACKGROUND: A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. METHODS: Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area and C5 (control area. To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio. Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. RESULTS: The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3 compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0 (P = 0.001. The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007. The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. CONCLUSIONS: The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and

  19. Quantitative Sensory Testing Predicts Pregabalin Efficacy in Painful Chronic Pancreatitis

    Science.gov (United States)

    Olesen, Søren S.; Graversen, Carina; Bouwense, Stefan A. W.; van Goor, Harry; Wilder-Smith, Oliver H. G.; Drewes, Asbjørn M.

    2013-01-01

    Background A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Methods Sixty-four patients with painful chronic pancreatitis received pregabalin (150–300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. Results The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9–1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5–2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. Conclusions The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient’s individual sensory profile and thus

  20. Efficacy of 3 therapeutic taping configurations for children with brachial plexus birth palsy.

    Science.gov (United States)

    Russo, Stephanie A; Zlotolow, Dan A; Chafetz, Ross S; Rodriguez, Luisa M; Kelly, Devin; Linamen, Holly; Richards, James G; Lubahn, John D; Kozin, Scott H

    2017-04-25

    Cross-sectional clinical measurement study. Scapular winging is a frequent complaint among children with brachial plexus birth palsy (BPBP). Therapeutic taping for scapular stabilization has been reported to decrease scapular winging. This study aimed to determine which therapeutic taping construct was most effective for children with BPBP. Twenty-eight children with BPBP participated in motion capture assessment with 4 taping conditions: (1) no tape, (2) facilitation of rhomboid major and rhomboid minor, (3) facilitation of middle and lower trapezius, and (4) facilitation of rhomboid major, rhomboid minor, and middle and lower trapezius (combination of both 2 and 3, referred to as combined taping). The participants held their arms in 4 positions: (1) neutral with arms by their sides, (2) hand to mouth, (3) hand to belly, and (4) maximum crossbody adduction (CBA). The scapulothoracic, glenohumeral and humerothoracic (HT) joint angles and joint angular displacements were compared using multivariate analyses of variance with Bonferroni corrections. Scapular winging was significantly decreased in both the trapezius and combined taping conditions in all positions compared with no tape. Rhomboids taping had no effect. Combined taping reduced HT CBA in the CBA position. Rhomboid taping cannot be recommended for treatment of children with BPBP. Both trapezius and combined taping approaches reduced scapular winging, but HT CBA was limited with combined taping. Therefore, therapeutic taping of middle and lower trapezius was the most effective configuration for scapular stabilization in children with BPBP. Resting posture improved, but performance of the positions was not significantly improved. Level II. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  1. Sonoporation Increases Therapeutic Efficacy of Inducible and Constitutive BMP2/7 In Vivo Gene Delivery

    Science.gov (United States)

    Hofmann, Anna T.; Slezak, Paul; Schuetzenberger, Sebastian; Kaipel, Martin; Schwartz, Ernst; Neef, Anne; Nomikou, Nikolitsa; Nau, Thomas; van Griensven, Martijn; McHale, Anthony P.; Redl, Heinz

    2014-01-01

    Abstract An ideal novel treatment for bone defects should provide regeneration without autologous or allogenous grafting, exogenous cells, growth factors, or biomaterials while ensuring spatial and temporal control as well as safety. Therefore, a novel osteoinductive nonviral in vivo gene therapy approach using sonoporation was investigated in ectopic and orthotopic models. Constitutive or regulated, doxycycline-inducible, bone morphogenetic protein 2 and 7 coexpression plasmids were repeatedly applied for 5 days. Ectopic and orthotopic gene transfer efficacy was monitored by coapplication of a luciferase plasmid and bioluminescence imaging. Orthotopic plasmid DNA distribution was investigated using a novel plasmid-labeling method. Luciferase imaging demonstrated an increased trend (61% vs. 100%) of gene transfer efficacy, and micro-computed tomography evaluation showed significantly enhanced frequency of ectopic bone formation for sonoporation compared with passive gene delivery (46% vs. 100%) dependent on applied ultrasound power. Bone formation by the inducible system (83%) was stringently controlled by doxycycline in vivo, and no ectopic bone formation was observed without induction or with passive gene transfer without sonoporation. Orthotopic evaluation in a rat femur segmental defect model demonstrated an increased trend of gene transfer efficacy using sonoporation. Investigation of DNA distribution demonstrated extensive binding of plasmid DNA to bone tissue. Sonoporated animals displayed a potentially increased union rate (33%) without extensive callus formation or heterotopic ossification. We conclude that sonoporation of BMP2/7 coexpression plasmids is a feasible, minimally invasive method for osteoinduction and that improvement of bone regeneration by sonoporative gene delivery is superior to passive gene delivery. PMID:24164605

  2. Therapeutic antitumor efficacy of monoclonal antibody against Claudin-4 for pancreatic and ovarian cancers.

    Science.gov (United States)

    Suzuki, Masayo; Kato-Nakano, Mariko; Kawamoto, Shinobu; Furuya, Akiko; Abe, Yuzuru; Misaka, Hirofumi; Kimoto, Naoya; Nakamura, Kazuyasu; Ohta, So; Ando, Hiroshi

    2009-09-01

    Claudin-4 (CLDN4) is a tetraspanin transmembrane protein of tight junction structure and is highly expressed in pancreatic and ovarian cancers. In this study, we aimed to generate an anti-Claudin-4 monoclonal antibody (mAb) and evaluate its antitumor efficacy in vitro and in vivo. To isolate specific mAb, we generated CLDN3, 4, 5, 6, and 9, expressing Chinese hamster ovary (CHO) cells, and then used them as positive and negative targets through cell-based screening. As a result, we succeeded in isolating KM3900 (IgG2a), which specifically bound to CLDN4, from BXSB mice immunized with pancreatic cancer cells. Immunoprecipitation and flow cytometry analysis revealed that KM3900 recognized the conformational structure and bound to extracellular loop 2 of CLDN4. Furthermore, binding of KM3900 was detected on CLDN4-expressing pancreatic and ovarian cancer cells, but not on negative cells. Next, we made the mouse-human chimeric IgG1 (KM3934) and evaluated its antitumor efficacy. KM3934 induced dose-dependent antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro, and significantly inhibited tumor growth in MCAS or CFPAC-1 xenograft SCID mice in vivo (P < 0.05). These results suggest that mAb therapy against CLDN4 is promising for pancreatic and ovarian cancers.

  3. Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized therapeutic vaccine of Parietaria judaica.

    Science.gov (United States)

    García-Sellés, J; Pascual, A; Funes, E; Pagán, J A; López, J-D; Negro, J M; Hernández, J

    2003-01-01

    The inhalation of Parietaria judaica pollen is a common cause of allergic respiratory diseases in the Mediterranean area. The objective of this study was to investigate the safety and clinical efficacy of a chemically modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria judaica. Thirty patients with a well-documented clinical history of seasonal rhinitis and clinical sensitivity to Parietaria judaica pollen were included in a randomized trial during 12 months. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into 2 groups of 15 individuals; group A received the modified extract and group C did not receive specific immunotherapy. Any adverse event was recorded to assess safety. Symptom scores, symptomatic medication use and the results of specific nasal challenges (before and after 12 months of treatment) were recorded to evaluate clinical efficacy. The treatment schedule consisted of an incremental phase of 5 injections and a maintenance dosage of 0.5 ml per month. Each patient received 14 injections during this period. All the patients completed the trial and no adverse reactions related to immunotherapy were recorded. A significant difference (p Parietaria judaica pollen is safe and effective to treat patients with allergic rhinitis and clinical sensitivity to this pollen.

  4. Adaptive clinical trial designs for simultaneous testing of matched diagnostics and therapeutics.

    Science.gov (United States)

    Scher, Howard I; Nasso, Shelley Fuld; Rubin, Eric H; Simon, Richard

    2011-11-01

    A critical challenge in the development of new molecularly targeted anticancer drugs is the identification of predictive biomarkers and the concurrent development of diagnostics for these biomarkers. Developing matched diagnostics and therapeutics will require new clinical trial designs and methods of data analysis. The use of adaptive design in phase III trials may offer new opportunities for matched diagnosis and treatment because the size of the trial can allow for subpopulation analysis. We present an adaptive phase III trial design that can identify a suitable target population during the early course of the trial, enabling the efficacy of an experimental therapeutic to be evaluated within the target population as a later part of the same trial. The use of such an adaptive approach to clinical trial design has the potential to greatly improve the field of oncology and facilitate the development of personalized medicine. ©2011 AACR

  5. EGCG/gelatin-doxorubicin gold nanoparticles enhance therapeutic efficacy of doxorubicin for prostate cancer treatment.

    Science.gov (United States)

    Tsai, Li-Chu; Hsieh, Hao-Ying; Lu, Kun-Ying; Wang, Sin-Yu; Mi, Fwu-Long

    2016-01-01

    Development of epigallocatechin gallate (EGCG) and gelatin-doxorubicin conjugate (GLT-DOX)-coated gold nanoparticles (DOX-GLT/EGCG AuNPs) for fluorescence imaging and inhibition of prostate cancer cell growth. AuNPs alternatively coated with EGCG and DOX-GLT conjugates were prepared by a layer-by-layer assembly method. The physicochemical properties of the AuNPs and the effect of Laminin 67R receptor-mediated endocytosis on the anticancer efficacy of the AuNPs were examined. The AuNPs significantly inhibit the proliferation of PC-3 cancer cell and the enzyme-responsive intracellular release of DOX could be tracked by monitoring the recovery of the fluorescence signal of DOX. Laminin 67R receptor-mediated delivery of DOX using the AuNPs enhanced cellular uptake of DOX and improved apoptosis of PC-3 cells.

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

    Directory of Open Access Journals (Sweden)

    S S Agarwal

    2015-01-01

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

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

    Science.gov (United States)

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

    2018-01-08

    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 T2-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 (Fe3O4@PEG) exhibited high r2 of 571 mM-1 s-1 and saturation magnetization (Ms) 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 enhanced by Fe3O4@PEG (d = 32 nm) could be used to predict the therapeutic efficacy of the micelle drugs (d ≤ 32 nm) in a certain period of time. Fe3O4@PEG has a potential to serve as an ideal MRI contrast agent to visualize the EPR effect in patients for accurate medication guidance of micelle drugs in the future treatment of tumors.

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

    Science.gov (United States)

    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).

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

    Directory of Open Access Journals (Sweden)

    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.

  10. The therapeutic efficacy of somatic acupuncture is not increased by auriculotherapy: a randomised, blind control study in cervical myofascial pain.

    Science.gov (United States)

    Ceccherelli, Francesco; Tortora, Paola; Nassimbeni, Cecilia; Casale, Roberto; Gagliardi, Giuseppe; Giron, Giampiero

    2006-03-01

    Auriculotherapy (ear acupuncture) is a therapeutic technique in which points on the auricle are stimulated with needles. Usually it is combined with somatic acupuncture because of possible synergy, although the efficacy of this pairing has neither been confirmed nor disproved. The aim of this study was to verify: (1) if somatic acupuncture can reduce myofascial cervical pain; (2) if concomitant auriculotherapy improves the efficacy of somatic acupuncture. A group of 62 patients affected by cervical myofascial pain was randomly divided into two groups of 31. Group A (6 males and 25 females) underwent eight sessions of somatic acupuncture. Group B (7 males and 24 females) underwent eight sessions of somatic acupuncture in the same way as group A, paired with auriculotherapy. Pain was scored using the McGill Pain Questionnaire before and at the end of treatment, and 1 and 3 months later. The results showed that both somatic acupuncture and somatic plus ear acupuncture have a positive effect in reducing pain. The pain intensity score was 40.70 +/- 17.78 in group A before therapy and 13.32 +/- 9.62 after therapy; in group B it was 38.90 +/- 15.31 and 13.43 +/- 10.96. Somatic plus auriculotherapy was therefore not statistically significantly superior to somatic therapy alone in the treatment of cervical myofascial pain.

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

    Science.gov (United States)

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

    2013-11-01

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

  12. Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation.

    Science.gov (United States)

    Morelli, Silvia; Reboldi, Gianpaolo; Moretti, Sonia; Menicali, Elisa; Avenia, Nicola; Puxeddu, Efisio

    2016-06-01

    Oral levothyroxine (L-T4) is the mainstay of hypothyroidism treatment. Many factors may influence its absorption, including the timing of administration. Objective of the study is to demonstrate the therapeutic equivalence of administering liquid L-T4 with breakfast or 10 min before breakfast. This was a pilot study conducted with a crossover design AB/BA where A stays for L-T4 with breakfast and B for L-T4 10 min before breakfast. A post hoc analysis was conducted to compare L-T4 administered at breakfast or 10 min before breakfast with L-T4 administered 30 min before breakfast. Sixty-one hypothyroid patients were enrolled and assigned to one of the two treatment sequences. All patients were evaluated for TSH levels at the end of each period. Fifty-nine patients completed the study. The mean thyrotropin concentration was 1.52 ± 0.73 µU/ml when L-T4 was administered with breakfast and 1.46 ± 0.81 µU/ml when it was taken 10 min before breakfast, without clinically and statistically significant differences (P = 0.59), regardless of treatment sequence and period. The mean thyrotropin concentration was 1.54 ± 0.9 µU/ml when L-T4 was administered at 0-10 min intervals before breakfast and 1.25 ± 0.7 µU/ml when it was taken 30 min before breakfast (ratio = 1.23, within our definition of equivalence set at 0.8-1.25). There is therapeutic equivalence between liquid L-T4 administration at breakfast or 10 min before breakfast. We can also hypothesize that there are no clinically relevant differences between liquid L-T4 administration 30 min before breakfast or at shorter intervals.

  13. Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia?

    Directory of Open Access Journals (Sweden)

    Argirović Aleksandar

    2013-01-01

    Full Text Available Background/Aim. It has been observed that a large number of patients with low urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH has been treated with a combination of tamsulosin (TAM + Serenoa repens (SR (TAM + SR. The aim of this study was to compare a combination TAM + SR with TAM and SR alone, to see if there was any difference in efficacy and tolerance of each in patients with LUTS/BPH. Methods. In this prospective study patients had to have prostate volume (PV 3, a maximal flow rate (Qmax of 5-15 mL/s, with post voiding residual volume (PVR < 150 mL and serum prostatic antigen (PSA < 4 ng/mL. TAM (0.4 mg was administered once a day, SR (320 mg daily or SR (320 mg + TAM (0.4 mg daily for a median period of 6 months. Results. A total of 297 patients were recruited, whereas 265 patients were fully available: 87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There was no statistically significant difference between the treatment groups in the sense of demographic and other baseline parameters. No difference was found among the 3 treatment groups, neither in the major endpoint of the study in the sense of a change between baseline and final evaluation in total IPSS, obstructive and irritative subscores, improvement of QoLs, increase in Qmax, nor for the second endpoint including diminution of PV, PSA and PVR. During the treatment period 20 (23% of the patients managed with TAM and 17 (21% with TAM + SR had drug-treated with related adverse reactions. No adverse effect was detected in the group SR. Conclusion. Treatment of BPH by both SR and TAM seems to be efficacious alone. None of them had superiority over another and, additionally, a combined therapy (TAM + SR does not provide extra benefits. Furthermore, SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

  14. Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia?

    Science.gov (United States)

    Argirović, Aleksandar; Argirović, Djordje

    2013-12-01

    It has been observed that a large number of patients with low urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH)) has been treated with a combination of tamsulosin (TAM) + Serenoa repens (SR) (TAM + SR). The aim of this study was to compare a combination TAM + SR with TAM and SR alone, to see if there was any difference in efficacy and tolerance of each in patients with LUTS/BPH. In this prospective study patients had to have prostate volume (PV) 3, a maximal flow rate (Qmax) of 5-15 mL/s, with post voiding residual volume (PVR) < 150 mL and serum prostatic antigen (PSA) < 4 ng/mL. TAM (0.4 mg) was administered once a day, SR (320 mg) daily or SR (320 mg) + TAM (0.4 mg) daily for a median period of 6 months. A total of 297 patients were recruited, whereas 265 patients were fully available: 87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There was no statistically significant difference between the treatment groups in the sense of demographic and other baseline parameters. No difference was found among the 3 treatment groups, neither in the major endpoint of the study in the sense of a change between baseline and final evaluation in total IPSS, obstructive and irritative subscores, improvement of QoLs, increase in Qmax, nor for the second endpoint including diminution of PV, PSA and PVR. During the treatment period 20 (23%) of the patients managed with TAM and 17 (21%) with TAM + SR had drug- treated with related adverse reactions. No adverse effect was detected in the group SR. Treatment of BPH by both SR and TAM seems to be efficacious alone. None of them had superiority over another and, additionally, a combined therapy (TAM + SR) does not provide extra benefits. Furthermore, SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

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

    Science.gov (United States)

    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

    2013-06-01

    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 hypertension-induced heart disease. In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression. Circulating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.

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

    Science.gov (United States)

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

    2017-01-01

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

  17. An artificial niche preserves the quiescence of muscle stem cells and enhances their therapeutic efficacy.

    Science.gov (United States)

    Quarta, Marco; Brett, Jamie O; DiMarco, Rebecca; De Morree, Antoine; Boutet, Stephane C; Chacon, Robert; Gibbons, Michael C; Garcia, Victor A; Su, James; Shrager, Joseph B; Heilshorn, Sarah; Rando, Thomas A

    2016-07-01

    A promising therapeutic strategy for diverse genetic disorders involves transplantation of autologous stem cells that have been genetically corrected ex vivo. A major challenge in such approaches is a loss of stem cell potency during culture. Here we describe an artificial niche for maintaining muscle stem cells (MuSCs) in vitro in a potent, quiescent state. Using a machine learning method, we identified a molecular signature of quiescence and used it to screen for factors that could maintain mouse MuSC quiescence, thus defining a quiescence medium (QM). We also engineered muscle fibers that mimic the native myofiber of the MuSC niche. Mouse MuSCs maintained in QM on engineered fibers showed enhanced potential for engraftment, tissue regeneration and self-renewal after transplantation in mice. An artificial niche adapted to human cells similarly extended the quiescence of human MuSCs in vitro and enhanced their potency in vivo. Our approach for maintaining quiescence may be applicable to stem cells isolated from other tissues.

  18. Patient-recorded outcome to assess therapeutic efficacy in protoporphyria-induced dermal phototoxicity: a proposal

    Directory of Open Access Journals (Sweden)

    Minder Christoph E

    2010-06-01

    Full Text Available Abstract Background Protoporphyria (PP resulting from two rare, inherited diseases of heme biosynthesis leads to dermal phototoxicity by accumulation of the heme precursor protoporphyrin IX. No standardized tools to quantify the degree of PP-related phototoxicity and its change by medical intervention have been published. Methods Results from a questionnaire completed by 17 affected individuals were used to determine the relative importance of two main components of PP-related phototoxicity, skin pain and sunlight exposure time, with respect to the effectiveness of any particular medical treatment. Results Inter-rater reliability was 0.71 (n = 490, repeated estimates by four identical individuals showed high reproducibility (Slope = 1, intercept = 0, n = 136, Passing-Bablock. Six different models were developed, three of them showed good correlation with effectiveness estimates. Data from an unpublished trial indicated that the model with highest potential of responsiveness was the so called "Exposure times [multiplied by] Freedom from Pain" (ETFP. The minimal clinically important difference (MID was 15 (10.2-20.4 ETFP scores, representing 28% of the standard deviation of the clinical trial data and 2.9% of its total range. Conclusions Among the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP. The results of this study have provided sufficient validation of the ETFP model that is likely to prove useful in future clinical trials.

  19. Patient-recorded outcome to assess therapeutic efficacy in protoporphyria-induced dermal phototoxicity: a proposal.

    Science.gov (United States)

    Minder, Elisabeth I; Schneider-Yin, Xiaoye; Minder, Christoph E

    2010-06-21

    Protoporphyria (PP) resulting from two rare, inherited diseases of heme biosynthesis leads to dermal phototoxicity by accumulation of the heme precursor protoporphyrin IX. No standardized tools to quantify the degree of PP-related phototoxicity and its change by medical intervention have been published. Results from a questionnaire completed by 17 affected individuals were used to determine the relative importance of two main components of PP-related phototoxicity, skin pain and sunlight exposure time, with respect to the effectiveness of any particular medical treatment. Inter-rater reliability was 0.71 (n = 490), repeated estimates by four identical individuals showed high reproducibility (Slope = 1, intercept = 0, n = 136, Passing-Bablock).Six different models were developed, three of them showed good correlation with effectiveness estimates. Data from an unpublished trial indicated that the model with highest potential of responsiveness was the so called "Exposure times [multiplied by] Freedom from Pain" (ETFP). The minimal clinically important difference (MID) was 15 (10.2-20.4) ETFP scores, representing 28% of the standard deviation of the clinical trial data and 2.9% of its total range. Among the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP. The results of this study have provided sufficient validation of the ETFP model that is likely to prove useful in future clinical trials.

  20. Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei.

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    Saja Asakrah

    Full Text Available Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2 production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2 expression and decreased nitric oxide (NO production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens.

  1. Efficacy of therapeutic ultrasound in the treatment of spasticity: a randomized controlled study.

    Science.gov (United States)

    Sahin, Nilay; Ugurlu, Hatice; Karahan, Ali Yavuz

    2011-01-01

    The purpose of this study was to investigate the effect of ultrasound (US) on the spasticity occurring in the ankle plantar flexor muscles after a cerebrovascular event. According to the modified Ashworth scale (MAS), the hemiplegic patients with stage 2-3 spasticity on the ankle plantar flexor muscles were enrolled in the study and divided into two groups. Passive stretching exercise was applied to both groups. Additionally, 10-minute US was applied to one of the groups, using the mode of continuous wave of 1.5w/cm^{2} to the calf muscles before stretching. In order to monitor the efficacy of the treatment in the patients, MAS, Hmax/Mmax ratio, the ankle range of motion (ROM), Functional Independence Measure and Brunnstrom Motor Recovery Stage were evaluated. While a significant recovery was monitored in the MAS and ankle ROM measurements after treatment in both groups, no change was obtained in the other parameters. No significant difference was detected in any of the measurements between the groups. In this study, US treatment applied in combination with the ankle plantar flexor muscles passive stretching exercise was determined to have no effect on the stretching treatment in minimizing the spasticity.

  2. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

    Science.gov (United States)

    Nam, Eon Jeong; Kang, Jin Hee; Sa, Keum Hee; Sung, Shijin; Park, Jae Yong; Jo, Dong-Gyu; Park, Jae Hyung; Kim, In San; Kang, Young Mo

    2016-01-01

    Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis. We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA) model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages. MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo. The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for chronic

  3. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

    Directory of Open Access Journals (Sweden)

    Eon Jeong Nam

    Full Text Available Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3, which consists of four fas-1 domains and an Arg-Gly-Asp (RGD motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA. The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis.We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00 and MMP-2-cleavable peptide complex (MFK902. MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages.MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg. MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo.The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for

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

    Science.gov (United States)

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

    2014-06-01

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

  5. Fish oils against Burkholderia and Pseudomonas aeruginosa: in vitro efficacy and their therapeutic and prophylactic effects on infected Galleria mellonella larvae.

    Science.gov (United States)

    Mil-Homens, D; Ferreira-Dias, S; Fialho, A M

    2016-06-01

    This study investigates the antimicrobial effects of fish oil-based formulas rich in omega-3 fatty acids (free fatty acids, ethyl esters or triacylglycerols), against cystic fibrosis (CF) pathogens (Burkholderia cenocepacia K56-2 and Pseudomonas aeruginosa PAO1), often resistant to multiple antibiotics. The fish oils have shown antibacterial efficacy, although activity was highest for the one containing the fatty acid EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in their free form (MIC value is 1·87% v/v for both pathogens). To test whether the fish oils could have a therapeutic and prophylactic potential in vivo, we assessed its efficacy using a Galleria mellonella caterpillar model of infection. The treatment of infected larvae with a single dose (7 h post infection) enhances the survival of larvae, being more pronounced with the free fatty acid form (EPAX 6000 FA). Moreover, we observed that the prophylactic food provision of the fish oil EPAX 6000 FA during 12 days prior to bacterial infection extended the life of the infected larvae. The fish oils, particularly in the free fatty acid form, are active in killing Burkholderia and Ps. aeruginosa. The possibility of using fish oils for the treatment of bacterial infections in CF patients. © 2016 The Society for Applied Microbiology.

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

    Directory of Open Access Journals (Sweden)

    Nande R

    2015-11-01

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

  7. Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension.

    Science.gov (United States)

    Hadri, Lahouaria; Kratlian, Razmig G; Benard, Ludovic; Maron, Bradley A; Dorfmüller, Peter; Ladage, Dennis; Guignabert, Christophe; Ishikawa, Kiyotake; Aguero, Jaume; Ibanez, Borja; Turnbull, Irene C; Kohlbrenner, Erik; Liang, Lifan; Zsebo, Krisztina; Humbert, Marc; Hulot, Jean-Sébastien; Kawase, Yoshiaki; Hajjar, Roger J; Leopold, Jane A

    2013-07-30

    Pulmonary arterial hypertension (PAH) is characterized by dysregulated proliferation of pulmonary artery smooth muscle cells leading to (mal)adaptive vascular remodeling. In the systemic circulation, vascular injury is associated with downregulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) and alterations in Ca(2+) homeostasis in vascular smooth muscle cells that stimulate proliferation. We, therefore, hypothesized that downregulation of SERCA2a is permissive for pulmonary vascular remodeling and the development of PAH. SERCA2a expression was decreased significantly in remodeled pulmonary arteries from patients with PAH and the rat monocrotaline model of PAH in comparison with controls. In human pulmonary artery smooth muscle cells in vitro, SERCA2a overexpression by gene transfer decreased proliferation and migration significantly by inhibiting NFAT/STAT3. Overexpresion of SERCA2a in human pulmonary artery endothelial cells in vitro increased endothelial nitric oxide synthase expression and activation. In monocrotaline rats with established PAH, gene transfer of SERCA2a via intratracheal delivery of aerosolized adeno-associated virus serotype 1 (AAV1) carrying the human SERCA2a gene (AAV1.SERCA2a) decreased pulmonary artery pressure, vascular remodeling, right ventricular hypertrophy, and fibrosis in comparison with monocrotaline-PAH rats treated with a control AAV1 carrying β-galactosidase or saline. In a prevention protocol, aerosolized AAV1.SERCA2a delivered at the time of monocrotaline administration limited adverse hemodynamic profiles and indices of pulmonary and cardiac remodeling in comparison with rats administered AAV1 carrying β-galactosidase or saline. Downregulation of SERCA2a plays a critical role in modulating the vascular and right ventricular pathophenotype associated with PAH. Selective pulmonary SERCA2a gene transfer may offer benefit as a therapeutic intervention in PAH.

  8. Enhanced therapeutic efficacy of LHRHa-targeted brucea javanica oil liposomes for ovarian cancer.

    Science.gov (United States)

    Ye, Hongxia; Liu, Xiaojuan; Sun, Jiangchuan; Zhu, Shenyin; Zhu, Yi; Chang, Shufang

    2016-10-29

    Although brucea javanica oil liposomes (BJOLs) have been used clinically to treat ovarian cancer, its clinical efficacy is often limited by systemic side effects due to non-specific distribution. Luteinizing hormone releasing hormone receptor (LHRHR) is overexpressed in most ovarian cancers but negligibly expressed in most of the other visceral organs. In this study, we aimed to develop a novel LHRHa targeted and BJO-loaded liposomes (LHRHa-BJOLs), and investigate its characteristics, targeting ability and anti-ovarian cancer efficiency both in vitro and in vivo. The LHRHa-BJOLs were prepared by film-dispersion and biotin-streptavidin linkage methods, and characterized in terms of its morphology, particle size, zeta potential, ligand conjugation, encapsulation efficiency and stability. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured human ovarian cancer A2780/DDP cells, and in vivo using ovarian cancer-bearing nude mice. The LHRHa-BJOLs were successfully synthesized, with a uniformly spherical shape, appropriate particle size and zeta potential, as well as a high encapsulation efficiency. Compared to non-targeted liposomes and BJO emulsion, the LHRHa-BJOLs could significantly increase specific intracellular uptaking rate, enhance cell inhibitory effect and induce cell apoptosis in A2780/DDP cells in vitro. Meanwhile, LHRHa-BJOLs also had a significantly stronger activity of targeting tumor tissue, inhibiting tumor growth, inducing tumor apoptosis and prolonging survival time in ovarian cancer-bearing mice in vivo. Our experiment suggests that LHRHa-BJOLs may be a useful targeted drug for the treatment of ovarian cancer.

  9. Therapeutic efficacy of bromelain in impacted third molar surgery: a randomized controlled clinical study.

    Science.gov (United States)

    Ordesi, Paolo; Pisoni, Luca; Nannei, Pierluigi; Macchi, Maurizia; Borloni, Roberto; Siervo, Sandro

    2014-09-01

    Bromelain is the name given to a family of proteolytic enzymes obtained from Ananas comosus, the pineapple plant. It is considered a potent anti-inflammatory and antiedematous substance. Surgery of impacted third molars in the outpatient setting is one of the procedures most often associated with postoperative pain and swelling. The aim of this study was to evaluate the efficacy of bromelain in reducing postoperative pain and swelling. 80 patients were recruited to the study from patients attending the Maxillofacial Surgery Unit of the Istituto Stomatologico Italiano, Milan, Italy, for impacted third molar surgery. At time 0 when surgery was performed, patients started simultaneous antibiotic and analgesic therapy. On the following day, patients were divided into two groups. Patients in group 1 were prescribed bromelain. Patients in group 2 were prescribed only the analgesic if required. Three parameters were evaluated: pain, edema, and erythema. The first evaluation visit was performed 3 hours after surgery, the second 48 hours after surgery, and the final evaluation 7 days after surgery. Postoperative pain, edema, and erythema were significantly lower in the study group than in the control group. Analgesic consumption, both in terms of days of treatment and number of tablets taken, was slightly lower in the study group. Only one adverse event was recorded, which occurred in a patient in the control group. The present study demonstrates an important anti-inflammatory and anti-edematous effect of bromelain. Statistical analysis shows that in the group treated with bromelain the inflammatory response was significantly less than in the control group.

  10. The cardioprotector dexrazoxane augments therapeutic efficacy of mitoxantrone in experimental autoimmune encephalomyelitis

    Science.gov (United States)

    WEILBACH, F X; CHAN, A; TOYKA, K V; GOLD, R

    2004-01-01

    The present study investigates the immunological effects of a combination treatment of mitoxantrone and the cardioprotector dexrazoxane in experimental autoimmune encephalomyelitis (EAE). Mitoxantrone, an anthracycline-derived immunosuppressive drug has been approved recently for treatment of very active multiple sclerosis (MS). Its prolonged use is limited due to its cardiotoxic properties. Dexrazoxane (DZR (S)-(+)-1,2-bis (3,5.dioxopiperazinyl)propane, ICRF-187) is an iron III chelator which in animal models and in cancer patients reduces anthracycline and mitoxantrone induced cardiotoxicity when given immediately before these agents. We examined the immunological effects of dexrazoxane in combination with mitoxantrone in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. EAE was induced by active immunization with myelin basic protein (MBP) or by adoptive transfer of MBP specific T cells (AT-EAE). The clinical course, spinal cord pathology, activity of metalloproteinases (MMP-2 and MMP-9) and T cell apoptosis were assessed. Monotherapy with DZR ameliorated slightly the course of actively induced EAE and AT-EAE. The combination of DZR and mitoxantrone was superior to mitoxantrone given alone. Clinical amelioration ran in parallel with the marked reduction of inflammatory infiltration which was nearly abolished by the combination treatment. DZR did not affect the activity of metalloproteinase 9 and did not increase the proportion of apoptotic lymph node cells ex vivo or T cells in situ. We conclude that in addition to its cardioprotective role, DZR augments mitoxantrone-mediated immunosuppressive effects in animal models of human central nervous system (CNS) autoimmune disease. Clinical trials in MS patients are warranted to evaluate the unexpected immunosuppressive efficacy of DZR as add-on treatment. PMID:14678264

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

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

    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. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group

  14. Assessing the safety and efficacy of drugs used in preparing the nose for diagnostic and therapeutic procedures: a systematic review.

    Science.gov (United States)

    Saif, A M; Farboud, A; Delfosse, E; Pope, L; Adke, M

    2016-10-01

    Local anaesthetics and vasoconstrictors are essential for pain control and to aid intra-operative haemostasis in nasal procedures. They also improve access, and reduce discomfort when performing nasal endoscopy. There are no clear guidelines on preparing the nose despite evermore diagnostic and therapeutic procedures utilising the nose as a point of access. This review aims to identify nasal preparations used in diagnostic and therapeutic nasal procedures and to examine their safety and efficacy. Systematic review. A search was carried out using PubMed, MEDLINE, Ovid EMBASE, the Cochrane library and references from the included articles. The inclusion criteria included: full-text English language articles with regard to nasal preparation for surgery. Case reports, systematic reviews, meta-analysis, double-blind placebo controlled randomised trials (RCTs) and case series were included. A total of 53 articles were retrieved: 13 articles on nasal preparation for operative procedures, six on functional endoscopic sinus surgery and 22 on nasendoscopy as well as six case reports. Cocaine was the most widely used topical preparation for operative procedures but was associated with more side-effects; thus, topical tetracaine and levobupivacaine infiltration are alternatives with equivalent efficacy but reduced adverse effects. All articles reviewed for functional endoscopic sinus surgery used a mixture containing lidocaine, adrenaline or both. Flexible nasendoscopy causes minimal patient discomfort and preparation is only recommended in selected patients, in contrast to rigid nasendoscopy which requires preparation. For operative procedures, such as septorhinoplasty, a single agent tetracaine or levobupivicaine provides an improved surgical field. In functional endoscopic sinus surgery, lidocaine-adrenaline preparations have resulted in significantly better surgical and patient outcomes. There is little evidence to support the routine use of pre-procedural nasal

  15. Self-Assembling Monomeric Nucleoside Molecular Nanoparticles Loaded with 5-FU Enhancing Therapeutic Efficacy against Oral Cancer.

    Science.gov (United States)

    Zhao, Hang; Feng, Hui; Liu, Dongjuan; Liu, Jiang; Ji, Ning; Chen, Fangman; Luo, Xiaobo; Zhou, Yu; Dan, Hongxia; Zeng, Xin; Li, Jing; Sun, Congkui; Meng, Jinyu; Ju, Xiaojie; Zhou, Min; Yang, Hanshuo; Li, Longjiang; Liang, Xinhua; Chu, Liangyin; Jiang, Lu; He, Yang; Chen, Qianming

    2015-10-27

    Conventional oligonucleotide based drug delivery systems suffer from lengthy synthetic protocols, high cost, and poor chemical or enzymatic stability under certain circumstances. Canonical free individual nucleosides cannot form stable nanostructures in aqueous solution as drug vehicles. Here, we report the development of a monomeric self-assembled nucleoside nanoparticle (SNNP) into an efficient drug delivery system which has currently no parallel in such field. This was achieved using a l-configurational pyrimido[4,5-d]pyrimidine nucleoside building block that can form robust discrete nanoparticles in just one step with water as the sole solvent. Its high biocompatibility and low toxicity was demonstrated in vitro and in vivo. In mouse xenograft model of oral squamous cell carcinoma (OSCC), SNNP loaded with 5-fluoro-uracile (5-FU-SNNP) remarkably retarded the tumor growth compared with free 5-FU, albeit SNNP alone showed no antitumor effect. The stability in blood circulation and the effective concentration of 5-FU in tumor tissue were increased upon the loading with SNNP. TUNEL and immunohistochemistry analyses further indicated that the superior in vivo antitumor efficacy of 5-FU-SNNP compared to free 5-FU was associated with an enhanced degree of inhibition of cell proliferation and stimulation of cell apoptosis. Furthermore, SNNP alleviated the toxic side effects of 5-FU. These findings suggested that when loaded with SNNP, 5-FU has better antitumor efficacy and lower side effects, indicating that SNNP can efficiently act as a readily accessible, robust, biocompatible and low-toxic nanobiomaterial which may find wide therapeutic applications clinically in the future.

  16. Therapeutic efficacy of macrolides, minocycline, and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae pneumonia in pediatric patients.

    Science.gov (United States)

    Kawai, Yasuhiro; Miyashita, Naoyuki; Kubo, Mika; Akaike, Hiroto; Kato, Atsushi; Nishizawa, Yoko; Saito, Aki; Kondo, Eisuke; Teranishi, Hideto; Ogita, Satoko; Tanaka, Takaaki; Kawasaki, Kozo; Nakano, Takashi; Terada, Kihei; Ouchi, Kazunobu

    2013-05-01

    The importance of macrolide-resistant (MR) Mycoplasma pneumoniae has become much more apparent in the past decade. We investigated differences in the therapeutic efficacies of macrolides, minocycline, and tosufloxacin against MR M. pneumoniae. A total of 188 children with M. pneumoniae pneumonia confirmed by culture and PCR were analyzed. Of these, 150 patients had a strain with an MR gene and 134 had one with an A-to-G mutation at position 2063 of M. pneumoniae 23S rRNA domain V. Azithromycin (n = 27), clarithromycin (n = 23), tosufloxacin (n = 62), or minocycline (n = 38) was used for definitive treatment of patients with MR M. pneumoniae. Defervescence within 48 h after the initiation of antibiotic therapy was observed in 41% of the patients in the azithromycin group, 48% of those in the clarithromycin group, 69% of those in the tosufloxacin group, and 87% of those in the minocycline group. The average number of days of fever after the administration of antibiotic treatment was lower in the minocycline and tosufloxacin groups than in the macrolide groups. The decrease in the M. pneumoniae burden, as estimated by the number of DNA copies, after 48 to 96 h of treatment was more rapid in patients receiving minocycline (P = 0.016) than in those receiving tosufloxacin (P = 0.049), azithromycin (P = 0.273), or clarithromycin (P = 0.107). We found that the clinical and bacteriological efficacies of macrolides against MR M. pneumoniae pneumonia was low. Our results indicated that minocycline rather than tosufloxacin can be considered the first-choice drug for the treatment of M. pneumoniae pneumonia in children aged ≥ 8 years.

  17. ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy.

    Science.gov (United States)

    Monga, Isha; Qureshi, Abid; Thakur, Nishant; Gupta, Amit Kumar; Kumar, Manoj

    2017-09-07

    Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb , (ii) ASPsiPred , and (iii) analysis tools like ASP-siOffTar ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully complementary mutant (Eff mut ) and wild-type allele (Eff wild ) with one mismatch by ASPsiPred SVM and ASPsiPred matrix , respectively. In ASPsiPred SVM , 922 unique ASP-siRNAs with experimentally validated quantitative Eff mut were used. During 10-fold cross-validation (10nCV) employing various sequence features on the training/testing dataset (T737), the best predictive model achieved a maximum Pearson's correlation coefficient (PCC) of 0.71. Further, the accuracy of the classifier to predict Eff mut against novel genes was assessed by leave one target out cross-validation approach (LOTOCV). ASPsiPred matrix was constructed from rule-based studies describing the effect of single siRNA:mRNA mismatches on the efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first database, prediction algorithm, and off-target analysis tool that is expected to accelerate research in the field of RNAi

  18. [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in patients with exacerbated chronic bronchitis].

    Science.gov (United States)

    Scillieri, E

    1990-01-01

    4-carbomethoxythiazolidine HCl has been administered to 24 patients (aged between 64 and 86) suffering from new acute stages of chronic bronchitis. The patients have been submitted to a double-blind test and have been subdivided into four groups; each of them was administered a placebo or the a.m. product. Dosage: 200, 400 and 600 mg/d. The following symptoms have been evaluated: cough; dyspnea; bronchial breathings; expectoration; expectorate's viscosity; expectorate's volume. The data have been submitted to a statistic analyses, this research leads to the followings considerations. A dosage of 200 mg/d. is not significantly active on any on the considered parameters. The 400 mg dosage turns out to be noticeably more effective than the placebo on all parameters (except the difficulty in expectoration). A dosage of 600 mg/d. has a significant effect on all the measurable parameters. Finally, a 200 mg dosage of 4-carbomethoxythiazolidine three times a day results to be the best posology in the symptomatic treatment of the respiratory manifestations of chronic bronchitis.

  19. The skill components of a therapeutic chopsticks task and their relationship with hand function tests.

    Science.gov (United States)

    Chen, H M; Chang, J J

    1999-12-01

    Chopsticks are the primary tools used for eating and the physical movements of control are familiar to Chinese people. Chopsticks are easy to obtain in most rehabilitative settings. Occupational therapists often guide patients to practice miscellaneous chopsticks tasks to increase hand function in any case. The objective of this study was to investigate the skill components of the therapeutic chopsticks task and their relationship with hand function tests, and to identify clinical value. Eighty normal subjects (41 males and 39 females) whose age ranged from 17 to 26 years old participated in this study. Five standard hand function tests including three dexterity tests [Minnesota Rate of Manipulation Test (MRMT), Purdue Pegboard Test, and O'Connor Tweezer Dexterity Test (OTDT)], and two strength tests (Jamar Handgrip Test, and Pinchometer Test) were chosen to measure the dexterity and strength of hands. Additionally, the Test of Chopsticks Manipulation (TCM) was designed and used to assess the chopsticks manipulation skills. Subjects were tested with all the hand function tests and TCM in a random sequence. Results of six tests were obtained for each subject. Factor analysis showed that the skill components of TCM should be categorized into the "dexterity" component. In addition, a significant relationship (p < 0.05) was only seen between TCM and OTDT, there was no significant correlation between TCM and the other hand function tests. Findings in this study are valuable in setting the rehabilitation programs for patients with dexterity problems.

  20. 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.

  1. Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer.

    Science.gov (United States)

    Shen, Yao-An; Liu, Chang-Sheng; Chang, Yen-Hou; Chen, Po-Hung; He, Chun-Lin; Wu, Han-Chung; Chuang, Chi-Mu

    2015-04-28

    Currently, epithelial ovarian cancer is viewed as a heterogeneous disease with five major histological subtypes. Clear cell carcinoma represents a specific histological subtype of epithelial ovarian cancer that demonstrates more aggressive clinical behavior and drug resistance compared with other subtypes. Nevertheless, clear cell carcinoma is treated in the same manner as the other subtypes without any particular consideration to its unique clinical characteristics. To improve the therapeutic efficacy of the current liposomal doxorubicin approach for the treatment of clear cell carcinoma, we aimed to develop a novel peptide-conjugated liposomal doxorubicin to actively target this subtype. Two phage clones (OC-6 and OC-26) that specifically bound to clear cell carcinoma were isolated from a phage peptide display library after biopanning procedures. The peptide sequences were translated and aligned (OCSP-6 for OC-6, and OCSP-26 for OC-26, respectively). Peptide-conjugated nanoparticles demonstrated better tumor endocytosis and time-dependent gradual increase of intracellular drug uptake than non-targeting liposomal nanoparticles. Furthermore, peptide-conjugated liposomal doxorubicin better controlled tumors than did non-targeting liposomal doxorubicin. The current work may pave a new way for the development of drugs that target each subtype of epithelial ovarian cancer in the future. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. A randomized comparative trial on the therapeutic efficacy of topical aloe vera and Calendula officinalis on diaper dermatitis in children.

    Science.gov (United States)

    Panahi, Yunes; Sharif, Mohamad Reza; Sharif, Alireza; Beiraghdar, Fatemeh; Zahiri, Zahra; Amirchoopani, Golnoush; Marzony, Eisa Tahmasbpour; Sahebkar, Amirhossein

    2012-01-01

    Diaper dermatitis (DD) is a common inflammatory disorder among children and infants. The objective of the present randomized and double-blind trial was to compare the therapeutic efficacies of aloe vera cream and Calendula officinalis ointment on the frequency and severity of DD in children. Sixty-six infants with DD (aged Calendula ointment (n = 34). Infants were treated with these drugs 3 times a day for 10 days. The severity of dermatitis was graded at baseline as well as at the end of trial using a 5-point scale. The adverse effects of study medications were assessed during the trial. Although improvement in the severity of DD was observed in both treatment groups (P Calendula ointment had significantly fewer rash sites compared to aloe group (P = 0.001). No adverse effect was reported from either of the medications. The evidence from this study suggests that topical aloe and in particular Calendula could serve as safe and effective treatment for the treatment of diaper dermatitis in infants.

  3. Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts.

    Science.gov (United States)

    Moschetta, Michele; Pretto, Francesca; Berndt, Alexander; Galler, Kerstin; Richter, Petra; Bassi, Andrea; Oliva, Paolo; Micotti, Edoardo; Valbusa, Giovanni; Schwager, Kathrin; Kaspar, Manuela; Trachsel, Eveline; Kosmehl, Hartwig; Bani, Maria Rosa; Neri, Dario; Giavazzi, Raffaella

    2012-04-01

    The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma. ©2012 AACR.

  4. 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.

  5. Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease Avaliação do tratamento tripanossomicida em coorte de adultos chagásicos crônicos através de técnicas sorológicas convencionais e ELISA-F29

    Directory of Open Access Journals (Sweden)

    Diana Fabbro

    2013-06-01

    Full Text Available This work compared the time at which negative seroconversion was detected by conventional serology (CS and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.Este trabalho comparou os tempos de soroconversão negativos obtidos pela sorologia convencional (CS e teste ELISA-F29 em uma coorte de pacientes chagásicos crônicos tratados com nifurtimox ou benznidazol. Um estudo retrospectivo foi realizado com soro preservado de 66 adultos chagásicos assintomáticos com acompanhamento clínico e sorológico semestral ao longo de um seguimento médio de 23 anos. 29 pacientes receberam tratamento tripanossomicida e 37 outras permaneceram sem tratamento. O teste ELISA-F29 usou um ant

  6. 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, 1077...... in 94 patients (17.6%) tested compared with 89 events in 74 patients (13.9%) not tested (P = 0.095). CONCLUSION: Defibrillation efficacy during follow-up is not inferior in patients with a 40 J ICD implanted without DF testing. Defibrillation testing during first time ICD implantation should no longer...

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. [Efficacy of the therapeutic community model in the treatment of drug use-related problems: a systematic review].

    Science.gov (United States)

    Fiestas, Fabián; Ponce, Javier

    2012-03-01

    To summarize the scientific evidence about the efficacy of therapeutic communities (TC) to reduce substance use and related problems among people with substance use disorders. This systematic review builds from the work performed by Smith et al. (2006). We searched MEDLINE, EMBASE, Web of Science, Scielo, and LILACS for randomized trials that compare a TC with no treatment, a different type of treatment or another type of TC published from March 2004 to May 2011. 5 publications from 4 randomized trials were identified. All the studies had serious methodological limitations according to the CONSORT. The heterogeneity among studies did not allow for metaanalytic analysis to calculate pooled estimates. The primary analysis showed that, in prison, certain models of TC might be marginally superior to other types of treatments regarding levels of alcohol use, days in prison and re-incarceration rates. Also, evidence from a community setting (i.e., not in-prison) suggests that a community-based TC is not superior to an outpatient treatment model regarding levels of substance use, crime and unemployment at the 12-month follow-up. In general, there is no evidence to support superiority of TC over other more accessible and less costly types of treatment for drug use. However, in a prison context, TC might be of more benefit than other types of treatment. More research with solid experimental methodology is needed to add to the still weak body of evidence that supports the use of TC over other more affordable types of treatment for drug use disorders.

  10. Safety and efficacy of self-assembling bubble carriers stabilized with sodium dodecyl sulfate for oral delivery of therapeutic proteins.

    Science.gov (United States)

    Lin, Po-Yen; Chuang, Er-Yuan; Chiu, Yi-Hsuan; Chen, Hsin-Lung; Lin, Kun-Ju; Juang, Jyuhn-Huarng; Chiang, Ching-Hua; Mi, Fwu-Long; Sung, Hsing-Wen

    2017-08-10

    Sodium dodecyl sulfate (SDS) is generally regarded as a potent permeability enhancer in oral formulations; however, one concern related to the use of any permeation enhancer is its possible absorption of unwanted toxins during the period of epithelial permeability enhancement. In this work, the safety and efficacy of an SDS-containing bubble carrier system that is developed from an orally administered enteric-coated capsule are evaluated. The bubble carriers comprise diethylene triamine pentaacetic acid (DTPA) dianhydride, sodium bicarbonate (SBC), SDS, and insulin. Upon exposure to the intestinal fluid, DTPA dianhydride hydrolyzes to yield acids, and SBC rapidly reacts with these acids to generate CO 2 , producing bubble carriers, each containing a self-assembling water film. The hydrophilic insulin is entrapped in the self-assembled water film, which is stabilized by SDS. The SDS in the bubble carrier system can act as a dissolution enhancer in the dispersion of insulin molecules, as a surfactant that stabilizes the bubble carriers, as a protease inhibitor that protects the protein drug, and as a permeation enhancer that augments its oral bioavailability. Hence, a significant increase in the plasma insulin level and an excellent blood glucose-lowering response in diabetic rats are effectively achieved. Moreover, the enhancement of epithelial permeation by this SDS-containing formulation does not promote the absorption of intestinal endotoxins. The above facts indicate that the bubble carrier system that is stabilized by SDS can be used as a safe and potent carrier in the oral delivery of therapeutic proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

    2017-08-15

    Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

  12. Development of a standardized procedure for testing the efficacy of workplace cleansers.

    Science.gov (United States)

    Elsner, Peter; Seyfarth, Florian; Sonsmann, Flora; John, Swen-Malte; Diepgen, Thomas; Schliemann, Sibylle

    2014-01-01

    Occupational skin cleansing is a risk factor for cumulative irritant dermatitis. Standardized methods are required to assess the cleaning efficacy of occupational skin cleansers, allowing us to choose the optimal cleanser with minimal irritation for specific workplaces. To develop a standardized procedure for testing the cleaning efficacy of occupational skin cleansers. In this single-blind, randomized, monocentric clinical trial in 24 healthy volunteers, the cleaning efficacy of generic reference cleansers was assessed against standardized test dirts. The test procedure included standardized dirt application, standardized washing with an automated skin cleaning device, and quantification of the cleaning efficacy by chromametry. For two cleansers, reproducibility of the cleaning efficacy assessment was studied. Furthermore, the performance of two cleansers was compared with that of commercial skin cleansers. Cleaning factors ranged from 12% up to 97% for the respective model dirts. A high reproducibility of the washing and the assessment procedure could be shown. The comparison of the washing efficacies for two reference cleansers with those of commercial cleansers showed partly similar performances, but also a higher cleaning efficacy for some dirts of the reference cleansers. The testing procedure proved to be applicable to a wide spectrum of cleansers and model dirts. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Efficacy of permethrin insecticide tested against populations of ...

    African Journals Online (AJOL)

    Susceptibility test was conducted on the adult mosquitoes using 0.75 % permethrin impregnated paper embedded in World Health Organization (WHO) diagnostic test kit following standard procedure. Knockdown rate was recorded at 5 min interval for 1 hr and the final mortality was determined at 24 hr post exposure time.

  14. Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis

    NARCIS (Netherlands)

    Olesen, S.S.; Graversen, C.; Bouwense, S.A.W.; Goor, H. van; Wilder-Smith, O.H.G.; Drewes, A.M.

    2013-01-01

    BACKGROUND: A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. METHODS: Sixty-four patients

  15. Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing.

    Science.gov (United States)

    Placencio, Veronica R; DeClerck, Yves A

    2015-08-01

    Despite its function as an inhibitor of urokinase and tissue-type plasminogen activator (PA), PA inhibitor-1 (PAI-1) has a paradoxical protumorigenic role in cancer, promoting angiogenesis and tumor cell survival. In this review, we summarize preclinical evidence in support of the protumorigenic function of PAI-1 that has led to the testing of small-molecule PAI-1 inhibitors, initially developed as antithrombotic agents, in animal models of cancer. The review discusses the challenges and the opportunities that lay ahead to the development of efficacious and nontoxic PAI-1 inhibitors as anticancer agents. ©2015 American Association for Cancer Research.

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

    OpenAIRE

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

    2017-01-01

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

  17. Effect of treadmill testing and exercise training on self-efficacy in patients with heart failure.

    Science.gov (United States)

    Oka, Roberta K; DeMarco, Teresa; Haskell, William L

    2005-09-01

    Self-efficacy is a person's confidence in being able to successfully perform a specific activity or behavior. Self-efficacy has been shown to influence exercise capacity in patients post myocardial infarction, but has not been fully explored in patients with heart failure (HF). This study examined the impact of performance of a single treadmill exercise test and participation in a 3-month program of walking and resistance exercise on self-efficacy in HF patients. 24 patients were randomized to either a home-based walking and resistance exercise program or usual care for 3 months. Prior to enrollment into the exercise program all participants performed a single treadmill exercise test with respiratory gas analysis. Self-efficacy questionnaires were completed at 3 time points, 1) prior to performance of an exercise treadmill test; 2) immediately after completing an exercise test; and 3) at the end of a 3-month exercise program. Self-efficacy for walking (p=0.07), climbing (p=0.17), lifting (p=0.73) and general activity (p=0.15) did not improve after performance of a single treadmill exercise test and usual care. However, self-efficacy for walking increased after 3 months of a walking and resistance exercise program. (p=0.04). The findings from this study suggest that in patients with stable mild to moderate heart failure, self-efficacy is improved with participation in a home-based walking and endurance exercise program. Self-efficacy is not enhanced by performance of a single treadmill exercise test and usual care.

  18. Responsiveness of Various Exercise-Testing Protocols to Therapeutic Interventions in COPD

    Directory of Open Access Journals (Sweden)

    Benoit Borel

    2013-01-01

    Full Text Available Exercise intolerance is a key element in the pathophysiology and course of Chronic Obstructive Pulmonary Disease (COPD. As such, evaluating exercise tolerance has become an important part of the management of COPD. A wide variety of exercise-testing protocols is currently available, each protocol having its own strengths and weaknesses relative to their discriminative, methodological, and evaluative characteristics. This paper aims to review the responsiveness of several exercise-testing protocols used to evaluate the efficacy of pharmacological and nonpharmacological interventions to improve exercise tolerance in COPD. This will be done taking into account the minimally important difference, an important concept in the interpretation of the findings about responsiveness of exercise testing protocols. Among the currently available exercise-testing protocols (incremental, constant work rate, or self-paced, constant work rate exercise tests (cycle endurance test and endurance shuttle walking test emerge as the most responsive ones for detecting and quantifying changes in exercise capacity after an intervention in COPD.

  19. Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice.

    Science.gov (United States)

    van Wamel, Annemieke; Sontum, Per Christian; Healey, Andrew; Kvåle, Svein; Bush, Nigel; Bamber, Jeffrey; de Lange Davies, Catharina

    2016-08-28

    Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12mg/kg given i.p.), ACT induced a strong increase in therapeutic efficacy; 120days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%. In combination with Abraxane® (12mg paclitaxel/kg given i.v.), ACT induced a strong increase in the therapeutic efficacy; 60days after study start 100% of the animals were in stable, remission vs. 0% for the Abraxane® only group, 120days after study start 67% of the animals were in stable, complete remission vs. 0% for the Abraxane® only group. For the ACT+Abraxane group 100% of the animals were alive after 120days vs. 0% for the Abraxane® only group. Proof of concept for Acoustic Cluster Therapy has been demonstrated; ACT markedly increases the therapeutic efficacy of both paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Lisuride treatment of Alzheimer's disease. A preliminary placebo-controlled clinical trial of safety and therapeutic efficacy.

    Science.gov (United States)

    Claus, J J; de Koning, I; van Harskamp, F; Breteler, M M; Voet, B; Gutzmann, H; Dahlke, F; van der Cammen, T; Hofman, A

    1998-01-01

    In this article, the authors examine the effect of lisuride on 22 patients with probable Alzheimer's disease (NINCDS/ADRDA criteria) in a randomized double-blind, placebo-controlled, parallel group design. Ten patients received lisuride and 12 patients received placebo. Lisuride was administered in a dose-finding phase of four weeks and an efficacy phase of eight weeks, with a maximum dose of 0.3 mg daily. Outcome measures included global clinical impression, general cognitive function, mood, verbal and visual memory, attention, and psychomotor function. Average decline in Mini-Mental State Examination score after 12 weeks treatment was less often statistically significant in lisuride treated patients than in patients receiving a placebo (p < 0.05). Patients treated with lisuride improved their average total score and short-delay cued recall score on the California Verbal Learning Test, a test of verbal memory, whereas placebo-treated patients showed worse performance compared with baseline. These differences approached statistical significance, with p = 0.06 and p = 0.05, respectively. No other differences between the treatment groups were evident. The authors failed to find a consistent effect of lisuride on symptoms of Alzheimer's disease. However, this study's sample size was relatively small, and larger studies are needed to ascertain the treatment effects of serotonergic antagonists on Alzheimer's disease.

  1. Efficacy of a Direct Rapid Immunohistochemical Test (DRIT) For ...

    African Journals Online (AJOL)

    Rabies is an acute, infectious disease mostly transmitted through bites from an infected animal. Dogs majorly transmit rabies to humans. Human rabies is not curable once clinical signs commence, but can be prevented. The aim of this study was to find an appropriate diagnostic test suitable for use in Nigeria and other ...

  2. The evaluation of the therapeutic efficacy and side effects of a macromolecular dexamethasone prodrug in the collagen-induced arthritis mouse model

    Science.gov (United States)

    Quan, Lingdong; Zhang, Yijia; Dusad, Anand; Ren, Ke; Purdue, P. Edward; Goldring, Steven R.; Wang, Dong

    2015-01-01

    PURPOSE To investigate the efficacy and safety of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) in the collagen-induced arthritis (CIA) mouse model. METHODS HPMA copolymer labeled with a near infrared fluorescence (NIRF) dye was administered to mice with CIA to validate its passive targeting to inflamed joints and utility as a drug carrier system. The CIA mice were treated with P-Dex, dexamethasone (Dex) or saline and the therapeutic efficacy and skeletal toxicity evaluated using clinical scoring and micro-computed tomography (µ-CT). RESULTS The NIRF signal of the HPMA copolymer localized to arthritic joints consistent with its passive targeting to sites of inflammation. While the CIA mice responded more rapidly to P-Dex compared to Dex, the final clinical score and endpoint µ-CT analyses of localized bone erosions indicated that both single dose P-Dex and dose equivalent daily Dex led to comparable clinical efficacy after 30 days. µ-CT analysis of the proximal tibial metaphyses showed that P-Dex treatment was associated with significantly higher BMD and BV/TV compared to Dex and the saline control, consistent with reduced glucocorticoid (GC) skeletal toxicity. CONCLUSION These results validate the therapeutic efficacy of P-Dex in the CIA mouse model. P-Dex treatment averted the adverse effects of GC’s on systemic bone loss, supporting its utility in clinical development for the management of rheumatoid arthritis. PMID:26286188

  3. 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)....

  4. Strategy for Testing the Efficacy of Ballast Water Treatment Technologies

    Science.gov (United States)

    2003-12-01

    that make up each major grouping (Figure 1). It must be noted that the major endpoints of the tree (e.g., Porifera , Mollusca, Diatoms, Red Algae) are...dwelling marine invertebrates have planktonic stages (Barnes, 1974), which are assayed as zooplankton in BWT testing. Within the animal or zooplankton...community. 21 5.0 REFERENCES Barnes, R.D. (1974). Invertebrate Zoology. Third Edition. W.B. Saunders Co. Philadelphia. Bavykin, S.G., J.P. Akowski

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. A clinical study on the efficacy of natural therapeutic factors in Băile Tuşnad for the rehabilitation of post-stroke patients

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    Gabriela Dogaru

    2017-02-01

    Full Text Available Introduction. Stroke is one of the main causes of morbidity and mortality worldwide. Hypotonic carbonated mineral waters in Băile Tușnad are used for their peripheral and cerebral vasodilator effects in the prophylaxis, therapy and rehabilitation of cardiovascular patients. Objectives. The aim of the clinical study was to assess the efficacy of natural therapeutic factors in Băile Tușnad for continuing the rehabilitation of post-stroke patients in a spa and climatic resort for the treatment of cardiovascular diseases. Methods. The study included 30 patients with a history of stroke, aged between 56 and 89 years, with a mean age of 69 years, at the Facility Treatment of the Tușnad Spa Complex SA, in the period April-December 2014. The clinical study was a prospective longitudinal analysis. Of all 30 patients, 50% had ischemic stroke, 43% transient cerebral ischemic attack, and 7% hemorrhagic stroke. Hemiparesis was the most frequent clinical sign, followed by coordination, balance and gait disorders. Patients attended rehabilitation treatment consisting of kinesiotherapy, carbonated mineral water baths for 15 minutes, aerotherapy for 30 minutes daily, massotherapy, performed daily for 16 days. Each patient was clinically assessed before and after treatment based on the TINETTI Balance Scale, the 10-m walk test, the Motor Assessment Scale, the BARTHEL Index, adverse reactions. Results. At the end of treatment, an improvement in the walking speed, a statistically significant improvement in the quality of gait were observed, p < 0.05. Statistically significant results p<0.05 were also obtained for balance. On the Motor Assessment Scale, by comparing the means before and after treatment with the paired T test, a statistically significant value p<0.05 was obtained. When evaluating the patients’ performance for 10 activities of daily living depending on the need for external assistance, using the Barthel Index, the value of p <0.05 was

  8. Cultural Adaptation and Psychometric Testing of the Short Form of Iranian Childbirth Self Efficacy Inventory

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    Khorsandi, Mahboubeh; Asghari Jafarabadi, Mohammad; Jahani, Farzaneh; Rafiei, Mohammad

    2013-01-01

    Background: To assess maternal confidence in her ability to cope with labor, a measure of childbirth self efficacy is necessary. Objectives: This paper aims to assess the cultural adaptation and psychometric testing of the short form of childbirth self-efficacy Inventory among Iranian pregnant women. Patients and Methods: In this descriptive-methodological study, we investigated 383 Iranian pregnant women in the third trimester. They were recruited from the outpatient prenatal care clinic of ...

  9. 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

  10. Self-Efficacy, Gender and Trait Anxiety as Moderators of Test Anxiety

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    Onyeizugbo, Euckay U.

    2010-01-01

    Introduction: Test anxiety inhibits students from performing according to their full potential in academic setting. Objectives: This study investigated self-efficacy, gender and trait anxiety as moderators of test anxiety. Method: Two hundred and forty nine (249) psychology majors drawn from a university in Eastern Nigeria participated in the…

  11. Therapeutic efficacy of nutritional support by percutaneous endoscopic gastrostomy in critically ill patients: A self-control clinical trial.

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    Zhou, Fei; Gao, Ya-Ling; Liu, Zheng-Jin; Hu, Yi-Qun

    2017-01-01

    Percutaneous endoscopic gastrostomy (PEG) is a procedure to provide enteral nutrition for critically ill patients. It is commonly used in clinical practice; however, the widespread use of PEG is controversial. Our objective was to evaluate the therapeutic effect of nutritional support by PEG in these critically ill patients. A total of 64 critically ill patients including 41 males and 23 females (aged 23-84) were identified by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system during September 2004 to June 2012. The nutritional status before and after PEG was mainly assessed by the tricep skinfold thickness and serum albumin level. The nutritional status and pathological condition were assessed at 4, 8 and 12 weeks before and after PEG feeding. The assessment was according to the classical method of the human nutritional status. Follow-up was performed at one month, three months and 1.5 year after gastrostomy. Statistical analysis was performed by SPSS 11.5 software. The incidence of inhalation pneumonia and gastroesophageal regurgitation was compared by chi square (χ2) test. Pnutritional status and complications were improved after PEG in 55 patients (Pnutritional supply with no serious complications for critically ill patients.

  12. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

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    Tai-Chi Lin

    2017-01-01

    Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

  13. Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

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    Jovičić Bojan

    2013-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (CTG group. On the contralateral side 10 teeth with gingival recession were treated with the same surgical procedures but in combination with platelet-rich plasma (CTGPRP group. We measured the keratinized tissue width. For statistical significance we used the Student's t-test. Results. The study reveled a statistical significance in reducing vertical deepress of recession by both used treatments. Root deepness in CTG and CTG-PRP group was 90% and 93.5%, respectively. With both surgical techniques we achieved larger zone of keratinized gingiva but with a wide zone of keratinized tissue in CTG - the PRP group. Conclusion. The concept regeneration technique with PRP and with the stimulating influence of platele activated growth factors results in the regeneration of deep periodontal tissue as an important prerequisite for the successful treatment of gingival recession.

  14. Therapeutic Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium falciparum in Haiti after Many Decades of its Use

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

    2015-01-01

    Chloroquine (CQ) has been used for malaria treatment in Haiti for several decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a 42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was seasonal, with peak observations between October and January; 88% (107 of 121) of patients consented to participate. Sixty patients successfully completed the 42-day follow-up, whereas 47 patients withdrew consent or were lost to follow-up. The mean parasite density declined rapidly within the first few days after treatment. Seven patients did not clear their malaria infections and were clinically asymptomatic; therefore, they were considered late parasitological failures. About 90% (95% confidence interval = 84.20–97.90) of patients had no detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for recrudescence, reinfection, and CQ serum levels was not done in the seven patients, and therefore, their CQ resistance status is unresolved. CQ resistance surveillance by patient follow-up, in vitro drug sensitivity studies, and molecular markers is urgently needed in Haiti. PMID:25601993

  15. Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

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    Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

    2015-07-01

    We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

  16. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana.

    Science.gov (United States)

    Abuaku, Benjamin; Duah, Nancy; Quaye, Lydia; Quashie, Neils; Malm, Keziah; Bart-Plange, Constance; Koram, Kwadwo

    2016-01-05

    Case management based on prompt diagnosis and adequate treatment using artemisinin-based combination therapy (ACT) remains the main focus of malaria control in Ghana. As part of routine surveillance on the therapeutic efficacy of ACT in Ghana, the efficacy of amodiaquine-artesunate (AS-AQ) and artemether-lumefantrine (AL) were studied in six sentinel sites representing the forest and savannah zones of the country. Three sites representing the two ecological zones studied AS-AQ whilst the other three sites studied AL. In each site, the study was a one-arm prospective evaluation of the clinical, parasitological, and haematological responses to directly observed therapy for uncomplicated malaria with either AS-AQ or AL among children aged 6 months and 9 years. The WHO 2009 protocol for monitoring anti-malarial drug efficacy was used for the study between July 2013 and March 2014. Per-protocol analyses on day 28 showed an overall PCR-corrected cure rate of 100% for AS-AQ and 97.6% (95% CI 93.1, 99.5) for AL: 97.2% (95% CI 92.0, 99.4) in the forest zone and 100% in the savannah zone. Kaplan-Meier survival analysis showed similar outcomes. Prevalence of fever decreased by about 75% after the first day of treatment with each ACT in the two ecological zones. No child studied was parasitaemic on day 3, and gametocytaemia was generally maintained at low levels (<5%). Post-treatment mean haemoglobin concentrations significantly increased in the two ecological zones. Therapeutic efficacy of AS-AQ and AL remains over 90% in the forest and savannah zones of Ghana. Additionally, post-treatment parasitaemia on day 3 is rare suggesting that artemisinin is still efficacious in Ghana.

  17. Mammography self-efficacy scale and breast cancer fear scale: psychometric testing of the Turkish versions.

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    Secginli, Selda

    2012-01-01

    Self-efficacy for mammography and breast cancer fear are important determinants to mammography use. No tools to measure these beliefs of Turkish women have been validated. The purpose of this study was to assess the psychometric characteristics of the Turkish versions of the Mammography Self-Efficacy Scale (MSS-T) and the Champion Breast Cancer Fear Scale (CBCFS-T). Mammography Self-Efficacy Scale and Champion Breast Cancer Fear Scale were translated to Turkish language, validated by an expert panel, back translated, and tested. Cronbach α coefficients and item-total correlations were measured to evaluate the reliability of the scales. Exploratory factor analysis was used to estimate construct validity of the scales. Independent t tests, χ(2) tests, and logistic regression analyses were used to test theoretical relationships. Factor analysis yielded 1 factor for MSS-T and 2 factors for CBCFS-T with eigenvalues greater than 1. Internal consistency values presented acceptable Cronbach α levels of .90 for MSS-T and .90 for CBCFS-T, and test-retest reliability correlations were 0.56 for MSS-T and 0.60 for CBCFS-T. The MSS-T and CBCFS-T demonstrated acceptable preliminary values of reliability and validity. Further psychometric testing is recommended with women living in different regions of Turkey. The scales can offer insights to nurses and other healthcare professionals about mammography self-efficacy beliefs, emotional needs, and concerns of Turkish women related to breast cancer fear. The scales may be useful as process measures to assess the efficacy of interventions designed to alter self-efficacy and fear and subsequently improve the mammography rates.

  18. Reliability and validity testing of the Self-Efficacy for Functional Activities Scale.

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    Resnick, B

    1999-01-01

    Self-efficacy expectations for functional activities were defined operationally by having individuals rate their perceived judgment or confidence in their ability to perform each specific activity of daily living (ADL) (bathing, dressing, transferring, ambulating, and stair climbing) at a given point in time. The Self-Efficacy for Functional Activities (SEFA) scale initially included 27 items focusing on efficacy expectations related to performance of each ADL independently, with adaptive equipment, and with the help of another person. After initial pilaf testing the scale was revised to include 9 items which focused on efficacy expectations related to performance of each ADL independently, or with the help of another person. Two additional studies were done and provided some evidence for the reliability and validity of the SEFA when used with older adults.

  19. Is the time in therapeutic range using the ratio of tests equivalent to the Rosendaal method?

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    Caldeira, Daniel; Cruz, Inês; Morgado, Gonçalo; Stuart, Bruno; Gomes, Ana Catarina; Martins, Cristina; João, Isabel; Pereira, Hélder

    2015-12-01

    The percentage of time in therapeutic range (TTR) is a measure of anticoagulation quality with vitamin K antagonists (VKAs). The method most commonly used in clinical trials is the Rosendaal TTR. However, the application of this method in daily practice for clinical decision lacks appropriate instruments. We aimed to evaluate the percentage of tests within the target international normalized ratio (INR) (tests ratio) as a surrogate of Rosendaal TTR. We performed an observational and retrospective study to evaluate the TTR according to the Rosendaal method and tests ratio. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0. Three hundred and seventy-seven VKA-treated patients followed for a mean 1.3 years were evaluated. Rosendaal methold and tests ratio significantly correlated (Rho Spearman 0.88, P < 0.001), but the Bland-Altman plot evaluation showed a clinically relevant data dispersion [95% confidence interval (95% CI) -12.9 to 23.1] around a mean difference in TTR -5.1% using the tests ratio method. The linear regression Passing-Bablok confirmed the existence of significant data dispersion and systematic differences. The tests ratio less than 60% had a sensitivity of 91.6%, specificity of 72.3%, positive predictive value (PPV) of 72.2% and negative predictive value (NPV) of 91.6%, for the diagnosis of patients inadequately anticoagulated (Rosendaal TTR <60%). Tests ratio had a c-statistics of 0.94 (95% CI 0.91-0.96). Number of tests in 6 months had a c-statistics of 0.70 (95% CI 0.65-0.75). Tests ratio underestimated TTR in 5% and was not considered equivalent to Rosendaal TTR due to the high variability between methods. Nevertheless, the use of tests ratio less than 60% may be a reasonable option to detect inadequate anticoagulation, as it is a sensitive method and excluded most of the patients with adequate control.

  20. Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) in Treating Uncomplicated P. falciparum Malaria in Metehara, Eastern Ethiopia: Regulatory Clinical Study.

    Science.gov (United States)

    Nega, Desalegn; Assefa, Ashenafi; Mohamed, Hussein; Solomon, Hiwot; Woyessa, Adugna; Assefa, Yibeltal; Kebede, Amha; Kassa, Moges

    2016-01-01

    As per the WHO recommendation, the development of resistance by P. falciparum to most artemisinin combination therapies (ACTs) triggered the need for routine monitoring of the efficacy of the drugs every two years in all malaria endemic countries. Hence, this study was carried out to assess the therapeutic efficacy of Artemether-Lumefantrine (Coartem®) in treating the uncomplicated falciparum malaria, after 9 years of its introduction in the Metehara, Eastern Ethiopia. This is part of the therapeutic efficacy studies by the Federal Ministry of Health Ethiopia, which were conducted in regionally representative sentinel sites in the country from October 2014 to January 2015. Based on the study criteria set by WHO, febrile and malaria suspected outpatients in the health center were consecutively recruited to study. A standard six-dose regimen of AL was administered over three days and followed up for measuring therapeutic responses over 28 days. Data entry and analysis was done by using the WHO designed Excel spreadsheet and SPSS version 20 for Windows. Statistical significant was considered for P-value less than 0.05. Of the 91 patients enrolled, the day-28 analysis showed 83 adequate clinical and parasitological responses (ACPRs). Per protocol analysis, PCR-uncorrected & corrected cure rates of Coartem® among the study participants were 97.6% (95%CI: 93.6-99.5) and 98.8% (CI: 93.5-100%), respectively. No parasite detected on day 3 and onwards. Fever clearance was above 91% on day-3. Mean hemoglobin was significantly increased (Pmalaria in the study area. This study recommends further studies on drug toxicity, particularly on repeated cough and oral ulceration.

  1. Does Math Self-Efficacy Mediate the Effect of the Perceived Classroom Environment on Standardized Math Test Performance?

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    Fast, Lisa A.; Lewis, James L.; Bryant, Michael J.; Bocian, Kathleen A.; Cardullo, Richard A.; Rettig, Michael; Hammond, Kimberly A.

    2010-01-01

    We examined the effect of the perceived classroom environment on math self-efficacy and the effect of math self-efficacy on standardized math test performance. Upper elementary school students (N = 1,163) provided self-reports of their perceived math self-efficacy and the degree to which their math classroom environment was mastery oriented,…

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Yuya Yoshimoto

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

  4. Testing the Efficacy of Brief Multicultural Education Interventions in White College Students

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    Garriott, Patton O.; Reiter, Stephanie; Brownfield, Jenna

    2016-01-01

    This pilot study tested the overall and relative efficacy of 3 common approaches to multicultural education in a sample (N = 52) of White undergraduate students using a randomized controlled trial. Brief multicultural education interventions were delivered in the form of educational, social norming, and entertainment conditions. Affective (i.e.,…

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

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    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…

  6. 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…

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

    Science.gov (United States)

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

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

  8. Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy

    Science.gov (United States)

    2010-01-01

    Introduction The purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis. Methods Rats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts. Results A single systemic administration of P-Dex completely suppressed AA for >20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis. Conclusions P-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the

  9. 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.

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

    NARCIS (Netherlands)

    A. Kleijn (Anne); J.J. Kloezeman (Jenneke); E. Treffers-Westerlaken (Elike); G. Fulci (Giulia); S. Leenstra (Sieger); C.M.F. Dirven (Clemens); J.E.M.A. Debets (Reno); M.L.M. Lamfers (Martine)

    2014-01-01

    textabstractThe 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

  11. Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, R.; Chanda, N.; Zambre, A.; Upendran, A.; Katti, K.; Kulkarni, R. R.; Nune, S. K.; Casteel, S. W.; Smith, C. J.; Vimal, J.; Boote, E.; Robertson, J. D.; Kan, P.; Engelbrecht, H.; Watkinson, L. D.; Carmack, T. L.; Lever, J. R.; Cutler, C. S.; Caldwell, C.; Kannan, R.; Katti, K. V.

    2012-07-16

    Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechingallate( EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), will circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein provide unequivocal validation of our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from Au-198 isotope; the range of 198Au β-particle ( ~ 11 mm in tissue or ~1100 cell diameters) is sufficiently long to provide cross-fire effects of radiation dose delivered to cells within the prostate gland and short enough to minimize radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible 198AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed ~72% retention of 198AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 days demonstrating significant inhibition of tumor growth compared to controls. This innovative “green nanotechnological“approach serves as a basis for designing target specific antineoplastic agents. This novel intratumorally injectable 198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.

  12. Exploring the therapeutic efficacy of glioma vaccines based on allo- and syngeneic antigens and distinct immunological costimulation activators

    NARCIS (Netherlands)

    Stathopoulos, A.; Pretto, C.; Devillers, L.; Pierre, D.; Hofman, F.M.; Epstein, A.L.; Farghadani, H.; Kruse, C.A.; Jadus, M.R.; Chen, T.C.; Schijns, V.E.J.C.

    2012-01-01

    The efficacy of a various immunotherapeutic immunisation strategies for malignant glioma brain cancer was evaluated in the syngeneic CNS-1 Lewis rat glioma model. A prototype glioma cancer vaccine, which was composed of multivalent antigens derived from allogeneic and syngeneic cells and lysates,

  13. Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances tumor homing and therapeutic efficacy against melanoma.

    Science.gov (United States)

    Gunassekaran, Gowri Rangaswamy; Hong, Chae-Moon; Vadevoo, Sri Murugan Poongkavithai; Chi, Lianhua; Guruprasath, Padmanaban; Ahn, Byung-Cheol; Kim, Ha-Jeong; Kang, Tae Heung; Lee, Byungheon

    2018-01-08

    Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine. Compared to control CTLs, IL-4R-targeted CTLs showed higher binding to melanoma cells and in vivo tumor homing. They also exerted a more rapid and robust effector response, including increased cytokine secretion and cytotoxicity against melanoma cells and enhanced reprogramming of M2-type macrophages to M1-type macrophages. Moreover, IL-4R-targeted CTLs efficiently inhibited melanoma growth and reversed the immunosuppressive tumor microenvironment. These results suggest that non-genetically engineered CTLs targeting IL-4R have potential as an adoptive T cell therapy against melanoma. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Mkupasi, Ernatus Martin; Sikasunge, Chummy Sikalizyo; Ngowi, Helena Aminiel

    2013-01-01

    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...... 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...

  15. Preclinical efficacy testing in middle-aged rats: nicotinamide, a novel neuroprotectant, demonstrates diminished preclinical efficacy after controlled cortical impact.

    Science.gov (United States)

    Swan, Alicia A; Chandrashekar, Rupa; Beare, Jason; Hoane, Michael R

    2011-03-01

    Age is a consistent predictor of poor outcome following traumatic brain injury (TBI). Although the elderly population has one of the highest rates of TBI-related hospitalization and death, few preclinical studies have attempted to model and treat TBI in the aged population. Recent studies have indicated that nicotinamide (NAM), a soluble B-group vitamin, improved functional recovery in experimental models of TBI in young animals. The purpose of the present study was to examine the preclinical efficacy of NAM in middle-aged rats. Groups of middle-aged (14-month-old) rats were assigned to NAM (500 mg/kg or 50 mg/kg) or saline alone (1 mL/kg) treatment conditions, and received unilateral cortical contusion injuries (CCI) and injections at 1 h and 24 h following injury. The animals were tested on a variety of tasks to assess vestibulomotor (tapered beam) and cognitive performance (reference and working memory in the Morris water maze), and were evaluated for lesion size, blood-brain barrier compromise, astrocytic activation, and edema formation. In summary, the preclinical efficacy of NAM as a treatment following CCI in middle-aged rats differs from that previously documented in younger rats; while treatment with 50 mg/kg NAM appeared to have no effect, the 500-mg/kg dose worsened performance in middle-aged animals. Histological indicators demonstrated more nuanced group differences, indicating that NAM may positively impact some of the cellular cascades following injury, but were not substantial enough to improve functional recovery. These findings emphasize the need to examine potential treatments for TBI utilizing non-standard populations, and may explain why so many treatments have failed in clinical trials.

  16. Breath Ketone Testing: A New Biomarker for Diagnosis and Therapeutic Monitoring of Diabetic Ketosis

    Directory of Open Access Journals (Sweden)

    Yue Qiao

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  18. Cultural adaptation and psychometric testing of the short form of Iranian childbirth self efficacy inventory.

    Science.gov (United States)

    Khorsandi, Mahboubeh; Asghari Jafarabadi, Mohammad; Jahani, Farzaneh; Rafiei, Mohammad

    2013-11-01

    To assess maternal confidence in her ability to cope with labor, a measure of childbirth self efficacy is necessary. This paper aims to assess the cultural adaptation and psychometric testing of the short form of childbirth self-efficacy Inventory among Iranian pregnant women. In this descriptive-methodological study, we investigated 383 Iranian pregnant women in the third trimester. They were recruited from the outpatient prenatal care clinic of Taleghani Hospital and an urban health center from August to November 2011. Content validity was evaluated by a panel of specialists after adding two religious items. The women completed the inventory and the demographic characteristics questionnaire in an interview room. The internal consistency and construct validity were assessed by Cronbach's alpha and by exploratory and confirmatory factor analyses, respectively. Known group analysis on gravity assessed the discriminant validity of the measure. Content validity of the short form of the Iranian childbirth self-efficacy Inventory was confirmed. Factor analyses supported the conceptual two-factor structure of measure and hence supported its construct validity. The internal consistency was approved for the total scale and both subscales. The instrument differentiated prim gravid from multigravida women in the total scale and the efficacy expectancy subscale. Validity and reliability of the measure supports the use of the short form of the instrument as a clinical and research instrument in measuring childbirth self-efficacy among Iranian pregnant women.

  19. 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

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

    Science.gov (United States)

    Harrison, Robert A; Oluoch, George O; Ainsworth, Stuart; Alsolaiss, Jaffer; Bolton, Fiona; Arias, Ana-Silvia; Gutiérrez, José-María; Rowley, Paul; Kalya, Stephen; Ozwara, Hastings; Casewell, Nicholas R

    2017-10-01

    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 assays of the

  1. Curcumin improves the therapeutic efficacy of Listeriaat-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1

    Science.gov (United States)

    Singh, Manisha; Ramos, Ilyssa; Asafu-Adjei, Denise; Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Zang, Xingxing; Aggarwal, Bharat B; Gravekamp, Claudia

    2013-01-01

    Abstract Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeriaat), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeriaat-Mage-b and curcumin were tested. The first immunization strategy involved all Listeriaat-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeriaat-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeriaat-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeriaat-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression. This study is focused on improving cancer vaccination by reducing immune suppression. Here we demonstrate that curcumin improves vaccine

  2. Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine model of multiresistant Acinetobacter baumannii sepsis.

    Science.gov (United States)

    Cirioni, Oscar; Simonetti, Oriana; Pierpaoli, Elisa; Barucca, Alessandra; Ghiselli, Roberto; Orlando, Fiorenza; Pelloni, Maria; Trombettoni, Maria Michela Cappelletti; Guerrieri, Mario; Offidani, Annamaria; Giacometti, Andrea; Provinciali, Mauro

    2016-12-01

    We investigated the efficacy of colistin combined with teicoplanin or daptomycin in an experimental mouse model of multiresistant Acinetobacter baumannii infection. Animal received intraperitoneally 1ml saline containing 2×1010CFU of A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or teicoplanin were given by intraperitoneal administration 2h after bacterial challenge. A control group received sodium chloride solution. In the in vitro study A. baumannii showed to be susceptible only to colistin with MIC of 2mg/l. In the in vivo study, colistin alone showed a good antimicrobial efficacy. When combined with teicoplanin or daptomycin, colistin produced the lowest bacterial and the best survival rates. In immunological studies, when colistin was associated to daptomycin or teicoplanin, both the number and the cytotoxic activity of NK cells increased. In conclusion, colistin combined with teicoplanin or daptomycin may improve the therapy of multiresistant A. baumannii infection. Copyright © 2016. Published by Elsevier Inc.

  3. The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR

    OpenAIRE

    ?elik, Ahmet; ?zci, Servet; Kobat, Mehmet Ali; Ate?, Ahmet Hakan; ?akmak, Abd?lkadir; ?ak?ll?, Yasin; Y?lmaz, Mehmet Birhan; Zoghi, Mehdi

    2015-01-01

    Objective: The awareness, time in therapeutic range (TTR), and safety of warfarin therapy were investigated in the adult Turkish population. Methods: This multicenter prospective study includes 4987 patients using warfarin and involved regular international normalized ratio (INR) monitoring between January 1, 2014 and December 31, 2014. TTR was calculated according to F.R. Roosendaal?s algorithm. Awareness was evaluated based on the patients? knowledge of warfarin?s affect and food?drug inter...

  4. THERAPEUTIC EFFICACY OF PROBIOTICS AND SHORT CHAIN FATTY ACIDS IN GASTROINTESTINAL DISEASE: EVALUATION OF METABOLIC, HORMONAL AND INFLAMMATORY PARAMETERS

    OpenAIRE

    Simeoli, Raffaele

    2014-01-01

    In these three years we studied probiotics and postbiotics efficacy and their mechanism/s in preventing or limiting gastrointestinal diseases, such as hepatic steatosis and ulcerative colitis. On the basis of strength anatomical correlation between liver and gut, we wanted to observe if microorganisms present in gut and their postbiotic derivatives, the short chain fatty acids, were able to prevent or cure not only local intestinal disease but also to limit extraintestinal and systemic pathol...

  5. Therapeutic efficacy of digital music gastric electrical pacing for refractory functional dyspepsia concomitant with non-erosive reflux disease

    Directory of Open Access Journals (Sweden)

    Ya-mei RAN

    2015-04-01

    Full Text Available Objective To study the clinical efficacy of digital music gastric electrical pacing for refractory functional dyspepsia concomitant with non-erosive reflux disease, and its effects on mental health and life-quality of the patients. Methods According to the Rome Ⅲ criteria and Montreal consensus in diagnosis of gastroesophageal reflux disease, 50 patients with concomitant refractory functional dyspepsia and non-erosive reflux disease were recruited. The clinical efficacy of digital music gastric electrical pacing were evaluated using the score of clinical symptoms before treatment and 15 days after treatment, and the mental health and life-quality of patients were assessed using symptom checklist 90. Results Main symptoms, including upper abdominal pain, abdominal fullness, early satiety, belching, hiccup, nausea, heartburn, acid reflux (daytime, nocturnal acid reflux, loss of appetite and sleep, were significantly improved 15 days after treatment compared with those of pre-treatment, and there were statistically significant differences (all P<0.005. The significant response rate/response rate (efficacy rate were 59.0%/100.0%, 59.3%/96.3%, 47.0%/94.1%, 61.3%/96.8 %, 86.7%/100.0%, 80.0%/100.0%, 64.3%/92.9%, 73.7%/89.5%, 64.3%/85.7%, 90.0%/90.0%, 36.7%/93.3% respectively. After treatment for 15 days, the overall response rate of symptom relief was 94.4% in patients and the overall significant response rate was 65.7%. The symptom scores of somatization, obsessive-compulsiveness, depression, and anxiety were significantly improved, and the differences were statistically significant (all P<0.01. Conclusion The clinical efficacy of digital music gastric electrical pacing is significant for refractory functional dyspepsia concomitant with nonerosive reflux disease, and it is expected to be a new option for the treatment of this disease complex. DOI: 10.11855/j.issn.0577-7402.2015.03.08

  6. Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

    OpenAIRE

    Jovičić Bojan; Lazić Zoran; Nedić Milica; Matijević Stevo; Gostović-Špadijer Aleksandra

    2013-01-01

    Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with ging...

  7. Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

    Science.gov (United States)

    2014-01-01

    The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

  8. Mangiferin functionalized radioactive gold nanoparticles (MGF-198AuNPs) in prostate tumor therapy: green nanotechnology for production, in vivo tumor retention and evaluation of therapeutic efficacy.

    Science.gov (United States)

    Al-Yasiri, A Y; Khoobchandani, M; Cutler, C S; Watkinson, L; Carmack, T; Smith, C J; Kuchuk, M; Loyalka, S K; Lugão, A B; Katti, K V

    2017-10-31

    We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-198AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors (PC-3) of human prostate tumor origin induced in mice which overexpress this receptor subtype. Detailed in vivo therapeutic efficacy studies, through the intratumoral delivery of MGF-198AuNPs, show the retention of over 80% of the injected dose (ID) in prostate tumors up to 24 h. By three weeks post treatment, tumor volumes of the treated group of animals showed an over 5 fold reduction as compared to the control saline group. New opportunities for green nanotechnology and a new paradigm of using mangiferin as a tumor targeting agent in oncology for the application of MGF-198AuNPs in the treatment of cancer are discussed.

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

    Science.gov (United States)

    Oluoch, George O.; Ainsworth, Stuart; Alsolaiss, Jaffer; Bolton, Fiona; Arias, Ana-Silvia; Gutiérrez, José-María; Rowley, Paul; Kalya, Stephen; Ozwara, Hastings; Casewell, Nicholas R.

    2017-01-01

    Background 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. Methods 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. Findings 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

  10. Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: correlation with clinical study.

    Science.gov (United States)

    Aziz, Faisal; Yang, Xuesong; Wang, Xiaoqi; Yan, Qiu

    2015-07-01

    Helicobacter pylori (H. pylori) is a major causative agent for the induction of chronic gastritis, gastric ulcer and gastric cancer. Celecoxib (COX-2 inhibitor) inhibits gastric cancer cell proliferation, but with low treatment efficacy, limiting its applications. It is important to develop a better strategy to improve the efficacy of celecoxib. Lewis Y (LeY) is a difucosylated oligosaccharide, highly expressed in 60-90% of human epithelial cancers, including gastric cancer. We previously found that H. pylori infection was associated with high level of LeY in gastric cancer. Herein, we analyzed the correlation between H. pylori and cyclo-oxygenase-2 (COX-2), LeY, gastric markers (CA724 and GRN) in gastric patient's tissue and serum samples by IHC and ELISA. Furthermore, we treated the primary gastric cancer cells with celecoxib, anti-LeY antibody or the combination, and analyzed their therapeutic efficacy on CA724, GRN and COX-2 expression by Western blot, flow cytometry and ELISA. We found that gastric cancer had significantly high expression of H. pylori, COX-2, CA724, and GRN compared to gastric ulcers and chronic gastritis (P LeY (R--0.861), CA724 (R--0.714) and GRN (R--0.664) (P LeY antibody enhances the cancer cell proliferation inhibitory effects of celecoxib, which might be a new feasible way for gastric cancer therapy.

  11. [Improvisation with alcoholics. Test of a combination of creative and therapeutic procedures (author's transl)].

    Science.gov (United States)

    Vesenbeckh, W

    1980-02-01

    The article reports on Group Work making use of dancing improvisations and nonverbal interaction exercises as therapeutic media. The improvisation group is part of a stationary therapy programme for alcoholics. The therapeutic intention is to utilise the interactions of the group's members for therapeutic purposes. The improvisation suggestions and exercises should provoke nonverbal interactions which could then be discussed. The article describes the mode of action of the improvisation group on an individual member and on the whole group, the programme of this group, and the experiences made.

  12. Historic of therapeutic efficacy of albendazol sulphoxide administered in different routes, dosages and treatment schemes, against Taenia saginata cysticercus in cattle experimentally infected.

    Science.gov (United States)

    Lopes, Welber Daniel Zanetti; Cruz, Breno Cayeiro; Soares, Vando Edésio; Nunes, Jorge Luis N; Teixeira, Weslen Fabricio Pires; Maciel, Willian Giquelin; Buzzulini, Carolina; Pereira, João Carlos Melo; Felippelli, Gustavo; Soccol, Vanette Thomaz; de Oliveira, Gilson Pereira; da Costa, Alvimar José

    2014-02-01

    method for evaluating the efficacy of the aforementioned formulations against T. saginata cysticercus, it is possible to observe that, amongst the few molecules used in the chemotherapic treatment against T. saginata larvae, ALB-SO, administered in varied routes, dosages and treatment schemes, the studies conducted in 2008, 2009, and 2010, have a low therapeutic efficacy against C. bovis in Brazil, while ALBZ had insignificant efficacy values against T. saginata larvae parasitizing experimentally infected bovines. However, future studies using molecular biology will be necessary to assess whether the difference on the efficacy of the ALB-SO can be related to strain or another specific factor. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. A highly invasive human glioblastoma pre-clinical model for testing therapeutics

    Directory of Open Access Journals (Sweden)

    Cao Brian

    2008-12-01

    Full Text Available Abstract Animal models greatly facilitate understanding of cancer and importantly, serve pre-clinically for evaluating potential anti-cancer therapies. We developed an invasive orthotopic human glioblastoma multiforme (GBM mouse model that enables real-time tumor ultrasound imaging and pre-clinical evaluation of anti-neoplastic drugs such as 17-(allylamino-17-demethoxy geldanamycin (17AAG. Clinically, GBM metastasis rarely happen, but unexpectedly most human GBM tumor cell lines intrinsically possess metastatic potential. We used an experimental lung metastasis assay (ELM to enrich for metastatic cells and three of four commonly used GBM lines were highly metastatic after repeated ELM selection (M2. These GBM-M2 lines grew more aggressively orthotopically and all showed dramatic multifold increases in IL6, IL8, MCP-1 and GM-CSF expression, cytokines and factors that are associated with GBM and poor prognosis. DBM2 cells, which were derived from the DBTRG-05MG cell line were used to test the efficacy of 17AAG for treatment of intracranial tumors. The DMB2 orthotopic xenografts form highly invasive tumors with areas of central necrosis, vascular hyperplasia and intracranial dissemination. In addition, the orthotopic tumors caused osteolysis and the skull opening correlated to the tumor size, permitting the use of real-time ultrasound imaging to evaluate antitumor drug activity. We show that 17AAG significantly inhibits DBM2 tumor growth with significant drug responses in subcutaneous, lung and orthotopic tumor locations. This model has multiple unique features for investigating the pathobiology of intracranial tumor growth and for monitoring systemic and intracranial responses to antitumor agents.

  14. Standardized dirts for testing the efficacy of workplace cleaning products: validation of their workplace relevance.

    Science.gov (United States)

    Elsner, Peter; Seyfarth, Florian; Sonsmann, Flora; Strunk, Meike; John, Swen-Malte; Diepgen, Thomas; Schliemann, Sibylle

    2013-10-01

    In order to assess the cleaning efficacy of occupational skin cleansers, standardized test dirts mimicking the spectrum of skin soiling at dirty workplaces are necessary. To validate newly developed standardized test dirts (compliant with the EU Cosmetics Directive) for their occupational relevance. In this single-blinded, monocentric questionnaire-based clinical trial, 87 apprentices of three trades (household management; house painting and varnishing; and metal processing) evaluated the cleanability of six standardized test dirts in relation to their workplace dirts. In addition, they judged the similarity of the test dirts to actual dirts encountered in their working environments. Most of the household management participants assessed the hydrophilic model dirt ('mascara'), the lipophilic model dirt ('W/O cream') and a film-forming model dirt ('disperse paint') as best resembling the dirts found at their workplaces. Most of the painters and varnishers judged the filmogenic model dirts ('disperse paint' and 'acrylic paint') as best resembling the dirts found at their workplaces. For the metal workers, the lipophilic and paste-like model dirts were most similar to their workplace dirts. The spectrum of standardized test dirts developed represents well the dirts encountered at various workplaces. The test dirts may be useful in the development and in vivo efficacy testing of occupational skin cleansers. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.

    Science.gov (United States)

    Park, Seung-Hwan; Zheng, Jin Hai; Nguyen, Vu Hong; Jiang, Sheng-Nan; Kim, Dong-Yeon; Szardenings, Michael; Min, Jung Hyun; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

    2016-01-01

    Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect.

  16. Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia

    Directory of Open Access Journals (Sweden)

    Gebremedhin Kinfu

    2012-01-01

    Full Text Available Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in North Ethiopia. Methods. This prospective study was undertaken during August–November 2009 on 71 malaria patients that fulfilled the inclusion criteria set by the WHO. Patients were followed up for 28 days. Thick and thin blood films were prepared by Giemsa stain for microscopy to determine parasite density. A standard six-dose regimen of artemether-lumefantrine was administered over three days and was followed up with clinical and parasitological evaluations over 28 days. Results. The cure rate (ACPR was found to be high (97.2% in this study. The parasite and fever clearance time was also rapid. Artemether-lumefantrine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the study area showed 97.2% cure rate and only 2.8% failure rate. Conclusion. The result showed that the drug could continue as first line for the treatment of uncomplicated Plasmodium falciparum malaria in the study area. The efficacy of artemether-lumefantrine needs to be carefully monitored periodically in sentinel sites representing different areas of the country.

  17. Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety?

    Science.gov (United States)

    Murdaca, Giuseppe; Spanò, Francesca; Contatore, Miriam; Guastalla, Andrea; Penza, Elena; Magnani, Ottavia; Puppo, Francesco

    2016-01-01

    TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, and may be administered off-label to treat disseminated granuloma annulare systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. infliximab and adalimumab can induce the development of anti-infliximab (anti-IFX) and anti-adalimumab (anti-ADA) monoclonal antibodies (mAbs). In this review, we discuss the impact of anti-IFX and anti-ADA mAbs upon efficacy and safety of these biological agents. IgG/IgE neutralizing antibodies against infliximab and adalimumab decrease the possibility of achieving a minimal disease activity state or clinical remission, decrease drug survival, increase the need for doctors to prescribe a higher drug dosage and, finally, favor the occurrence of adverse events. Concomitant administration of DMARDs such as methotrexate or leflunomide prevents the development of neutralizing Abs against infliximab and adalimumab.

  18. Testing antimicrobial cleaner efficacy on gypsum wallboard contaminated with Stachybotrys chartarum.

    Science.gov (United States)

    Menetrez, Marc Y; Foarde, Karin K; Webber, Tricia D; Dean, Timothy R; Betancourt, Doris A

    2007-11-01

    Reducing occupant exposure to indoor mold 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 problem. The efficacy of antimicrobial cleaners to remove, eliminate or control mold growth on surfaces can easily be tested on non-porous surfaces. However, the testing of antimicrobial cleaner efficacy on porous surfaces, such as those found in the indoor environment such as gypsum board can be more complicated and prone to incorrect conclusions regarding residual organisms. The mold Stachybotrys chartarum has been found to be associated with idiopathic pulmonary hemorrhage in infants and has been studied for toxin production and its occurrence in water damaged buildings. Growth of S. chartarum on building materials such as gypsum wallboard has been frequently documented. Research to control S. chartarum growth using 13 separate antimicrobial cleaners on contaminated gypsum wallboard has been performed in laboratory testing. Popular brands of cleaning products were tested by following directions printed on the product packaging. A variety of gypsum wallboard surfaces were used to test these cleaning products at high relative humidity. The results indicate differences in antimicrobial efficacy for the six month period of testing. Results for the six types of GWB surfaces varied extensively. However, three cleaning products exhibited significantly better results than others. Lysol All-Purpose Cleaner-Orange Breeze (full strength) demonstrated results which ranked among the best in five of the six surfaces tested. Both Borax and Orange Glo Multipurpose Degreaser demonstrated results which ranked among the best in four of the six surfaces tested. The best antimicrobial cleaner to choose is often dependent on the type of surface to be cleaned of S. chartarum contamination. For Plain GWB, no paint, the

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

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

    Science.gov (United States)

    Whitley, Julie Anne; Rich, Bonnie L

    2008-12-01

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

  2. Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Dipti Deshpande

    Full Text Available Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/- mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

  3. Therapeutic mechanism and efficacy of the antibody-drug conjugate BAY 79-4620 targeting human carbonic anhydrase 9.

    Science.gov (United States)

    Petrul, Heike M; Schatz, Christoph A; Kopitz, Charlotte C; Adnane, Lila; McCabe, Timothy J; Trail, Pamela; Ha, Sha; Chang, Yong S; Voznesensky, Andrei; Ranges, Gerald; Tamburini, Paul P

    2012-02-01

    Carbonic anhydrase IX (CAIX) is a cell surface glycoprotein that is expressed in many different tumors and yet restricted in normal tissues to the gastrointestinal tract. It is upregulated by hypoxia and correlates with tumor grade and poor survival in several tumor indications. Monoclonal antibodies (mAb) with single digit nanomolar binding affinity for CAIX were derived by panning with the recombinant ectodomain of CAIX against the MorphoSys HUCAL Gold library of human Fabs. Highest affinity Fabs were converted to full-length IgGs and subjected to further characterization based upon their avidity and selectivity for CAIX, their capacity to undergo internalization in CAIX-expressing cell lines, and their selective localization to CAIX-positive human xenografted tumors when administered to mice as fluorescent conjugates. Through this selection process, the 3ee9 mAb was identified, which upon conjugation to monomethyl auristatin E through a self-immolative enzyme-cleavable linker yielded the potent and selective CAIX antibody-drug conjugate CAIX-ADC (BAY 79-4620). In preclinical human xenograft models in mice representing several tumor indications, BAY 79-4620 showed potent antitumor efficacy and in some models showed partial and complete tumor shrinkage even following a single dose. The mechanism of action was shown by histology to involve the sequelae of events typical of antitubulin agents. Efficacy in murine preclinical models correlated semiquantitatively, with CAIX expression levels as determined by immunohistochemistry and ELISA. These preclinical data collectively support the development of BAY 79-4620 for the treatment of cancer patients with CAIX overexpressing tumors.

  4. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model.

    Science.gov (United States)

    Wildenberg, Manon E; Levin, Alon D; Ceroni, Alessandro; Guo, Zhen; Koelink, Pim J; Hakvoort, Theodorus B M; Westera, Liset; Bloemendaal, Felicia M; Brandse, Johannan F; Simmons, Alison; D'Haens, Geert R; Ebner, Daniel; van den Brink, Gijs R

    2017-12-04

    Regulatory macrophages play a critical role in tissue repair, and we have previously shown that anti-tumour necrosis factor [TNF] antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the combination of anti-TNF and thiopurines, consistent with the enhanced efficacy of this combination therapy described in clinical trials. As thiopurines are unfortunately associated with significant side effects, we here aimed to identify alternatives for combination therapy with anti-TNF, using the macrophage induction model as a screening tool. Mixed lymphocyte reactions were treated with anti-TNF and a library of 1600 drug compounds. Induction of CD14+CD206+ macrophages was analysed by flow cytometry. Positive hits were validated in vitro and in the T cell transfer model of colitis. Among the 98 compounds potentiating the induction of regulatory macrophages by anti-TNF were six benzimidazoles, including albendazole. Albendazole treatment in the presence of anti-TNF resulted in alterations in the tubulin skeleton and signalling though AMPK, which was required for the enhanced induction. Combination therapy also increased expression levels of the immunoregulatory cytokine IL-10. In vivo, albendazole plus anti-TNF combination therapy was superior to monotherapy in a model of colitis, in terms of both induction of regulatory macrophages and improvement of clinical symptoms. Albendazole enhances the induction of regulatory macrophages by anti-TNF and potentiates clinical efficacy in murine colitis. Given its favourable safety profile, these data indicate that the repurposing of albendazole may be a novel option for anti-TNF combination therapy in IBD.

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

    Directory of Open Access Journals (Sweden)

    Bonglim Joo

    2017-05-01

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

  6. Defective dendritic cell generation from monocytes is a potential reason for poor therapeutic efficacy of interferon α2b (IFNα2b) in cervical cancer.

    Science.gov (United States)

    Roy, Soumyabrata; Goswami, Shyamal; Bose, Anamika; Goswami, Kuntal Kanti; Sarkar, Koustav; Chakraborty, Krishnendu; Chakraborty, Tathagata; Pal, Smarajit; Haldar, Atanu; Basu, Parthasarathi; Biswas, Jaydip; Baral, Rathindranath

    2011-10-01

    Despite being a pleiotropic cytokine, the therapeutic potential of interferon α2b (IFNα2b) is debatable. Thus, the need for identifying predictive marker(s) for patients who are most likely to benefit from the treatment is pivotal for avoiding the exposure of nonresponsive patients to the toxicity of the treatment. To account for the attenuated efficacy of the drug, we have verified its dendritic cell (DC) maturating ability from monocytes of cervical cancer stage IIIB (CaCx-IIIB) patients. First, we evaluated the status of monocytes from CaCx-IIIB and healthy women by conducting flow cytometric studies of various activation markers and a cytokine analysis by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Immature DCs were then generated from these monocytes and matured with low-dose IFNα2b (1500 units/mL). A functional and phenotypic comparative analysis of these matured DCs was performed by flow cytometric, proliferative, cytotoxic, and enzyme-linked immunosorbent assays. Our study shows that monocytes isolated from CaCx-IIIB are impaired, and in vitro maturation with IFNα2b did not significantly improve the functional repertoire of DCs generated from these monocytes in comparison with healthy controls. This impairment of monocytes might be a plausible reason for the attenuated efficacy of this drug alone in treating CaCx-IIIB patients, and this imbalance of immune parameters associated with the stage of malignancy might be considered an effective marker to design a proper therapeutic regimen. Copyright © 2011 Mosby, Inc. All rights reserved.

  7. Impact of defibrillation testing on predicted ICD shock efficacy: implications for clinical practice.

    Science.gov (United States)

    Smits, Karel; Virag, Nathalie; Swerdlow, Charles D

    2013-05-01

    Lack of consensus regarding defibrillation testing methods for implantable cardioverter-defibrillators relates to risks of repeated fibrillation episodes. To provide recommendations for testing protocols, repeating testing of patients with high defibrillation threshold (DFT), and interpreting testing after implantable cardioverter-defibrillator system revision. We constructed a computer model of defibrillation probability-of-success curves using data from 564 patients. Then, we compared 13 safety margin (SM) or DFT protocols in 50,000 simulated patients to identify those with the best balance of sensitivity and predictive value for detecting patients at high risk for failed defibrillation. Conditional retesting of patients with high DFT was simulated, both without and with revision that lowered defibrillation energy by one-third. SM protocols were more efficient than DFT protocols; 2/2 successes at 20 J or 1/1 at 16 J performed best. Patients who failed testing had a mean probability of defibrillation of 94% at 35 J, but great uncertainty regarding that probability (range 67.0%-100%). When they repeated testing, 62% passed, with 48% owing to regression to the mean. If system revision was performed before retesting, 84% passed; the fraction of patients at high risk reduced (4.7% to 2.7%, with 43% relative reduction); but 3.5% underwent unnecessary revisions. Testing and revision of patients with high DFT benefitted 2.5% of the patients. SM protocols are superior to DFT protocols for implant testing. For patients who fail testing, there is substantial uncertainty in defibrillation efficacy. After a system revision that does not alter defibrillation efficacy, 62% of these patients pass retesting. Copyright © 2013. Published by Elsevier Inc.

  8. Readying Students to Test: The Influence of Fear and Efficacy Appeals on Anxiety and Test Performance

    Science.gov (United States)

    von der Embse, Nathaniel P.; Schultz, Brandon K.; Draughn, Jeremy D.

    2015-01-01

    Educational accountability policies have led to a growth in the use of high-stakes examinations for a number of important educational decisions, including the evaluation of teacher effectiveness. As such, educators are under increasing pressure to raise student test performance. In an attempt to prepare students for a high-stakes exam, teachers…

  9. Pharmacokinetic variability, efficacy and tolerability of eslicarbazepine acetate-A national approach to the evaluation of therapeutic drug monitoring data and clinical outcome.

    Science.gov (United States)

    Svendsen, Torleiv; Brodtkorb, Eylert; Reimers, Arne; Molden, Espen; Sætre, Erik; Johannessen, Svein I; Johannessen Landmark, Cecilie

    2017-01-01

    Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory epilepsy. This retrospective observational study included TDM-data from the main laboratories and population data from the Norwegian Prescription Database in Norway, in addition to clinical data from medical records of adult patients using ESL for up to three years, whenever possible. TDM-data from 168 patients were utilized for assessment of pharmacokinetic variability, consisting of 71% of the total number of patients in Norway using ESL, 2011-14. Median daily dose of ESL was 800mg (range 400-1600mg), and median serum concentration of ESL was 53μmol/L (range 13-132μmol/L). Inter-patient variability of ESL was extensive, with 25-fold variability in concentration/dose ratios. Additional clinical data were available from 104 adult patients out of the 168, all with drug resistant focal epilepsy. After 1, 2 and 3 years follow-up, the retention rate of ESL was 83%, 72% and 64%, respectively. ESL was generally well tolerated as add-on treatment, but sedation, cognitive impairment and hyponatremia were reported. Hyponatremia (sodium <137mmol/L) was present in 36% of the patients, and lead to discontinuation in three. Pharmacokinetic variability of ESL was extensive and the demonstration of usefulness of TDM requires further studies. In patients with drug resistant focal Epilepsy, the high retention rate indicated good efficacy and tolerability. Hyponatremia was observed in one third of the patients. The present results point to a need for individualization of treatment and TDM may be useful. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Immediate therapeutic efficacy of low-density lipoprotein apheresis for drug-resistant nephrotic syndrome: evidence from the short-term results from the POLARIS Study.

    Science.gov (United States)

    Muso, Eri; Mune, Masatoshi; Hirano, Tsutomu; Hattori, Motoshi; Kimura, Kenjiro; Watanabe, Tsuyoshi; Yokoyama, Hitoshi; Sato, Hiroshi; Uchida, Shunya; Wada, Takashi; Shoji, Tetsuo; Yuzawa, Yukio; Takemura, Tsukasa; Sugiyama, Satoshi; Nishizawa, Yoshiki; Ogahara, Satoru; Yorioka, Noriaki; Sakai, Soichi; Ogura, Yosuke; Yukawa, Susumu; Iino, Yasuhiko; Imai, Enyu; Matsuo, Seiichi; Saito, Takao

    2015-06-01

    Hyperlipidemia is not merely a complication but a major exacerbating factor in longstanding nephrotic syndrome (NS). Low-density lipoprotein apheresis (LDL-A) has been reported to ameliorate dyslipidemia and induce rapid remission of NS. Several clinical studies have suggested the therapeutic efficacy of LDL-A, but the level of clinical evidence is insufficient. Therefore, a multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was initiated in Japan. Patients with drug-resistant NS were prospectively recruited into the study and treated with LDL-A in facilities that were registered in advance. In the POLARIS study design, the clinical data are to be followed up for 2 years. In the current study, we aimed at evaluating the short-term efficacy based on the treatment outcome of LDL-A immediately after completion of treatment. Along with rapid improvement of hyperlipidemia, LDL-A significantly improved proteinuria and hypoproteinemia after treatment. More than half of the patients showed remission of NS based on the urinary protein level at the completion of LDL-A. The duration of NS before the start of treatment was significantly shorter in patients who responded to LDL-A. An analysis of patients registered in the POLARIS study indicated that LDL-A has short-term efficacy for drug-resistant NS. Rapid relief of dyslipidemia by LDL-A may provide early remission in about half of the NS patients who are resistant to conventional medication. Completion of the POLARIS study may reveal additional long-term effects of LDL-A in these patients.

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

    Directory of Open Access Journals (Sweden)

    Bernard Waeber

    2008-02-01

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

  12. Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye

    Science.gov (United States)

    Lee, Jee Bum; Li, Ying; Choi, Ji Suk; Lee, Hyo Seok

    2016-01-01

    Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (P extracts improved clinical signs, decreased inflammation, and ameliorated oxidative stress marker and ROS production on the ocular surface of the EDE model mice. PMID:27313829

  13. The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR.

    Science.gov (United States)

    Çelik, Ahmet; İzci, Servet; Kobat, Mehmet Ali; Ateş, Ahmet Hakan; Çakmak, Abdülkadir; Çakıllı, Yasin; Yılmaz, Mehmet Birhan; Zoghi, Mehdi

    2016-08-01

    The awareness, time in therapeutic range (TTR), and safety of warfarin therapy were investigated in the adult Turkish population. This multicenter prospective study includes 4987 patients using warfarin and involved regular international normalized ratio (INR) monitoring between January 1, 2014 and December 31, 2014. TTR was calculated according to F.R. Roosendaal's algorithm. Awareness was evaluated based on the patients' knowledge of warfarin's affect and food-drug interactions. The mean TTR of patients was 49.52±22.93%. The patients with hypertension (55.3%), coronary artery disease (23.2%), congestive heart failure (24.5%), or smoking habit (20.8%) had significantly lower TTR levels than the others. Of the total number of patients, 42.6% had a mechanical valve, 38.4% had non-valvular atrial fibrillation (AF), and 19% had other indications for warfarin. Patients with other indications had lower TTR levels than those with mechanical valve and non-valvular AF (p=0.018). Warfarin awareness decreased in higher age groups. The knowledge of warfarin's food-drug interactions was 55%. People with higher warfarin awareness had higher TTR levels. Patients with ≤8 INR monitoring/year had lower TTR levels (46.4±25.3 vs. 51.1±21.3, respectively, pfood-drug interactions, and high rates of concomitant diseases.

  14. Porous quaternized chitosan nanoparticles containing paclitaxel nanocrystals improved therapeutic efficacy in non-small-cell lung cancer after oral administration.

    Science.gov (United States)

    Lv, Pi-Ping; Wei, Wei; Yue, Hua; Yang, Ting-Yuan; Wang, Lian-Yan; Ma, Guang-Hui

    2011-12-12

    Clinical application of paclitaxel (PTX) is limited because of its poor solubility in aqueous media. To overcome this hurdle, we devised an oral delivery system by encapsulating PTX into N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles. These nanoparticles were small (~130 nm), had a narrow size distribution, and displayed high loading efficiency owing to the homogeneous distribution of PTX nanocrystals. The matrix hydrophilicity and porous structure of the obtained nanoparticles accelerated their degradation and improved drug release. In vitro and in vivo transport experiments had proved that the presence of positive charges enhanced the intestinal permeability of these nanoparticles. Further in vitro experiment of cytotoxicity showed that the PTX-loaded HTCC nanoparticle (HTCC-NP:PTX) was more effective than native PTX owing to enhanced cellular uptake. Drug distribution in tissues and in vivo imaging studies confirmed the preferred accumulation of HTCC-NP:PTX in subcutaneous tumor tissue. Subsequent tumor xenograft assays demonstrated the promising therapeutic effect of HTCC-NP:PTX on inhibition of tumor growth and induction of apoptosis in tumor cells. Additional investigation into side effects revealed that HTCC-NP:PTX caused lower Cremophor EL-associated toxicities compared with Taxol. These results strongly supported the notion that HTCC nanoparticle (HTCC-NP) is a promising candidate as an oral carrier of PTX for cancer therapy.

  15. Relevance of the chronobiological and non-chronobiological actions of melatonin for enhancing therapeutic efficacy in neurodegenerative disorders.

    Science.gov (United States)

    Cecon, Erika; Markus, Regina P

    2011-05-01

    Melatonin is an indolamine with a large spectrum of functions that can be divided into chronobiotic and nonchronobiotic. Chronobiotic effects are mediated by the daily rhythm of melatonin in the plasma due to nocturnal pineal synthesis, whereas the melatonin produced by other cells, such as gastrointestinal and immune competent cells, is independent of the light/dark cycle and exert non-chronobiotic effects. The concentrations achieved by the two sources are significantly different, varying in the pM-nM range in the plasma, and may achieve concentrations in the mM range when released locally by activated immune-competent cells. Consequently, the effects of the melatonin produced in these two situations are distinct. Much has been reported about the beneficial response to exogenous melatonin administration in several pathological conditions. However, the relationship between the establishment of a disease and the state of the physiological activity of the pineal gland is still poorly understood. Here, we review the state of art in the modulation of pineal melatonin synthesis, relevant patents, and discuss its relationship with neurodegenerative disorders that involve a central inflammatory response, such as Alzheimer's disease, to suggest the putative relevance of new therapeutic protocols that replace this pineal hormone.

  16. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice.

    Science.gov (United States)

    Steinwede, Kathrin; Henken, Stefanie; Bohling, Jennifer; Maus, Regina; Ueberberg, Bianca; Brumshagen, Christina; Brincks, Erik L; Griffith, Thomas S; Welte, Tobias; Maus, Ulrich A

    2012-10-22

    Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae-induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail(-/-) mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.

  17. Efficacy of garlic (Allium sativum) extract applied as a therapeutic immersion treatment for Neobenedenia sp. management in aquaculture.

    Science.gov (United States)

    Militz, T A; Southgate, P C; Carton, A G; Hutson, K S

    2014-05-01

    Garlic, Allium sativum L., extract administered as a therapeutic bath was shown to have antiparasitic properties towards Neobenedenia sp. (MacCallum) (Platyhelminthes: Monogenea) infecting farmed barramundi, Lates calcarifer (Bloch). The effect of garlic extract (active component allicin) immersion on Neobenedenia sp. egg development, hatching success, oncomiracidia (larvae) longevity, infection success and juvenile Neobenedenia survival was examined and compared with freshwater and formalin immersion. Garlic extract was found to significantly impede hatching success (5% ± 5%) and oncomiracidia longevity (95% hatching success and mean oncomiracidia longevity of 37 ± 3 h. At much lower allicin concentrations (0.76 and 1.52 μL L(-1)), garlic extract also significantly reduced Neobenedenia infection success of L. calcarifer to 25% ± 4% and 11% ± 4%, respectively, compared with 55% ± 7% in the seawater control. Juvenile Neobenedenia attached to host fish proved to be highly resistant to allicin with 96% surviving 1-h immersion in 10 mL L(-1) (15.2 μL L(-1) allicin) of garlic extract. Allicin-containing garlic extracts show potential for development as a therapy to manage monogenean infections in intensive aquaculture with the greatest impact at the egg and larval stages. © 2013 John Wiley & Sons Ltd.

  18. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice

    Science.gov (United States)

    Steinwede, Kathrin; Henken, Stefanie; Bohling, Jennifer; Maus, Regina; Ueberberg, Bianca; Brumshagen, Christina; Brincks, Erik L.; Griffith, Thomas S.; Welte, Tobias

    2012-01-01

    Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae–induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail−/− mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae–infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option. PMID:23071253

  19. Therapeutic efficacy of guided tissue regeneration and connective tissue autotransplants with periosteum in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2008-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practice as an ethiological factor of periodontal diseases, and symptoms of the disease have caused the development of various surgical procedures and techniques of the reconstruction of periodontal defects. The aim of this study was to verify efficacy of surgical procedures that include connective tissue autotransplants with periosteum and guided tissue regeneration for the treatment of gingival recession. Methods. The study included 20 teet with gingival recession, Müller class II and III. Ten teeth with gingival recession were treated with resorptive membrane and coronary guided surgical flap (GTR group. On the contralateral side 10 teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (TVT group. We measured the degree of epithelial attachment (DEA, width of subgingival curettage (WGC and vertical deepness of recession (VDR. For statistical significance we used Student's ttest. Results. The study revealed statistical significance in reducing VDR by both used treatments. Root deepness in GTR and TVT group was 63.5%, and 90%, respectively. With both surgical techniques we achieved coronary dislocation of the epithelial attachment, larger zone of gingival curettage, and better oral hygiene. Conclusion. Current surgical techniques are effective in the regeneration of deep periodontal spaces and the treatment of gingival recession. Significantly better results were achieved with the used coronary guided surgical flap than with guided tissue regeneration.

  20. Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA-hIL12 fusion protein against Mycobacterium tuberculosis in mice.

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    Shanmin Zhao

    Full Text Available Tuberculosis (TB remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG, has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA and human interleukin 12 (hIL-12. Immune responses induced by the rMS in mice and protection against Mycobacterium tuberculosis (MTB were investigated. Administration of this novel rMS enhanced Th1-type cellular responses (IFN-γ and IL-2 in mice and reduced bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile, the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine also was significantly reduced. In conclusion, the rMS strain expressing the HBHA and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type response against TB, and the protective effect was equivalent to that of the conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load and alleviate histopathological damage in lungs of M. tuberculosis infected mice.

  1. 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

  2. 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.

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

    Science.gov (United States)

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

    2016-10-13

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

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

    Science.gov (United States)

    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…

  5. Pitfalls in efficacy testing – how important is the validation of neutralization of chlorhexidine digluconate?

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    Heisig Peter

    2008-12-01

    Full Text Available Abstract Background Effective neutralization of active agents is essential to obtain valid efficacy results, especially when non-volatile active agents like chlorhexidine digluconate (CHG are tested. The aim of this study was to determine an effective and non-toxic neutralizing mixture for a propan-1-ol solution containing 2% CHG. Methods Experiments were carried out according to ASTM E 1054-02. The neutralization capacity was tested separately with five challenge microorganisms in suspension, and with a rayon swab carrier. Either 0.5 mL of the antiseptic solution (suspension test or a saturated swab with the antiseptic solution (carrier test was added to tryptic soy broth containing neutralizing agents. After the samples were mixed, aliquots were spread immediately and after 3 h of storage at 2 – 8°C onto tryptic soy agar containing a neutralizing mixture. Results The neutralizer was, however, not consistently effective in the suspension test. Immediate spread yielded a valid neutralization with Staphylococcus aureus, Staphylococcus epidermidis and Corynebacterium jeikeium but not with Micrococcus luteus (p Candida albicans (p Staphylococcus epidermidis (p Corynebacterium jeikeium (p = 0.044. In the carrier test, the neutralizing mixture was found to be effective and non toxic to all challenge microorganisms when spread immediately. However, after 3 h storage of the neutralized active agents significant carry-over activity of CHG against Micrococcus luteus (p = 0.004; Tukey HSD was observed. Conclusion Without effective neutralization in the sampling fluid, non-volatile active ingredients will continue to reduce the number of surviving microorganisms after antiseptic treatment even if the sampling fluid is kept cold straight after testing. This can result in false-positive antiseptic efficacy data. Attention should be paid during the neutralization validation process to the amount of antiseptic solution, the storage time and to the choice of

  6. Investigation of the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma cells.

    Directory of Open Access Journals (Sweden)

    Nesrin Sabha

    Full Text Available Vestibular schwannomas (VS are a common posterior fossa brain tumor, and though benign can cause significant morbidity, particularly loss of hearing, tinnitus, vertigo and facial paralysis. The current treatment options for VS include microsurgical resection, stereotactic radiosurgery or close surveillance monitoring, with each treatment option carrying associated complications and morbidities. Most importantly, none of these options can definitively reverse hearing loss or tinnitus. Identification of a novel medical therapy, through the use of targeted molecular inhibition, is therefore a highly desirable treatment strategy that may minimize complications arising from both tumor and treatment and more importantly be suitable for patients whose options are limited with respect to surgical or radiosurgical interventions. In this study we chose to examine the effect of Nilotinib on VS. Nilotinib (Tasigna® is a second-generation receptor tyrosine kinase (RTK inhibitor with a target profile similar to that of imatinib (Gleevec®, but increased potency, decreased toxicity and greater cellular and tissue penetration. Nilotinib targets not only the BCR-ABL oncoprotein, but also platelet-derived growth factor (PDGF receptor signalling. In this preclinical study, the human NF2-null schwannoma cell line HEI-193 subjected to nilotinib inhibition demonstrated decreased viability, proliferation and anchorage-independent growth, and increased apoptosis. A daily dose of nilotinib for 5 days inhibited HEI-I93 proliferation at a clinically-relevant concentration in a dose-dependent manner (IC(50 3-5 µmol/L in PDGF-stimulated cells. These anti-tumorigenic effects of nilotinib were correlated to inhibited activation of PDGFR-α and PDGFR-β and major downstream signalling pathways. These experiments support a therapeutic potential for Nilotinib in VS.

  7. Therapeutic Efficacy of Cisplatin Thermosensitive Liposomes upon Mild Hyperthermia in C26 Tumor Bearing BALB/c Mice.

    Science.gov (United States)

    Alavizadeh, Seyedeh Hoda; Gheybi, Fatemeh; Nikpoor, Amin Reza; Badiee, Ali; Golmohammadzadeh, Shiva; Jaafari, Mahmoud Reza

    2017-03-06

    This study reports on the activity of thermosensitive liposomes (TSLs) incorporating different HSPC ratios in DPPC/MSPC/PEG2000-DSPE matrix (90/10/4) plus mild hyperthermia (HT) (42 °C). TSLs were loaded with a poorly membrane permeable anticancer drug, cisplatin, through the passive equilibration method. The addition of HSPC to the corresponding DPPC lipid matrix increased the transition temperature. In vitro data demonstrated >90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within 10 min at 42 °C, while other TSLs bearing HSPC showed greater stability. The plasma kinetics of cisplatin demonstrated higher cisplatin leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL) compared to other formulations. Indeed, increasing HSPC fraction in liposome bilayers significantly improved drug retention in blood. Though DPPC 90-LTSL plus one-step HT was expected to provide a unique drug release, the premature drug leakage as well as the likely wash-back of a great portion of drug into the blood circulation resulted in reduced survival. On the other hand, stabilized DPPC 30/HSPC 60/MSPC 10/PEG2000-DSPE 4 liposomes plus two-step HT greatly enhanced the survival of animals. In particular, the improved delivery of cisplatin through stabilized DPPC 30/HSPC 60/MSPC 10/PEG2000-DSPE 4 liposomes in two-step mild HT enhanced antitumor efficacy compared to other formulations. Thus, prolonged exposure of cancer cells to cisplatin through stabilized liposomes would be an efficient approach in improving the survival of animals.

  8. Geophysical variables and behavior: LXX. Testing electromagnetic explanations for a possible psychokinetic effect of therapeutic touch on germinating corn seed.

    Science.gov (United States)

    Bush, A M; Geist, C R

    1992-06-01

    Designs used to test claims for psychic healing of living systems not amenable to suggestion may produce artifact in the results when there is failure to control for other possible explanations. Some experimental methods in psychokinesis may produce electromagnetic field flux which could lead to erroneous conclusions. This study adds electrical and magnetic controls to assess their effect, leading to the conclusion that therapeutically touched corn seeds did not recover from saline injury significantly better than untreated controls.

  9. Ethanol injection of ornamental trees facilitates testing insecticide efficacy against ambrosia beetles (Coleoptera: Curculionidae: Scolytinae).

    Science.gov (United States)

    Reding, Michael E; Oliver, Jason B; Schultz, Peter B; Ranger, Christopher M; Youssef, Nadeer N

    2013-02-01

    Exotic ambrosia beetles are damaging pests in ornamental tree nurseries in North America. The species Xylosandrus crassiusculus (Motshulsky) and Xylosandrus germanus (Blandford) are especially problematic. Management of these pests relies on preventive treatments of insecticides. However, field tests of recommended materials on nursery trees have been limited because of unreliable attacks by ambrosia beetles on experimental trees. Ethanol-injection of trees was used to induce colonization by ambrosia beetles to evaluate insecticides and botanical formulations for preventing attacks by ambrosia beetles. Experiments were conducted in Ohio, Tennessee, and Virginia. Experimental trees injected with ethanol had more attacks by ambrosia beetles than uninjected control trees in all but one experiment. Xylosandrus crassiusculus and X. germanus colonized trees injected with ethanol. In most experiments, attack rates declined 8 d after ethanol-injection. Ethanol-injection induced sufficient pressure from ambrosia beetles to evaluate the efficacy of insecticides for preventing attacks. Trunk sprays of permethrin suppressed cumulative total attacks by ambrosia beetles in most tests. Trunk sprays of the botanical formulations Armorex and Veggie Pharm suppressed cumulative total attacks in Ohio. Armorex, Armorex + Permethrin, and Veggie Pharm + Permethrin suppressed attacks in Tennessee. The bifenthrin product Onyx suppressed establishment of X. germanus in one Ohio experiment, and cumulative total ambrosia beetle attacks in Virginia. Substrate drenches and trunk sprays of neonicotinoids, or trunk sprays of anthranilic diamides or tolfenpyrad were not effective. Ethanol-injection is effective for inducing attacks and ensuring pressure by ambrosia beetles for testing insecticide efficacy on ornamental trees.

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

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Chen, Xiang; Meyers, Joseph; Mulvilhill, John; Feyes, Denise; Edgehouse, Nancy; Duerk, Jeffrey L.; Pretlow, Thomas G.; Oleinick, Nancy L.

    2007-03-01

    We are developing in vivo small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center. In this study, we are developing magnetic resonance imaging (MRI) techniques that provide therapy monitoring and early assessment of tumor response to PDT. We generated human prostate cancer xenografts in athymic nude mice. For the imaging experiments, we used a highfield 9.4-T small animal MR scanner (Bruker Biospec). High-resolution MR images were acquired from the treated and control tumors pre- and post-PDT and 24 hr after PDT. We utilized multi-slice multi-echo (MSME) MR sequences. During imaging acquisitions, the animals were anesthetized with a continuous supply of 2% isoflurane in oxygen and were continuously monitored for respiration and temperature. After imaging experiments, we manually segmented the tumors on each image slice for quantitative image analyses. We computed three-dimensional T2 maps for the tumor regions from the MSME images. We plotted the histograms of the T2 maps for each tumor pre- and post-PDT and 24 hr after PDT. After the imaging and PDT experiments, we dissected the tumor tissues and used the histologic slides to validate the MR images. In this study, six mice with human prostate cancer tumors were imaged and treated at the Case Center for Imaging Research. The T2 values of treated tumors increased by 24 +/- 14% 24 hr after the therapy. The control tumors did not demonstrate significant changes of the T2 values. Inflammation and necrosis were observed within the treated tumors 24 hour after the treatment. Preliminary results show that Pc 4-PDT is effective for the treatment of human prostate cancer in mice. The small animal MR

  11. Human organ-on-a-chip BioMEMS devices for testing new diagnostic and therapeutic strategies

    Science.gov (United States)

    Leary, James F.; Key, Jaehong; Vidi, Pierre-Alexandre; Cooper, Christy L.; Kole, Ayeeshik; Reece, Lisa M.; Lelièvre, Sophie A.

    2013-03-01

    MEMS human "organs-on-a-chip" can be used to create model human organ systems for developing new diagnostic and therapeutic strategies. They represent a promising new strategy for rapid testing of new diagnostic and therapeutic approaches without the need for involving risks to human subjects. We are developing multicomponent, superparamagnetic and fluorescent nanoparticles as X-ray and MRI contrast agents for noninvasive multimodal imaging and for antibody- or peptide-targeted drug delivery to tumor and precancerous cells inside these artificial organ MEMS devices. Magnetic fields can be used to move the nanoparticles "upstream" to find their target cells in an organs-on-achip model of human ductal breast cancer. Theoretically, unbound nanoparticles can then be removed by reversing the magnetic field to give a greatly enhanced image of tumor cells within these artificial organ structures. Using branched PDMS microchannels and 3D tissue engineering of normal and malignant human breast cancer cells inside those MEMS channels, we can mimic the early stages of human ductal breast cancer with the goal to improve the sensitivity and resolution of mammography and MRI of very small tumors and test new strategies for treatments. Nanomedical systems can easily be imaged by multicolor confocal microscopy inside the artificial organs to test targeting and therapeutic responses including the differential viability of normal and tumor cells during treatments. Currently we are using 2-dimensional MEMS structures, but these studies can be extended to more complex 3D structures using new 3D printing technologies.

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

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    Abuaku Benjamin

    2012-11-01

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

  13. Human Stem Cell?Derived Endothelial?Hepatic Platform for Efficacy Testing of Vascular?Protective Metabolites from Nutraceuticals

    OpenAIRE

    Narmada, Balakrishnan Chakrapani; Goh, Yeek Teck; Li, Huan; Sinha, Sanjay; Yu, Hanry; Cheung, Christine

    2016-01-01

    Abstract Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small?molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem...

  14. 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.

  15. 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.

  16. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

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    Dulcinéa Maria Barbosa CAMPOS

    2016-01-01

    Full Text Available Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1 and on encysted larvae (G3 of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30 and a control group (G2-10; G4-10 with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals or 120 days after the inoculation (G3 animals. The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

  17. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE.

    Science.gov (United States)

    Campos, Dulcinéa Maria Barbosa; Barbosa, Alverne Passos; Oliveira, Jayrson Araújo; Barbosa, Carlos Augusto Lopes; Lobo, Tamara Flavia Correa; Silva, Luana Gabriella; Thomaz, Douglas Vieira; Peixoto, Josana de Castro

    2016-01-01

    Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

  18. HIV Testing Among Teens Attending Therapeutic Schools: Having a Personal Source of Information About HIV/AIDS Matters!

    Science.gov (United States)

    Swenson, Rebecca R; Houck, Christopher; Sarfati, David; Emerson, Erin; Donenberg, Geri; Brown, Larry K

    2015-06-01

    Being informed and using positive coping strategies are associated with engaging in health-promoting behaviors. We assessed whether the type of information source about HIV (personal or impersonal) and coping strategies (optimism, avoidance, or emotion-focused) are associated with HIV testing among adolescents attending therapeutic schools. Participants were 417 adolescents, ages 13-19, who attended one of 20 therapeutic day schools for emotionally/behaviorally disordered youth in two US cities (Providence, RI and Chicago, IL) and completed a baseline assessment for an HIV prevention study. Among adolescents in the study, 29% reported having been tested for HIV. Adolescents were more likely to have been tested if they were older, female, Hispanic, identified as non-heterosexual, came from lower SES households, and had recently had unprotected sex. Additionally, youth who endorsed greater use of optimistic thinking and emotion-focused coping, and who reported having been informed about HIV by more personal sources, were also more likely to have been tested for HIV. In a multivariate analysis, having had recent unprotected sex and having more personal sources of information about HIV/AIDS were independently associated with HIV testing. Study findings suggest that, controlling for sociodemographic background, sexual risk behavior, and coping strategy, HIV testing among adolescents with emotional and behavioral problems may be increased when adolescents learn about HIV/AIDS from personal sources such as their healthcare providers, family, and friends.

  19. Standardization of reporting procedures for nematicide efficacy testing: a research and extension perspective.

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    Mueller, J D; Noling, J W

    1996-12-01

    Nematicide tests reported in the Annals of Applied Nematology from 1991 to 1995 were reviewed and evaluated for 24 criteria. Most criteria such as soil type, nematode density, cultivar planted, test location, and nematicide applied were reported in more than adequate detail. Soil moisture content and temperature conditions during the test, field history of pesticide use, agronomic-horticultural production practices, and measurements of yield were reported less adequately. Many reports dealing with fumigant nematicides and application by irrigation had inadequate descriptions of rates and application methodology, Although areas for improvement exist, overall the published works in Annals of Applied Nematology are well-reported experiments. Pressure exists from several elements of hematology to "standarize" reporting procedures and test practices. Due to the diversity of crops, nematodes, nematicides, edaphic and environmental conditions that affect nematicide fate, nematode activity, plant growth, and subsequently nematicide efficacy, creation of a completely standardized format is improbable. More accurate reporting of some test criteria rather than standardization will allow better comparison between tests when results do not concur and allow future researchers to duplicate application rates and methodologies to determine the sources of discrepancies between tests, including environmental variations.

  20. Evaluation of therapeutic efficacy on combined use of clopidogrel and ozagrel sodium in the treatment of acute ischemic stroke

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    ZHAO Zhen

    2013-10-01

    Full Text Available Background Antiplatelet aggregation treatment has become a regular treatment of ischemic stroke. The affirmation of antiplatelet therapy is mainly derived from patients with clinical use, which can not provide the laboratory indexes for evaluation of a recognized accuracy. Studies have confirmed that the degree of platelet activation is associated with atherosclerosis and ischemic stroke, and recognized that both CD62p (α-platelet granule membrane glycoprotein and CD63 (lysosomal membrane glycoprotein were important indexes of platelet activation. This study aims to explore the differences of efficacy between combined use of clopidogrel and ozagrel sodium and monotherapy by aspirin in the treatment of acute ischemic stroke by investigating the expression of CD62p and CD63. Methods Flow cytometry was employed to detect CD62p and CD63 expression on circulating platelet in patients with ischemic stroke and normal control group. The positive rate of CD62p and CD63 was detected in patients with ischemic stroke who were treated with aspirin 0.15 g (single drug therapy and clopidogrel 75 mg + ozagrel sodium 80 mg (combination therapy before and after one and two weeks' treatment. National Institute of Health Stroke Scale (NIHSS scores were measured in patients with ischemic stroke at the same time in three periods respectively to evaluate the improvement of neural function. Results Platelet CD62p and CD63 positive expression rate in ischemic stroke group were higher than normal control group before treatment (P = 0.001, 0.032. CD62p and CD63 positive expression rate and NIHSS score were measured at different times, and the differences were statistically significant (F = 56.693, P = 0.000; F = 21.544, P = 0.000; F = 216.271, P = 0.000, respectively. Compared with before treatment, CD62p and CD63 positive expression rate and NIHSS score decreased significantly after treatment (P = 0.000, for all, but the differences between aspirin group and combination

  1. 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

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

    Science.gov (United States)

    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

  3. Therapeutic efficacy of c-kit-targeted radioimmunotherapy using 90Y-labeled anti-c-kit antibodies in a mouse model of small cell lung cancer.

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    Chisato Yoshida

    Full Text Available UNLABELLED: Small cell lung cancer (SCLC is an aggressive tumor and prognosis remains poor. Therefore, the development of more effective therapy is needed. We previously reported that high levels of an anti-c-kit antibody (12A8 accumulated in SCLC xenografts. In the present study, we evaluated the efficacy of two antibodies (12A8 and 67A2 for radioimmunotherapy (RIT of an SCLC mouse model by labeling with the (90Y isotope. METHODS: (111In- or (125I-labeled antibodies were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays in c-kit-expressing SY cells and in vivo by biodistribution in SY-bearing mice. Therapeutic efficacy of (90Y-labeled antibodies was evaluated in SY-bearing mice upto day 28 and histological analysis was conducted at day 7. RESULTS: [(111In]12A8 and [(111In]67A2 specifically bound to SY cells with high affinity (8.0 and 1.9 nM, respectively. 67A2 was internalized similar to 12A8. High levels of [(111In]12A8 and [(111In]67A2 accumulated in tumors, but not in major organs. [(111In]67A2 uptake by the tumor was 1.7 times higher than for [(111In]12A8. [(90Y]12A8, but not [(90Y]67A2, suppressed tumor growth in a dose-dependent manner. Tumors treated with 3.7 MBq of [(90Y]12A8, and 1.85 and 3.7 MBq of [(90Y]67A2 (absorbed doses were 21.0, 18.0 and 35.9 Gy, respectively almost completely disappeared approximately 2 weeks after injection, and regrowth was not observed except for in one mouse treated with 1.85 MBq [(90Y]67A2. The area of necrosis and fibrosis increased depending on the RIT effect. Apoptotic cell numbers increased with increased doses of [(90Y]12A8, whereas no dose-dependent increase was observed following [(90Y]67A2 treatment. Body weight was temporarily reduced but all mice tolerated the RIT experiments well. CONCLUSION: Treatment with [(90Y]12A8 and [(90Y]67A2 achieved a complete therapeutic response when SY tumors received an absorbed dose greater than 18 Gy and thus are

  4. Prevention of problematic gambling behavior among adolescents: testing the efficacy of an integrative intervention.

    Science.gov (United States)

    Donati, Maria Anna; Primi, Caterina; Chiesi, Francesca

    2014-12-01

    This study aimed at testing the efficacy of an integrative intervention to prevent adolescent problem gambling acting on a multidimensional set of factors including gambling related knowledge and misconceptions, economic perception of gambling, and superstitious thinking. A pre- and post-test design was performed with 181 Italian adolescents (64% boys; Mean age = 15.95) randomly assigned to two groups (Training and No Training). Results revealed that the intervention was effective in improving correct knowledge about gambling and reducing misconceptions, perception of gambling's profitability, and superstitious thinking. Except for misconceptions, these effects were obtained both in participants who were classified as Non-problem and At-Risk/Problem gamblers at the beginning of the intervention. Findings attested also that the training effects were stable over time, and that some changes in gambling behavior were produced. Findings were discussed referring to indications for future research aiming at confirming and extending the present results.

  5. The efficacy of the product Albendazole 10% of gastrointestinal nematode parasitism in sheep tested

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    Florin Stefan Hora

    2014-12-01

    Full Text Available Trichostrongylids are helminths of ruminants, located gastro intestinally. The disease generated by them is clinically manifested mainly by: diarrhea, weight loss, anemia and cachexia. They are produced by parasites belonging to the family Trichostrongylidae with genres: Ostertagia, Haemonchus, Trichostrongylus, Cooperia and Nematodirus. The study was accomplished in 2013 in Hidiseul de Sus village, Bihor County, and aimed to test the effectiveness of the Albendazole 10% in the natural infestations with gastrointestinal nematodes in sheep. Sheep studied consisted of 60 individuals from Turcana breed. Feces were examined by flotation method and to know the infestation level McMaster method was used, calculating the EPG value on day 0 of treatment, day 7 and day 14 post treatments. Anthelmintic efficacy (E% of the used product was of 97.03% after the FECRT formula. For a more meaningful expression it was used also Presidente and Borgsteede relations, where the result of efficiency for the tested product was 98% for both formulas.

  6. Therapeutic efficacy and safety of red blood cells treated with a chemical process (S-303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients.

    Science.gov (United States)

    Benjamin, Richard J; McCullough, Jeffrey; Mintz, Paul D; Snyder, Edward; Spotnitz, William D; Rizzo, Robert J; Wages, David; Lin, Jin-Sying; Wood, Lindsey; Corash, Laurence; Conlan, Maureen G

    2005-11-01

    A randomized, double-blind trial is reported of the clinical efficacy of red blood cells (RBCs) treated for pathogen inactivation with S-303, a synthetic labile alkylating agent. Patients undergoing complex cardiac surgeries were randomly assigned to receive either S-303-treated (test) or conventional (control) RBC transfusion during surgery and for 6 days thereafter. Efficacy was evaluated by comparing the occurrence of a composite primary endpoint of treatment-related morbidity (myocardial infarction and renal failure) and mortality. Two-hundred twenty-three patients were randomly assigned and 148 patients who received transfusions (74 with S-303-treated RBCs and 74 with control RBCs) were evaluable. The incidence of the primary endpoint was equivalent between the two groups (22 and 21% in the S-303-treated and control RBC groups, respectively). Secondary endpoints, including hemoglobin increment (mean, 1.4 vs. 1.5 g/dL), number of RBC transfusions (mean, 4.4 vs. 3.8 units), and other blood product support, were also comparable. The adverse event profile was similar between groups; however, patients who received S-303 RBCs were significantly more likely to develop constipation and less likely to suffer supraventricular extrasystoles. Four patients (2 test and 2 control) demonstrated positive indirect antiglobulin tests with reactivity for S-303 RBCs at one or more time points before or after transfusion, without evidence of hemolysis. S-303-treated and conventional RBCs were equivalent with respect to clinical efficacy and safety in supporting the transfusion needs of cardiac surgery patients. Investigations are under way to ascertain the significance of S-303 RBC antibodies and to prevent their occurrence.

  7. The Efficacy of Eye Movement Desensitization and Reprocessing Therapy Technique in the Treatment of Test Anxiety of College Students.

    Science.gov (United States)

    Enright, Matthew; Baldo, Tracy D.; Wykes, Scott D.

    2000-01-01

    Explores the efficacy of eye movement desensitization and reprocessing (EMDR) in the treatment of test anxiety. Thirty-five college students with test anxiety were assigned to either a treatment or delayed treatment control group. EMDR was shown to be effective in reducing overall test anxiety as well as "emotionality" and…

  8. The Jak2 inhibitor, G6, alleviates Jak2-V617F-mediated myeloproliferative neoplasia by providing significant therapeutic efficacy to the bone marrow.

    Science.gov (United States)

    Kirabo, Annet; Park, Sung O; Majumder, Anurima; Gali, Meghanath; Reinhard, Mary K; Wamsley, Heather L; Zhao, Zhizhuang Joe; Cogle, Christopher R; Bisht, Kirpal S; Keserü, György M; Sayeski, Peter P

    2011-11-01

    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 splenomegaly 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.

  9. The Jak2 Inhibitor, G6, Alleviates Jak2-V617F-Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow1

    Science.gov (United States)

    Kirabo, Annet; Park, Sung O; Majumder, Anurima; Gali, Meghanath; Reinhard, Mary K; Wamsley, Heather L; Zhao, Zhizhuang Joe; Cogle, Christopher R; Bisht, Kirpal S; Keserü, György M; Sayeski, Peter P

    2011-01-01

    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 splenomegaly 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. PMID:22131881

  10. The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis.

    Science.gov (United States)

    Huang, Fang-Yang; Huang, Bao-Tao; Wang, Peng-Ju; Zuo, Zhi-Liang; Heng, Yue; Xia, Tian-Li; Gui, Yi-Yue; Lv, Wen-Yu; Zhang, Chen; Liao, Yan-Biao; Liu, Wei; Chen, Mao; Zhu, Ye

    2015-11-01

    The benefit of therapeutic hypothermia (TH) to patients suffering out-of-hospital cardiac arrest (OHCA) has been well established. However, the effect of prehospital cooling remains unclear. We aimed to investigate the efficacy and safety of prehospital TH for OHCA patients by conducting a systematic review of randomised controlled trials (RCTs). The MEDLINE, EMbase and CENTRAL databases were searched for publications from inception to April 2015. RCTs that compared cooling with no cooling in a prehospital setting among adults with OHCA were eligible for inclusion. Random- and fixed-effect models were used depending on inter-study heterogeneity. Eight trials that recruited 2379 participants met the inclusion criteria. Prehospital TH was significantly associated with a lower temperature at admission (mean difference (MD) -0.94; 95% confidence interval (CI) -1.06 to -0.82). However, survival upon admission (Risk ratio (RR) 1.01, 95%CI 0.98-1.04), survival at discharge (RR 1.02, 95%CI 0.91-1.14), in-hospital survival (RR 1.05, 95%CI 0.92-1.19) and good neurological function recovery (RR 1.06, 95% CI 0.91-1.23) did not differ between the TH-treated and non-treated groups. Prehospital cooling increased the incidence of recurrent arrest (RR 1.23, 95%CI 1.02-1.48) and decreased the PH at admission (MD -0.04, 95%CI -0.07 to -0.02). Pulmonary oedema did not differ between the arms (RR 1.02, 95%CI 0.67-1.57). None of the potentially controversial issues (cooling methods, time of inducing TH, the proportion of continuing cooling in hospital, actual prehospital infusion volume and primary cardiac rhythms) affected the efficacy. Evidence does not support the administration of prehospital TH to patients with OHCA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Vandervert, Larry

    2015-01-01

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

  13. The Diagnostic, Prognostic, and Therapeutic Utility of Molecular Testing in a Patient with Waldenstrom's Macroglobulinemia.

    Science.gov (United States)

    Chin, Collin K; Leslie, Connull; Grove, Carolyn S; Van Vliet, Chris; Cheah, Chan Yoon

    2017-09-22

    The application of molecular genomics and our understanding of its clinical implications in the diagnosis, prognostication and treatment of lymphoproliferative disorders has rapidly evolved over the past few years. Of particular importance are indolent B-cell malignancies where tumour cell survival and proliferation are commonly driven by mutations involving the B-cell receptor and downstream signalling pathways. In addition, the increasing number of novel therapies and targeted agents have provided clinicians with new therapeutic options with the aim of exploiting such mutations. In this case report, we highlight one such success story involving the diagnostic impact of the MYD88L265P mutation in Waldenstrom's macroglobulinemia (WM), its prognostic implications and effect on choice of therapy in the era of novel therapies.

  14. Experimental Research on Therapeutic Efficacy of Traditional Chinese Medicine Shengjing Capsule Extracts in Treating Spermatogenesis Impairment Induced by Oxidative Stress.

    Science.gov (United States)

    Zhou, Shaohu; Wen, Zhiwei; Liang, Aijun; Zhang, Shuting

    2016-01-05

    To investigate antioxidant effects of traditional Chinese Shengjing capsule extracts (sperm-producing capsule, with functions of tonifying kidney and invigorating kidney essence) on testes, epididymides, and sperms of rats. We randomly divided 50 rats into 5 groups. G1: normal control group (treated with saline); G2: cadmium chloride group; G3: cadmium chloride+ low doses of drugs; G4: cadmium chloride + medium doses of drugs; and G5: cadmium chloride + high doses of drugs (equivalent dose: 0.45 g/kg). In addition to the normal control group, the other 4 groups started receiving intraperitoneal injection of cadmium chloride (1 mg/kg, i.p.). Testicular glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and malondialdehyde aldehyde (MDA) were measured by ELISA; epididymis histopathological examination was performed; testis serum testosterone (T) was measured; specimens of the epididymal semen were analyzed for sperm concentration, morphology, vitality, and DNA fragmentation rate. Sperm count and activity of rats in the model control group decreased significantly; their MDA concentration of testicular and epididymal homogenates increased greatly; while the vitality of SOD and GSH-Px dropped sharply. All indexes mentioned above were significantly different from those of the blank control group (P<0.05); the sperm count and activity of rats treated with Shengjing capsule (sperm-producing capsule) decreased, but were still significantly higher than those of the model group (P<0.05). MDA level of rats treated with Shengjing capsule were significantly lower than that of the model group (P<0.05), while their SOD and GSH-Px activity were significantly higher than the model group (P<0.05). The normal morphology rate and DNA integrity rate of groups treated with Shengjing capsule were significantly higher than those of the model group (P<0.05). Shengjing can enhance the activity of antioxidant enzymes and inhibit oxidative stress. It can also repair testicular and

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

    Science.gov (United States)

    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 grid, we delineated katydid hotspots in two ways: (1) count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2) score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species' natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms.

  16. Intraosseous infusion of ice cold saline is less efficacious than intravenous infusion for induction of mild therapeutic hypothermia in a swine model of cardiac arrest.

    Science.gov (United States)

    Larabee, Todd M; Campbell, Jenny A; Severyn, Fred A; Little, Charles M

    2011-05-01

    Intravenous (IV) infusion of ice cold saline is an effective method to initiate induction of mild therapeutic hypothermia (MTH) following resuscitation from out-of-hospital cardiac arrest (OOHCA). Intraosseous (IO) infusion of cold saline may be an alternative method to induce MTH. The goal of this study was to determine if IO infusion of cold saline is a comparable alternative to IV infusion for inducing MTH in a laboratory swine model of cardiac arrest. Ten mixed breed swine were resuscitated from cardiac arrest and randomized post-resuscitation to infusion with ice cold saline using either IO (n = 5) or IV (n = 5) access. The study endpoints were either a goal esophageal temperature of 34 °C or the elapse of a 30 min time period, simulating a long prehospital transport. Four of five pigs in the IV infusion group achieved goal temperature within 30 min compared to 0/5 in the IO infusion group (p = 0.048). The mean esophageal temperature change was significantly higher in the IV group when compared to the IO group (p cold saline is an efficacious method to achieve MTH in this swine model of cardiac arrest. Furthermore, IO infusion of cold saline is not sufficient to induce MTH in the time routinely available in the prehospital setting following OOHCA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    2012-02-01

    Full Text Available Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds, genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach.This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, “Δ24DoubleRGD.” Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD motif incorporated into both fiber and capsid protein IX (pIX and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.

  18. Efficacy of Percutaneous Electrical Nerve Stimulation and Therapeutic Exercise for Older Adults with Chronic Low Back Pain: A Randomized Controlled Trial

    Science.gov (United States)

    Weiner, Debra K.; Perera, Subashan; Rudy, Thomas E.; Glick, Ronald M.; Shenoy, Sonali; Delitto, Anthony

    2008-01-01

    Chronic low back pain (CLBP) in older adults may be disabling and therapeutically challenging, largely because of the inefficacy and/or morbidity associated with traditional pain treatment. We conducted a randomized controlled trial in 200 men and women ≥ age 65 with CLBP to evaluate the efficacy of percutaneous electrical nerve stimulation (PENS) with and without general conditioning and aerobic exercise (GCAE), for reducing pain and improving physical function. Participants were randomized to receive 1) PENS, 2) control-PENS (brief electrical stimulation to control for treatment expectancy), 3) PENS + GCAE, or 4) control-PENS + GCAE, twice a week for 6 weeks. All four groups experienced significantly reduced pain (range −2.3 to −4.1 on the McGill Pain Questionnaire short form), improved self-reported disability (range −2.1 to −3.0 on Roland scale) and improved gait velocity (0.04–0.07 m/sec), sustained at 6 months. The GCAE groups experienced significantly fewer fear avoidance beliefs immediately post-intervention and at 6 months than non-GCAE groups. There were no significant side effects. Since brief electrical stimulation (i.e., control-PENS) facilitated comparably reduced pain and improved function at 6 months as compared with PENS, the exact dose of electrical stimulation required for analgesia cannot be determined. GCAE was more effective than PENS alone in reducing fear avoidance beliefs, but not in reducing pain or improving physical function. PMID:18930352

  19. Comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis in dairy buffaloes.

    Science.gov (United States)

    Khan, Aimal; Ahmed, Tanveer; Rizwan, Muhammad; Khan, Najma

    2017-12-15

    To investigate the comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis, a total of 30 subclinical mastitis positive buffaloes out of 194 lactating buffaloes were divided into 3 equal groups viz. A, B and C. Group A was treated with procaine penicillin, group B was treated with Phyllanthus emblica fruit extract and group C was served as control for 5 days respectively. The collected milk samples were subjected to the treatment trials before and after the treatment at day 0, 7th and 14th day aseptically. The evaluation parameters were bacteriological cure rate, milk pH, milk yield. The percentage cure rate of sub-clinically mastitic quarters in group A, B and C were 80.95%, 64.7% and 22.22% at day 14 respectively. The quarter based bacteriological cure rate was highest in group A (80.95%) followed by group B (64.7%) and group C (22.22%). The pH was significant (P > .05) in group A, B and C at day 0, 7 and 14. It is concluded that Phyllanthus emblica fruit extract is an inexpensive source in the treatment of subclinical mastitis in dairy buffaloes and can be used as an alternative to antibiotic therapy as for procaine penicillin. Copyright © 2017. Published by Elsevier Ltd.

  20. Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.

    Science.gov (United States)

    Dong, Yaqiong; Yang, Jun; Liu, Hongmei; Wang, Tianyou; Tang, Suoqin; Zhang, Jinchao; Zhang, Xin

    2015-01-01

    To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.

  1. 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.)

  2. Genetic tests to evaluate prognosis and predict therapeutic response in acute myeloid leukemia.

    Science.gov (United States)

    Gulley, Margaret L; Shea, Thomas C; Fedoriw, Yuri

    2010-01-01

    Management of patients with acute myeloid leukemia relies on genetic tests that inform diagnosis and prognosis, predict response to therapy, and measure minimal residual disease. The value of genetics is reinforced in the revised 2008 World Health Organization acute myeloid leukemia classification scheme. The various analytic procedures-karyotype, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, DNA sequencing, and microarray technology-each have advantages in certain clinical settings, and understanding their relative merits assists in specimen allocation and in effective utilization of health care resources. Karyotype and array technology represent genome-wide screens, whereas the other methods target specific prognostic features such as t(15;17) PML-RARA, t(8;21) RUNX1-RUNX1T1, inv(16) CBFB-MYH11, 11q23 MLL rearrangement, FLT3 internal tandem duplication, or NPM1 mutation. New biomarkers and pharmacogenetic tests are emerging. The pathologist's expertise is critical in 1) consulting with clinicians about test selection as well as specimen collection and handling; 2) allocating tissue for immediate testing and preserving the remaining specimen for any downstream testing that is indicated once morphology and other pertinent test results are known; 3) performing tests that maximize outcome based on the strengths and limitations of each assay in each available specimen type; and 4) interpreting and conveying results to the rest of the health care team in a format that facilitates clinical management. Acute myeloid leukemia leads the way for modern molecular medicine.

  3. Testing the Therapeutic Potential of Doxycycline in a Drosophila melanogaster Model of Alzheimer Disease*

    Science.gov (United States)

    Costa, Rita; Speretta, Elena; Crowther, Damian C.; Cardoso, Isabel

    2011-01-01

    Therapies for Alzheimer disease that reduce the production of pathogenic amyloid β (Aβ) peptides have been associated with a range of unwanted effects. For this reason, alternative strategies that promote the clearance of the peptide by preventing its aggregation and deposition in the brain have been favored. In this context we have studied doxycycline, a member of the tetracycline family of antibiotics that has shown neuroprotective effects in a number of models of neurodegenerative disease. We investigated the neuroprotective potential of doxycycline in a Drosophila model of Aβ toxicity and sought to correlate any effects with the aggregation state of the peptide. We found that administration of doxycycline to Aβ42-expressing flies did not improve their lifespan but was able to slow the progression of their locomotor deficits. We also measured the rough eye phenotype of transgenic flies expressing the E22G variant of Aβ42 and showed that doxycycline administration partially rescued the toxicity of Aβ in the developing eye. We correlated these in vivo effects with in vitro observations using transmission electron microscopy, dynamic light scattering, and thioflavin T binding. We found that doxycycline prevents Aβ fibrillization and favors the generation of smaller, non-amyloid structures that were non-toxic as determined by the lack of caspase 3 activation in a neuroblastoma cell line. Our confirmation that doxycycline can prevent amyloid β toxicity both in vitro and in vivo supports its therapeutic potential in AD. PMID:21998304

  4. Mitigating Physiological Responses to Layoff Threat: An Experimental Test of the Efficacy of Two Coping Interventions

    Directory of Open Access Journals (Sweden)

    Tahira M. Probst

    2016-03-01

    Full Text Available The purpose of the current study was to assess real-time physiological reactions to the threat of layoffs and to determine whether the use of an emotion-focused vs. problem-focused coping intervention would be more efficacious in attenuating these physiological reactions. A 2 (coping intervention × 4 (within-subjects time points mixed experimental design was used to test the hypotheses. Eighty-four undergraduates participated in this laboratory experiment during which their galvanic skin response (GSR and heart rate (HR were continuously monitored. Analyses indicate that individuals instructed to utilize an emotion-focused coping strategy experienced a significantly greater decline in their GSR compared to those utilizing the problem-focused coping method. Results suggest organizations conducting layoffs might focus first on dealing with the emotional aftermath of downsizing before focusing on problem-solving tasks, such as resume writing and other traditional outplacement activities.

  5. Mitigating Physiological Responses to Layoff Threat: An Experimental Test of the Efficacy of Two Coping Interventions.

    Science.gov (United States)

    Probst, Tahira M; Jiang, Lixin

    2016-03-18

    The purpose of the current study was to assess real-time physiological reactions to the threat of layoffs and to determine whether the use of an emotion-focused vs. problem-focused coping intervention would be more efficacious in attenuating these physiological reactions. A 2 (coping intervention) × 4 (within-subjects time points) mixed experimental design was used to test the hypotheses. Eighty-four undergraduates participated in this laboratory experiment during which their galvanic skin response (GSR) and heart rate (HR) were continuously monitored. Analyses indicate that individuals instructed to utilize an emotion-focused coping strategy experienced a significantly greater decline in their GSR compared to those utilizing the problem-focused coping method. Results suggest organizations conducting layoffs might focus first on dealing with the emotional aftermath of downsizing before focusing on problem-solving tasks, such as resume writing and other traditional outplacement activities.

  6. Differences in therapeutic consequences of exercise testing in a rural and an urban Danish county

    DEFF Research Database (Denmark)

    Niemann, T.; Nielsen, T.T.; Thorsgaard, N.

    2001-01-01

    Coronary angiography is the main diagnostic test for deciding whether to refer a patient for coronary revascularisation, but referral for coronary angiography may vary significantly among regions. 1 2 Regional differences have been explained by the fact that access to cardiac catheterisation faci...... facilities is associated with a higher likelihood of undergoing angiography. 3 4 We investigated the impact of exercise stress testing on decisions taken about patients suspected of having angina pectoris and the barriers to referral for coronary angiography....

  7. Psychometric testing of the Family-Carer Diabetes Management Self-Efficacy Scale.

    Science.gov (United States)

    Wichit, Nutchanath; Mnatzaganian, George; Courtney, Mary; Schulz, Paula; Johnson, Maree

    2017-11-06

    The aim of this study was to develop and test the construct and content validity, internal consistency of the Family-Carer Diabetes Management Self-Efficacy Scale (F-DMSES). A sample of 70 Thai individuals who cared for those living with type 2 diabetes mellitus (T2DM) in a rural community in Thailand was included in the study. Data were collected by a questionnaire survey in January 2014. The F-DMSES was initially derived from the DMSES, with subsequent forward and backward translations from and to English and Thai languages. The psychometric properties (content, construct and internal consistency) of the Thai version were explored using the Content Validity Index approach, exploratory factor analysis and Cronbach's alpha test. The F-DMSES initially designed with 20 items was reduced to 14 items within four factors (general diet and blood glucose monitoring, medications and complications, diet in differing situations, and weight control and physical activities), and explained 72.2% of the total variance in overarching construct. Internal consistency was supported (α = 0.89). The F-DMSES was also able to measure change over time following an intervention, with an effect size of 0.9. The F-DMSES is a valid and reliable self-administered instrument that measures the diabetes management self-efficacy of family-carers of individuals with T2DM. This instrument can be used in practice and clinical trials to assess the impact of family-carers on the health outcomes of individuals with T2DM. © 2017 John Wiley & Sons Ltd.

  8. Current issues with acetaminophen hepatotoxicity–a clinically relevant model to test the efficacy of natural products

    Science.gov (United States)

    Jaeschke, Hartmut; McGill, Mitchell R.; Williams, C. David; Ramachandran, Anup

    2011-01-01

    There is a significant need to evaluate the therapeutic potential of natural products and other compounds purported to be hepatoprotective. Acetaminophen-induced liver injury, especially in mice, is an attractive and widely used model for this purpose because it is both clinically relevant and experimentally convenient. However, the pathophysiology of liver injury after acetaminophen overdose is complex. This review describes the multiple steps and signaling pathways involved in acetaminophen-mediated cell death. The toxicity is initiated by formation of a reactive metabolite, which depletes glutathione and binds to cellular proteins, especially in mitochondria. The resulting mitochondrial oxidant stress and peroxynitrite formation, in part through amplification by c-jun-N-terminal kinase activation, leads to mitochondrial DNA damage and opening of the mitochondrial permeability transition pore. Endonucleases from the mitochondrial intermembrane space and lysosomes are responsible for nuclear DNA fragmentation. Despite the oxidant stress, lipid peroxidation is not a relevant mechanism of injury. The mitochondrial dysfunction and nuclear DNA damage ultimately cause oncotic necrotic cell death with release of damage-associated molecular patterns that trigger a sterile inflammatory response. Current evidence supports the hypothesis that innate immune cells do not contribute to injury but are involved in cell debris removal and regeneration. This review discusses the latest mechanistic aspects of acetaminophen hepatotoxicity and demonstrates ways to assess the mechanisms of drug action and design experiments needed to avoid pitfalls and incorrect conclusions. This review should assist investigators in the optimal use of this model to test the efficacy of natural compounds and obtain reliable mechanistic information. PMID:21296090

  9. 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

  10. Anticoccidial efficacy testing: In vitro Eimeria tenella assays as replacement for animal experiments.

    Science.gov (United States)

    Thabet, Ahmed; Zhang, Runhui; Alnassan, Alaa-Aldin; Daugschies, Arwid; Bangoura, Berit

    2017-01-15

    Availability of an accurate in vitro assay is a crucial demand to determine sensitivity of Eimeria spp. field strains toward anticoccidials routinely. In this study we tested in vitro models of Eimeria tenella using various polyether ionophores (monensin, salinomycin, maduramicin, and lasalocid) and toltrazuril. Minimum inhibitory concentrations (MIC 95 , MIC 50/95 ) for the tested anticoccidials were defined based on a susceptible reference (Houghton strain), Ref-1. In vitro sporozoite invasion inhibition assay (SIA) and reproduction inhibition assay (RIA) were applied on sensitive laboratory (Ref-1 and Ref-2) and field (FS-1, FS-2, and FS-3) strains to calculate percent of inhibition under exposure of these strains to the various anticoccidials (%I SIA and%I RIA, respectively). The in vitro data were related to oocyst excretion, lesion scores, performance, and global resistance indices (GI) assessed in experimentally infected chickens. Polyether ionophores applied in the RIA were highly effective at MIC 95 against Ref-1 and Ref-2 (%I RIA ≥95%). In contrast, all tested field strains displayed reduced to low efficacy (%I RIA animal model (p89%) against all strains used in this study. However, adjusted GI (GI adj ) for toltrazuril-treated groups exhibited differences between reference and field strains which might indicate varying sensitivity. RIA is a suitable in vitro tool to detect sensitivity of E. tenella towards polyether ionophores, and may thus help to reduce, replace, or refine use of animal experimentation for in vivo sensitivity assays. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Safety and Efficacy Assessment of Two New Leprosy Skin Test Antigens: Randomized Double Blind Clinical Study

    Science.gov (United States)

    Rivoire, Becky L.; Groathouse, Nathan A.; TerLouw, Stephen; Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Khadge, Saraswoti; Kunwar, Chatra B.; Macdonald, Murdo; Hawksworth, Rachel; Thapa, Min B.; Hagge, Deanna A.; Tibbals, Melinda; Smith, Carol; Dube, Tina; She, Dewei; Wolff, Mark; Zhou, Eric; Makhene, Mamodikoe; Mason, Robin; Sizemore, Christine; Brennan, Patrick J.

    2014-01-01

    Background New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. Methods A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 µg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 µg (high dose) and 0.1 µg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. Findings In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens

  12. Safety and efficacy assessment of two new leprosy skin test antigens: randomized double blind clinical study.

    Directory of Open Access Journals (Sweden)

    Becky L Rivoire

    Full Text Available New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials.A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.. Healthy non-exposed subjects (n = 10 received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg of MLSA-LAM (n = 5 or MLCwA (n = 5 and control antigens [Rees MLSA (1.0 µg and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal, but involved only the 1.0 µg (high dose and 0.1 µg (low dose of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose, each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT leprosy patients, 20 household contacts of leprosy patients (HC, and 20 tuberculosis (TB patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration.In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50 showed induration against the high dose of each antigen, and 4% (2 of 50 reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60

  13. Safety and efficacy assessment of two new leprosy skin test antigens: randomized double blind clinical study.

    Science.gov (United States)

    Rivoire, Becky L; Groathouse, Nathan A; TerLouw, Stephen; Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Khadge, Saraswoti; Kunwar, Chhatra B; Kunwar, Chatra B; Macdonald, Murdo; Hawksworth, Rachel; Thapa, Min B; Hagge, Deanna A; Tibbals, Melinda; Smith, Carol; Dube, Tina; She, Dewei; Wolff, Mark; Zhou, Eric; Makhene, Mamodikoe; Mason, Robin; Sizemore, Christine; Brennan, Patrick J

    2014-01-01

    New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 µg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 µg (high dose) and 0.1 µg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60

  14. Genetic susceptibility to Gilbert's syndrome in a valencian population; efficacy of the fasting test.

    Science.gov (United States)

    Torres, A K; Escartín, N; Monzó, C; Guzmán, C; Ferrer, I; González-Muñoz, C; Peña, P; Monzó, V; Marcaida, G; Rodríguez-López, R

    To describe the populational distribution of the UGT1A1*28 variant (genetic variant code rs8175347) located in the promotor of the UGT gene and correlate its genotypes with the results of the fasting test, as well as its relationship with the biochemical disorder of Gilbert's syndrome (GS) in a Valencian population. We studied the prevalence of the genotypes (TA) 6/6 (TA) 6/7 and (TA) 7/7 of the deleterious variant rs8175347 in 144 patients with hyperbilirubinemia, 38 of whom had previously undergone the fasting test to diagnose GS, and in 150 control patients. By analysing the genomic region of the TATA box of the UGT1A1 gene promotor using Sanger sequencing, we established the correlation between the rs8175347 genotypes and the fasting test results and with the patients' biochemical disorders. The rate of heterozygosity of allele (TA) 7 in the control population was 32% and increased to 87.59% among the patients with suspected GS. The rate of genotype TA 7/7 was 81.94% among the patients with hyperbilirubinemia, compared with 11.33% in the control patients. The fasting test showed a 15.79% rate of false negatives and a 5.26% rate of false positives. The high frequency of allele (TA) 7 among the Valencian control population, almost double the 5% reported for European control patients, confirms the high rate of GS reported in the Spanish population, without observing significant differences between the geographical ends of the country. The efficacy and reliability of the fasting test for the diagnosis of GS is questionable. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  15. Therapeutic efficacy of bone marrow derived mesenchymal stromal cells versus losartan on adriamycin-induced renal cortical injury in adult albino rats.

    Science.gov (United States)

    Anan, Hoda H; Zidan, Rania A; Shaheen, Mohammad A; Abd-El Fattah, Enas A

    2016-08-01

    Renal disease is a major health problem. Recent studies have reported the efficacy of stem cell therapy in nephropathy animal models. This study was designed to investigate the therapeutic effectiveness of bone marrow-derived mesenchymal stromal cells (MSCs) versus losartan in the treatment of renal alterations induced by adriamycin (ADR). Thirty-five adult male albino rats were divided into four groups. Group I was the control group. Group II (adriamycin-treated group),which included ten rats that were injected with a single dose of adriamycin (15 mg/kg) intraperitoneally, was subdivided into subgroup IIa and IIb and they were sacrificed 1 week and 5 weeks after adriamycin injection, respectively. Group III was the adriamycin + losartan-treated group and 1 week after adriamycin injection five rats received 10 mg/kg of losartan orally and daily for 4 weeks. Group IV was the adriamycin + MSC-treated group); five rats were injected with adriamycin as group II then supplied with MSCs at a dose of 1 × 10(6) cells suspended in 0.5 mL of phosphate-buffered saline (PBS) per rat in the tail vein 1 week after adriamycin injection. Rats of this group were sacrificed 4 weeks after the stem cell injection. Blood urea nitrogen and serum creatinine were measured. Samples from renal cortex were processed for light and electron microscope examination. As regards light microscope, sections were stained with hematoxylin and eosin (H-E), periodic acid-Schiff (PAS), masson trichrome, proliferating cell nuclear antigen (PCNA) and Caspase-3 immunohistochemical stains. Morphometrical and statistical analyses were also conducted. Examination of adriamycin-treated group revealed deterioration of renal functions and various degrees of renal structural alterations as vacuolated cytoplasm, dark nuclei and detached epithelial lining. Administration of losartan partially improved ADR-induced kidney dysfunction, whereas MSCs denoted a more ameliorative role evidenced by

  16. Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer.

    Science.gov (United States)

    Nilsson, Martin P; Winter, Christof; Kristoffersson, Ulf; Rehn, Martin; Larsson, Christer; Saal, Lao H; Loman, Niklas

    2017-04-01

    Increasing evidence supports the benefit of identifying BRCA1 and BRCA2 germline mutations in early breast cancer. Selection of patients for genetic testing is based on defined criteria taking individual and family history related factors into account. It is important to make a distinction between efficacy and effectiveness of BRCA testing criteria. Efficacy can be defined as the performance under ideal circumstances, whereas effectiveness refers to its real life performance. To allow for an unbiased and detailed evaluation of efficacy and effectiveness of the Swedish BRCA testing criteria, we retrospectively analyzed a prospectively collected cohort of 273 breast cancer patients from the well-characterized, population-based, single-site All Breast Cancer in Malmö (ABiM) study. The patients were diagnosed with breast cancer during the years 2007 through 2009. Out of 20 mutation carriers identified, 13 fulfilled Swedish criteria at time of diagnosis. Thus, the efficacy of these criteria was 65%. Excluding three patients in whom a mutation was already known at time of diagnosis, only 3/17 had been identified in the clinical routine, corresponding to an effectiveness of 18%. Here we detail the reasons why mutation carriers in our cohort were not detected though routine health care. In conclusion, effectiveness of BRCA testing criteria was much lower than efficacy. Our results indicate that current testing criteria and procedures associated with BRCA1 and BRCA2 testing are insufficient. There is room for improvement of their efficacy, but even more so regarding effectiveness. Clinical BRCA testing routines need to be critically revised.

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

    Directory of Open Access Journals (Sweden)

    Marta Koper

    2015-06-01

    Full Text Available 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, performed during the antenatal visit. On the basis of patients' history, physical examination and STS results, early latent syphilis was diagnosed in the first patient; biological false positive reactions were considered in the second one. Both patients received procaine penicillin treatment. Conclusions. Screening for syphilis in pregnancy as a part of antenatal care and appropriate treatment with penicillin are the most effective interventions to prevent complications of syphilis in pregnancy. It is also important to adapt modern European Guidelines for management of syphilis to Polish conditions.

  18. Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with {sup 211}At-MX35 F(ab'){sub 2}: therapeutic efficacy and myelotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Elgqvist, Joergen [Department of Radiation Physics, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden)]. E-mail: jorgen.elgqvist@radfys.gu.se; Andersson, Hakan [Department of Oncology, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Baeck, Tom [Department of Radiation Physics, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Claesson, Ingela [Department of Oncology, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Hultborn, Ragnar [Department of Oncology, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Jensen, Holger [PET and Cyclotron Unit, Rigshospitalet, 2100 Copenhagen (Denmark); Lindegren, Sture [Department of Radiation Physics, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Olsson, Marita [Bioinformatics Core Facility, Goeteborg University and Department of Mathematical Statistics, Chalmers University of Technology, SE-412 96 Goeteborg (Sweden); Palm, Stig [Department of Radiation Physics, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Warnhammar, Elisabet [Department of Oncology, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden); Jacobsson, Lars [Department of Radiation Physics, Sahlgrenska Academy at Goeteborg University, SE-413 45 Goeteborg (Sweden)

    2006-11-15

    Objective: The aim of this study was to investigate the therapeutic efficacy and myelotoxicity during fractionated radioimmunotherapy of ovarian cancer in mice. The study was performed using the monoclonal antibody MX35 F(ab'){sub 2} labeled with the {alpha}-particle emitter {sup 211}At. Methods: Animals were intraperitoneally inoculated with {approx}1x10{sup 7} cells of the cell line NIH:OVCAR-3. Four weeks later, the mice were given the first treatment. Six groups of animals were intraperitoneally injected with {approx}800, 3x {approx}267, {approx}400, 3x {approx}133, {approx}50 or 3x {approx}17 kBq {sup 211}At-MX35 F(ab'){sub 2} (n=18 in each group). The second and third injections for Groups 2, 4 and 6 were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with unlabeled MX35 F(ab'){sub 2} (n=12). Eight weeks after the last injection, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Blood counts were determined for each mouse in Groups 1 and 2 before the first injection and 3, 7, 11, 15 and 23 days after the first injection. The calculation of the mean absorbed dose to the bone marrow was based on the ratio between the {sup 211}At-activity concentration in bone and blood [i.e., the bone-to-blood ratio (BBLR)] as well as that between the {sup 211}At-activity concentration in bone marrow and blood [i.e., the bone-marrow-to-blood ratio (BMBLR)] and the cumulated activity and absorbed fraction of the {alpha}-particles emitted by {sup 211}At in the bone marrow. Results: The tumor-free fractions of animals were 56% and 41% when treated with {approx}800 kBq and 3x {approx}267 kBq {sup 211}At-MX35 F(ab'){sub 2}, respectively; 39% and 28% when treated with {approx}400 kBq and 3x {approx}133 kBq {sup 211}At-MX35 F(ab'){sub 2}, respectively; and 17% and 22% when treated with {approx}50 kBq or 3x {approx}17 kBq {sup 211}At-MX35 F(ab'){sub 2

  19. Postprandial Reactive Hypoglycaemia: Varying Presentation Patterns on Extended Glucose Tolerance Tests and Possible Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Kevin Stuart

    2013-01-01

    Full Text Available Reactive hypoglycemia is a state characterised by sympathetic or neuroglycopenic symptoms associated with hypoglycaemia in the postprandial state resulting in considerable distress to the patient. It is our practice to carry out either extended glucose tolerance tests (eGTTs or mixed meal tests in these patients. We describe two patients who experienced hypoglycaemic symptoms early and late during eGTT. The patient who experienced symptoms early, in contrast to the patient who presented with late symptoms, did not possess any characteristics of the metabolic syndrome. Based on clinical symptoms, glucose, insulin, and free fatty acid (FFA levels, we speculate on possible mechanisms that may have accounted for each of their presentation patterns. We then discuss low glycaemic index diet which will be the mainstay of management.

  20. Genetic Tests To Evaluate Prognosis and Predict Therapeutic Response in Acute Myeloid Leukemia

    OpenAIRE

    Gulley, Margaret L; Shea, Thomas C.; Fedoriw, Yuri

    2010-01-01

    Management of patients with acute myeloid leukemia relies on genetic tests that inform diagnosis and prognosis, predict response to therapy, and measure minimal residual disease. The value of genetics is reinforced in the revised 2008 World Health Organization acute myeloid leukemia classification scheme. The various analytic procedures—karyotype, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, DNA sequencing, and microarray technology—each have advantages...

  1. Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform.

    Directory of Open Access Journals (Sweden)

    Jacob T Bush

    2017-09-01

    Full Text Available There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible.From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses.A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

  2. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent.

    Science.gov (United States)

    Numata, Kazushi; Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu; Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu; Karasawa, Eii; Tanaka, Katsuaki

    2010-08-01

    We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  3. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.j [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu [Department of Internal Medicine, Naruto General Hospital, 167 Naruto, Sanbu, Chiba 289-1326 (Japan); Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Karasawa, Eii [Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashi Kaigan-cho, Atami, Shizuoka 413-0012 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan)

    2010-08-15

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

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

    Science.gov (United States)

    Lv, Peijie; Liu, Jie; Yan, Xiaopeng; Chai, Yaru; Chen, Yan; Gao, Jianbo; Pan, Yuanwei; Li, Shuai; Guo, Hua; Zhou, Yue

    2017-03-01

    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 spectral imaging allows for the evaluation and early prediction of tumour response to AG-013736. • AG-013736 treatment response was evaluated by CT in a rabbit tumour model. • CT spectral imaging allows for the early treatment monitoring of targeted anti-tumour therapies. • Spectral CT findings correlated with vascular changes after anti-tumour therapies. • Spectral CT is a promising method for assessing clinical treatment response.

  5. A Novel Imaging Biomarker Extracted from Fluorescence Microscopic Imaging of TRA-8/DR5 Oligomers Predicts TRA-8 Therapeutic Efficacy in Breast and Pancreatic Cancer Mouse Models.

    Science.gov (United States)

    Kim, Harrison; Buchsbaum, Donald J; Zinn, Kurt R

    2016-06-01

    The aim of the study was to develop a reliable quantitative imaging biomarker from fluorescence microscopic imaging of TRA-8/death receptor 5 (DR5) oligomer to predict TRA-8 therapeutic efficacy in human breast and pancreatic cancer mouse models. Two breast (2LMP, SUM159) and two pancreatic (MIA PaCa-2, PANC1) cancer cell lines were used. 10(5) cells per cell line were placed in a culture dish and treated with Cy5.5-labeled TRA-8 overnight in vitro. Three fluorescence microphotographs (×20) were acquired from randomly selected areas, and about 300 cells were analyzed per cell line. Two-dimensional (2D) fluorescence signal distribution of Cy5.5-TRA-8 on each cell was measured. Gaussian curve fitting to the distribution was determined by the least square regression method, and the coefficient of determination (R (2)) of the fitting was found. In addition, two features of the best fitting Gaussian curve such as peak amplitude and the volume under the curve (VUC) were retrieved. A novel image biomarker was extracted by correlating the combination of R (2) value, peak amplitude, and the VUC with the logarithmic values of the half maximal inhibitory concentrations (IC50) of TRA-8 for the four cell lines or the percentage of tumor growth inhibition (%TGI) at a week of TRA-8 treatment in animal models. Cy5.5-TRA-8 binding to DR5 receptors resulted in an oligomer on each cell membrane, and its fluorescence signal distribution followed Gaussian curve. Peak amplitude of fluorescence signal in the oligomeric region, R (2) value of the Gaussian fitting, and the VUC in TRA-8-sensitive cells were significantly higher than those in resistant cells (p TRA-8 may serve as a predictive biomarker of TRA-8 therapy for cancer patients.

  6. Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform.

    Science.gov (United States)

    Bush, Jacob T; Wasunna, Monique; Alves, Fabiana; Alvar, Jorge; Olliaro, Piero L; Otieno, Michael; Sibley, Carol Hopkins; Strub Wourgaft, Nathalie; Guerin, Philippe J

    2017-09-01

    There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL) annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD) files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible. From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses. A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

  7. Evaluation of the short-term efficacy and safety of biological agents in different rheumatic diseases: a multidisciplinary therapeutic hospital"s experience

    Directory of Open Access Journals (Sweden)

    N A Mukhin

    2013-01-01

    Full Text Available There has been a substantial expansion in the possibilities of current therapy for rheumatic diseases (RD primarily due to the use of genetically engineered biological agents (GEBA. Objective: to evaluate the short-term efficacy and safety of GEBA in patients with different RD. Subjects and methods. The trial included all RD patients receiving GEBA: rituximab (RTM, infliximab (INF, adalimumab, etanercept, tocilizumab, abatacept in 2009-2012. Therapeutic efficiency and safety were evaluated 6 months later. The effect of GEBA was determined as “remission”, “improvement”, and “no response”, by using the parameters peculiar to specific diseases (such as BVAS, DAS28, BASDAI. Results. The trial enrolled 107 patients (49 men and 58 women; mean age 41.5 years with rheumatoid arthritis (n=34, ANCA-associated vasculitis (n = 34, systemic lupus erythematosus (n=16, cryoglobulinemic vasculitis (n=11, ankylosing spondyloarthritis (n = 8, systemic vasculitis with large artery involvement (n=6, and other RD. All the cases showed severe systemic autoimmune disease refractory to standard immunosuppressive therapy. RTM (n=66 and INF (n = 31 were most frequently used. The high rate of RTM prescription was due to the fact that this drug was given to all patients with ANCA-associated vasculitis, systemic lupus erythematosus, and cryoglobulinemic vasculitis who totaled more than half of the patients included into the trial. The vast majority of them received GEBA for the first time. After the treatment, there was remission in 62 (57.9% and improvement in 42 (39.3% cases. Mild or moderate adverse reactions were observed in 22 (20.6% patients and severe ones were seen in 6 (5.6%. Conclusion. GEBA therapy ensures a significant improvement in a substantial proportion of patients with different RD refractory to standard immunosuppressive therapy.

  8. The Recombinant Bacille Calmette–Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing

    Directory of Open Access Journals (Sweden)

    Natalie E. Nieuwenhuizen

    2017-09-01

    Full Text Available The only licensed vaccine against tuberculosis (TB, bacille Calmette–Guérin (BCG, protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes. Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔureC::hly (VPM1002 promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

  9. The design of phase II clinical trials testing cancer therapeutics: consensus recommendations from the clinical trial design task force of the national cancer institute investigational drug steering committee

    National Research Council Canada - National Science Library

    Seymour, Lesley; Ivy, S Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

    2010-01-01

    .... The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical...

  10. Efficacy Testing of H56 cDNA Tattoo Immunization against Tuberculosis in a Mouse Model.

    Science.gov (United States)

    Platteel, Anouk C M; Nieuwenhuizen, Natalie E; Domaszewska, Teresa; Schürer, Stefanie; Zedler, Ulrike; Brinkmann, Volker; Sijts, Alice J A M; Kaufmann, Stefan H E

    2017-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), remains a global threat. The only approved vaccine against TB, Mycobacterium bovis bacillus Calmette-Guérin (BCG), provides insufficient protection and, being a live vaccine, can cause disseminated disease in immunocompromised individuals. Previously, we found that intradermal cDNA tattoo immunization with cDNA of tetanus toxoid fragment C domain 1 fused to cDNA of the fusion protein H56, comprising the Mtb antigens Ag85B, ESAT-6, and Rv2660c, induced antigen-specific CD8 + T cell responses in vivo . As cDNA tattoo immunization would be safer than a live vaccine in immunocompromised patients, we tested the protective efficacy of intradermal tattoo immunization against TB with H56 cDNA, as well as with H56_E, a construct optimized for epitope processing in a mouse model. As Mtb antigens can be used in combination with BCG to boost immune responses, we also tested the protective efficacy of heterologous prime-boost, using dermal tattoo immunization with H56_E cDNA to boost BCG immunization in mice. Dermal H56 and H56_E cDNA immunization induced H56-specific CD4 + and CD8 + T cell responses and Ag85B-specific IgG antibodies, but did not reduce bacterial loads, although immunization with H56_E ameliorated lung pathology. Both subcutaneous and intradermal immunization with BCG resulted in broad cellular immune responses, with increased frequencies of CD4 + T effector memory cells, T follicular helper cells, and germinal center B cells, and resulted in reduced bacterial loads and lung pathology. Heterologous vaccination with BCG/H56_E cDNA induced increased H56-specific CD4 + and CD8 + T cell cytokine responses compared to vaccination with BCG alone, and lung pathology was significantly decreased in BCG/H56_E cDNA immunized mice compared to unvaccinated controls. However, bacterial loads were not decreased after heterologous vaccination compared to BCG alone. CD4 + T cells responding to Ag85B- and ESAT-6

  11. Evaluation of Polymerization Efficacy in Composite Resins via FT-IR Spectroscopy and Vickers Microhardness Test.

    Science.gov (United States)

    Jafarzadeh, Tahereh-Sadat; Erfan, Mohammad; Behroozibakhsh, Marjan; Fatemi, Mostafa; Masaeli, Reza; Rezaei, Yashar; Bagheri, Hossein; Erfan, Yasaman

    2015-01-01

    Background and aims. Polymerization efficacy affects the properties and performance of composite resin restorations.The purpose of this study was to evaluate the effectiveness of polymerization of two micro-hybrid, two nano-hybrid and one nano-filled ormocer-based composite resins, cured by two different light-curing systems, using Fourier transformation infrared (FT-IR) spectroscopy and Vickers microhardness testing at two different depths (top surface, 2 mm). Materials and methods. For FT-IR spectrometry, five cylindrical specimens (5mm in diameter × 2 mm in length) were prepared from each composite resin using Teflon molds and polymerized for 20 seconds. Then, 70-μm wafers were sectioned at the top surface and at2mm from the top surface. The degree of conversion for each sample was calculated using FT-IR spectroscopy. For Vickers micro-hardness testing, three cylindrical specimens were prepared from each composite resin and polymerized for 20 seconds. The Vickers microhardness test (Shimadzu, Type M, Japan) was performed at the top and bottom (depth=2 mm) surfaces of each specimen. Three-way ANOVA with independent variables and Tukey tests were performed at 95% significance level. Results. No significant differences were detected in degree of conversion and microhardness between LED and QTH light-curing units except for the ormocer-based specimen, CeramX, which exhibited significantly higher DC by LED. All the composite resins showed a significantly higher degree of conversion at the surface. Microhardness was not significantly affected by depth, except for Herculite XRV Ultra and CeramX, which showed higher values at the surface. Conclusion. Composite resins containing nano-particles generally exhibited more variations in degree of conversion and microhardness.

  12. Evaluation of Polymerization Efficacy in Composite Resins via FT-IR Spectroscopy and Vickers Microhardness Test

    Science.gov (United States)

    Jafarzadeh, Tahereh-Sadat; Erfan, Mohammad; Behroozibakhsh, Marjan; Fatemi, Mostafa; Masaeli, Reza; Rezaei, Yashar; Bagheri, Hossein; Erfan, Yasaman

    2015-01-01

    Background and aims. Polymerization efficacy affects the properties and performance of composite resin restorations.The purpose of this study was to evaluate the effectiveness of polymerization of two micro-hybrid, two nano-hybrid and one nano-filled ormocer-based composite resins, cured by two different light-curing systems, using Fourier transformation infrared (FT-IR) spectroscopy and Vickers microhardness testing at two different depths (top surface, 2 mm). Materials and methods. For FT-IR spectrometry, five cylindrical specimens (5mm in diameter × 2 mm in length) were prepared from each composite resin using Teflon molds and polymerized for 20 seconds. Then, 70-μm wafers were sectioned at the top surface and at2mm from the top surface. The degree of conversion for each sample was calculated using FT-IR spectroscopy. For Vickers micro-hardness testing, three cylindrical specimens were prepared from each composite resin and polymerized for 20 seconds. The Vickers microhardness test (Shimadzu, Type M, Japan) was performed at the top and bottom (depth=2 mm) surfaces of each specimen. Three-way ANOVA with independent variables and Tukey tests were performed at 95% significance level. Results. No significant differences were detected in degree of conversion and microhardness between LED and QTH light-curing units except for the ormocer-based specimen, CeramX, which exhibited significantly higher DC by LED. All the composite resins showed a significantly higher degree of conversion at the surface. Microhardness was not significantly affected by depth, except for Herculite XRV Ultra and CeramX, which showed higher values at the surface. Conclusion. Composite resins containing nano-particles generally exhibited more variations in degree of conversion and microhardness. PMID:26889359

  13. Evaluation of Polymerization Efficacy in Composite Resins via FT-IR Spectroscopy and Vickers Microhardness Test

    Directory of Open Access Journals (Sweden)

    Tahereh-Sadat Jafarzadeh

    2015-12-01

    Full Text Available Background and aims. Polymerization efficacy affects the properties and performance of composite resin restorations.The purpose of this study was to evaluate the effectiveness of polymerization of two micro-hybrid, two nano-hybrid and one nano-filled ormocer-based composite resins, cured by two different light-curing systems, using Fourier transformation infrared (FT-IR spectroscopy and Vickers microhardness testing at two different depths (top surface, 2 mm. Materials and methods. For FT-IR spectrometry, five cylindrical specimens (5mm in diameter × 2 mm in length were prepared from each composite resin using Teflon molds and polymerized for 20 seconds. Then, 70-μm wafers were sectioned at the top surface and at2mm from the top surface. The degree of conversion for each sample was calculated using FT-IR spectroscopy. For Vickers micro-hardness testing, three cylindrical specimens were prepared from each composite resin and polymerized for 20 seconds. The Vickers microhardness test (Shimadzu, Type M, Japan was performed at the top and bottom (depth=2 mm surfaces of each specimen. Three-way ANOVA with independent variables and Tukey tests were performed at 95% significance level. Results. No significant differences were detected in degree of conversion and microhardness between LED and QTH light-curing units except for the ormocer-based specimen, CeramX, which exhibited significantly higher DC by LED. All the composite resins showed a significantly higher degree of conversion at the surface. Microhardness was not significantly affected by depth, except for Herculite XRV Ultra and CeramX, which showed higher values at the surface. Conclusion. Composite resins containing nano-particles generally exhibited more variations in degree of conversion and microhardness.

  14. Completion of therapeutic and safety monitoring tests in Lebanese outpatients on chronic medications: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ramia E

    2014-09-01

    Full Text Available Elsy Ramia, Rony Zeenny Department of Pharmacy Practice, School of Pharmacy, Lebanese American University, Byblos, Lebanon Purpose: To evaluate the appropriateness of laboratory-test monitoring recommended for patients on chronic medication therapies in the Lebanese community setting.Patients and methods: In October 2011, all outpatients visiting selected community pharmacies in Lebanon were screened by pharmacists to evaluate their use of one or more chronic medications requiring safety and/or therapeutic laboratory tests. The list of medications was elaborated after an extensive review of laboratory-test monitoring recommendations from pertinent up-to-date clinical guidelines, medications that have been issued black box warnings for monitoring, and the most current information from the US Food and Drug Administration website. Patients receiving these medications were subjected to a questionnaire assessing the appropriateness of their laboratory-test monitoring. The study was approved by the Lebanese American University’s Institutional Review Board.Results: A total of 284 outpatients, with almost equal distribution by sex, were identified during the aforementioned period to be on one or more of the specified medications. The majority of the sample (68% was younger than 65 years of age. Overall, most of the study group (65% were found to be partially monitored with laboratory tests, while only 27% were fully monitored and 8% were not monitored at all. The study group reported clinic-visit intervals as follows: more than a year (35%, on yearly basis (18%, every 6 months (25%, every 3 months (16%, less than 3 months (6%. Conclusion: Seventy-three percent (73% of the study group were receiving incomplete therapeutic/safety laboratory-test monitoring recommended for patients on chronic medication in the Lebanese community. It is concluded from the results that patients need to better understand the importance of recommended test monitoring for the

  15. Enhancing the efficacy of the 20 m multistage shuttle run test.

    Science.gov (United States)

    Flouris, A D; Metsios, G S; Koutedakis, Y

    2005-03-01

    Maximal oxygen uptake (Vo(2max)) of 44 ml kg(-1) min(-1) is an accepted criterion (Vo(2CR)) below which health and fitness for young male adults may be compromised. New algorithms validated for Vo(2CR) screening using the 20 m multistage shuttle run test (20mMST) were developed. Vo(2max) was assessed in 110 males using a stationary gas analyser in a treadmill test (TT) and in 40 of these subjects using a portable gas analyser in the 20mMST. Vo(2max) predicted from the 20mMST in 70 subjects was used for cross validation. Two equations predicting Vo(2max) during 20mMST (EQ(MST)) and TT (EQ(TT)) were developed. Significant energy cost variance (EC(V)) was detected between TT and 20mMST (p0.05) between predicted and measured values. Prevalence of low fitness based on Vo(2CR) was 0.37. McNemar chi(2) indicated significant differences in sensitivity (p0.05), mean predicted Vo(2max) from EQ(LEG) was significantly higher compared to TT Vo(2max) (p<0.001). These algorithms increase the efficacy of 20mMST to accurately evaluate aspects of health and fitness.

  16. Challenges and limitations of testing efficacy of aerosol device delivery in young children.

    Science.gov (United States)

    Goralski, Jennifer L; Davis, Stephanie D

    2014-08-01

    An increasing number of medical conditions are chronically or acutely managed with some form of aerosolized therapy. Due to the benefit of directly administering medications to the intended site of action, there is great interest in evaluating treatments for aerosol use. One of the major challenges in selecting and testing new drug-device combinations in children is the uncertainty regarding the appropriate outcome measure to choose. In studies involving adult patients, typically exacerbations of disease or airflow obstruction are assessed as endpoints in drug trials or device assessment. However, in young children, choosing endpoints to assess efficacy is difficult due to the potential lack of sensitive, noninvasive endpoints that are easily performed across sites. In this review, we discuss the challenges and limitations of selecting clinical endpoints for drug-device trials in the youngest population, with a focus on novel emerging technologies. This article provides an overview of preschool and infant pulmonary function testing, multiple-breath washout, imaging techniques including computed tomography and magnetic resonance imaging, flexible bronchoscopy in children, mucociliary clearance scans, and exhaled breath condensate.

  17. Testing efficacy of monthly forecast application in agrometeorology: Winter wheat phenology dynamic

    Science.gov (United States)

    Lalic, B.; Jankovic, D.; Dekic, Lj; Eitzinger, J.; Firanj Sremac, A.

    2017-02-01

    Use of monthly weather forecast as input meteorological data for agrometeorological forecasting, crop modelling and plant protection can foster promising applications in agricultural production. Operational use of monthly or seasonal weather forecast can help farmers to optimize field operations (fertilizing, irrigation) and protection measures against plant diseases and pests by taking full advantage of monthly forecast information in predicting plant development, pest and disease risks and yield potentials few weeks in advance. It can help producers to obtain stable or higher yield with the same inputs and to minimise losses caused by weather. In Central and South-Eastern Europe ongoing climate change lead to shifts of crops phenology dynamics (i.e. in Serbia 4-8 weeks earlier in 2016 than in previous years) and brings this subject in the front of agronomy science and practice. Objective of this study is to test efficacy of monthly forecast in predicting phenology dynamics of different winter wheat varieties, using phenological model developed by Forecasting and Warning Service of Serbia in plant protection. For that purpose, historical monthly forecast for four months (March 1, 2005 - June 30, 2005) was assimilated from ECMWF MARS archive for 50 ensemble members and control run. Impact of different agroecological conditions is tested by using observed and forecasted data for two locations - Rimski Sancevi (Serbia) and Groß-Enzersdorf (Austria).

  18. Preoperative cellulose porous beads for therapeutic embolization of meningioma: provocation test and technical considerations

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Yutaka; Morioka, Motohiro; Yano, Shigetoshi; Nakamura, Hideo; Makino, Keishi; Mizuno, Takamasa; Takeshima, Hideo; Kuratsu, Jun-ichi [Kumamoto University, Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto (Japan); Hamada, Jun-ichiro [Kanazawa University, Department of Neurosurgery, Graduate School of Medical Sciences, Kanazawa (Japan)

    2007-05-15

    Cellulose porous beads (CPBs) are exceptionally uniform in size and nonabsorbable and they provide highly effective tumor devascularization. The risk of cranial nerve palsy must not be overlooked when embolization with CPBs is considered in meningioma patients. We attempted to identify patients at risk of cranial nerve palsy after meningioma embolization. Prior to preoperative superselective embolization with 200 {mu}m diameter CPBs, 141 patients with meningioma underwent provocation test with lidocaine and amytal. They were divided into two groups on the basis of whether they were or were not considered eligible for embolization. We evaluated the differences between the two groups with respect to tumor anatomy, angiographic findings, and clinical presentation and recorded complications associated with the embolization of the meningioma. Of the 141 patients, 128 underwent CPB embolization (group 2); 13 were not embolized because their provocation test results were positive (group 1, n = 11) or because they showed vasospasm (n = 2). Group 1 patients had meningioma in the cavernous sinus or petroclival region. Characteristically, the feeders were of middle meningeal artery origin and exhibited a posteromedial course toward the petrous apex or cavernous sinus. In group 2 patients the middle meningeal artery was the feeder, but it lacked branches coursing posteromedially. Three of these patients experienced complications which included intratumoral hemorrhage (n = 2) and post-embolization hearing disturbance (n = 1). Patients with meningioma whose tumor-feeding arteries run posteromedially toward the petrous apex or cavernous sinus are at increased risk of post-embolization cranial nerve palsy. Appropriate protocols, including lidocaine and amytal provocation tests, may reduce the risk of complications after CPB embolization of the external carotid territory in this group of patients. (orig.)

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

    Science.gov (United States)

    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.

  20. A Technology Platform to Test the Efficacy of Purification of Alginate

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  4. Testing the Efficacy of a Computer-Based Parent-Adolescent Sexual Communication Intervention for Latino Parents

    Science.gov (United States)

    Villarruel, Antonia M.; Loveland-Cherry, Carol J.; Ronis, David L.

    2010-01-01

    The efficacy of a computer-based intervention to increase parent-adolescent communication among Latino parents and adolescents was tested in a randomized controlled trial. Parents assigned to receive the 2-session intervention reported greater general communication, sexual communication, and comfort with communication at 3-month follow-up than did…

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  7. A Confirmatory Test of the Factor Structure of the Short Form of the Career Decision Self-Efficacy Scale

    Science.gov (United States)

    Miller, Matthew J.; Roy, Kerrin Sendrowitz; Brown, Steven D.; Thomas, James; McDaniel, Cyndi

    2009-01-01

    The present study tested a number of theoretically and empirically derived measurement models of the Career Decision Self-Efficacy Scale-Short Form (CDSES-SF) using confirmatory factor analysis. Betz's five-factor model of the CDSES-SF, along with a number of alternative models, demonstrated adequate model fit in two independent samples. Based on…

  8. The Effect of the Attachment Styles and Self-Efficacy of Adolescents Preparing for University Entrance Tests in Turkey on Predicting Test Anxiety

    Science.gov (United States)

    Erzen, Evren; Odaci, Hatice

    2016-01-01

    The purpose of this study was to determine the effect of attachment styles and self-efficacy of adolescents preparing for university entrance exams in Turkey on predicting test anxieties. The study group consisted of 884 final-year high school students (423 female and 461 male) attending different types of high school, preparing for university…

  9. Efficacy of conservative treatment regimes for hip osteoarthritis - Evaluation of the therapeutic exercise regime "Hip School": A protocol for a randomised, controlled trial

    Directory of Open Access Journals (Sweden)

    Krauss Inga

    2011-11-01

    Full Text Available Abstract Background Hip osteoarthritis (hip OA is a disease with a major impact on both national economy and the patients themselves. Patients suffer from pain and functional impairment in activities of daily life which are associated with a decrease in quality of life. Conservative therapeutic interventions such as physical exercises aim at reducing pain and increasing function and health-related quality of life. However, there is only silver level evidence for efficacy of land-based physical exercise in the treatment of hip OA. The purpose of this randomized controlled trial is to determine whether the specific 12-week exercise regime "Hip School" can decrease bodily pain and improve physical function and life quality in subjects with hip osteoarthritis. Methods/Design 217 participants with hip OA, confirmed using the clinical score of the American College of Rheumatology, are recruited from the community and randomly allocated to one of the following groups: (1 exercise regime "Hip School", n = 70; (2 Non-intervention control group, n = 70; (3 "Sham" ultrasound group, n = 70; (4 Ultrasound group, n = 7. The exercise regime combines group exercises (1/week, 60-90' and home-based exercises (2/week, 30-40'. Sham ultrasound and ultrasound are given once a week, 15'. Measures are taken directly prior to (M1 and after (M2 the 12-week intervention period. Two follow-ups are conducted by phone 16 and 40 weeks after the intervention period. The primary outcome measure is the change in the subscale bodily pain of the SF36 from M1 to M2. Secondary outcomes comprise the WOMAC score, SF36, isometric strength of hip muscles, spatial-temporal and discrete measures derived from clinical gait analysis, and the length of the centre of force path in different standing tasks. An intension-to-treat analysis will be performed using multivariate statistics (group × time. Discussion Results from this trial will contribute to the evidence regarding the effect of a

  10. Selective dorsal rhizotomy for the treatment of severe spastic cerebral palsy: efficacy and therapeutic durability in GMFCS grade IV and V children.

    Science.gov (United States)

    D'Aquino, Daniel; Moussa, Ahmad A; Ammar, Amr; Ingale, Harshal; Vloeberghs, Michael

    2017-11-07

    Selective dorsal rhizotomy (SDR) has been established as an effective surgical treatment for spastic diplegia. The applicability of SDR to the full spectrum of spastic cerebral palsy and the durability of its therapeutic effects remain under investigation. There are currently limited data in the literature regarding efficacy and outcomes following SDR in Gross Motor Function Classification System (GMFCS) IV and V patients. Intrathecal baclofen has traditionally been the surgical treatment of choice for these patients. When utilised primarily as a treatment for the relief of spasticity, it is proposed that SDR represents a rational and effective treatment option for this patient group. We report our outcomes of SDR performed on children with severe cerebral palsy (GMFCS grade IV and V). The commensurate improvement in upper as well as lower limb spasticity is highlighted. Apparent benefit to urological function following SDR in this patient group is also discussed. A retrospective review of prospectively collected data for 54 paediatric patients with severe cerebral palsy (GMFCS IV-V) who received SDR plus specialised physiotherapy. Mean age was 10.2 years (range, 3.0-19.5). SDR guided by electrophysiological monitoring was performed by a single experienced neurosurgeon. All subjects received equivalent physiotherapy. The primary outcome measure was change to the degree of spasticity following SDR. Spasticity of upper and lower limb muscle groups were quantified and standardised using the Ashworth score. Measures were collected at baseline and at 2-, 8- and 14-month postoperative intervals. In addition, baseline and 6-month postoperative urological function was also evaluated as a secondary outcome measure. The mean lower limb Ashworth score at baseline was 3.2 (range, 0-4). Following SDR, significant reduction in lower limb spasticity scores was observed at 2 months and maintained at 8 and 14 months postoperatively (Wilcoxon rank, p V patients. Urological

  11. Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles.

    Science.gov (United States)

    Warsame, Marian; Hassan, Abdillahi Mohamed; Barrette, Amy; Jibril, Ali Mohamed; Elmi, Husein Haji; Arale, Abdulkadir Mohamed; Mohammady, Hanan El; Nada, Rania A; Amran, Jamal Ghilan Hefzullah; Muse, Abdikarim; Yusuf, Fahmi Essa; Omar, Abdiqani Sheikh

    2015-04-01

    Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first-line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011. Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) genes. The proportion of PCR-corrected treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR = 5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96). The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy. © 2015 John Wiley & Sons Ltd.

  12. Effects of three therapeutic doses of codeine/paracetamol on driving performance, a psychomotor vigilance test, and subjective feelings.

    Science.gov (United States)

    Amato, Jean-Noël; Marie, Sullivan; Lelong-Boulouard, Véronique; Paillet-Loilier, Magalie; Berthelon, Catherine; Coquerel, Antoine; Denise, Pierre; Bocca, Marie-Laure

    2013-07-01

    Some recent pharmacoepidemiological studies revealed an elevated risk of driving accidents after opioid analgesics uses. Among analgesics, codeine is often associated with paracetamol in numerous pharmaceutical specialties. The objective of this study was to evaluate the dose-effect relationship of three usual therapeutic doses of codeine/paracetamol on driving ability, psychomotor performance, subjective alertness, in link with blood concentrations in healthy young volunteers. Driving performance, responses to psychomotor vigilance tests, and scales reflecting alertness were evaluated during the morning after drug intake in a double-blind, randomized, placebo-controlled study. Sixteen healthy volunteers (23.4 ± 2.7 years old, 8 men and 8 women) participated in this balanced, cross-over study. Three doses of codeine/paracetamol (20/400, 40/800, 60/1200 mg) were evaluated against placebo. Two blood samples were collected, 1 and 4 h after drug intake. In serum, codeine and morphine concentrations were determined in serum using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry, and paracetamol concentrations using fluorescence polarization immunoassay. Driving and psychomotor performance were not affected by any of the three codeine/paracetamol doses. However, significant, though modest, correlations were observed between the driving parameters and both morphine and codeine blood concentrations. This study did not reveal any significant impairment in performance due to the three therapeutic doses used in healthy young volunteers. However, the relationships between drug blood concentration and behavioral measures suggest that an inter-subject variability in blood concentration may influence the power of the observed drug effect.

  13. An Investigation of the Effects of Reciprocal Peer Tutoring on Achievement, Self-Efficacy, and Test Anxiety.

    Science.gov (United States)

    Griffin; Griffin

    1998-07-01

    Reciprocal peer tutoring (RPT) is a cooperative learning strategy which capitalizes on the benefit students receive from preparing to tutor one another. In these experiments we investigated the effects of RPT on the academic achievement, academic self-efficacy, and test anxiety of undergraduate students. Undergraduate education majors enrolled in either human growth and development or educational psychology participated in the study. Students developed a series of test questions, used these questions to quiz each other prior to unit examinations, and provided corrective feedback to the questions. Statistically significant findings were inconsistent across the experiments. In short, RPT appears to have, at best, inconsistent effects on achievement, test anxiety, and academic self-efficacy. Copyright 1998 Academic Press.

  14. Testing the Efficacy of DNA Barcodes for Identifying the Vascular Plants of Canada

    Science.gov (United States)

    Kuzmina, Maria L.; Sills, Jesse; Zakharov, Evgeny V.; Hebert, Paul D. N.

    2017-01-01

    Their relatively slow rates of molecular evolution, as well as frequent exposure to hybridization and introgression, often make it difficult to discriminate species of vascular plants with the standard barcode markers (rbcL, matK, ITS2). Previous studies have examined these constraints in narrow geographic or taxonomic contexts, but the present investigation expands analysis to consider the performance of these gene regions in discriminating the species in local floras at sites across Canada. To test identification success, we employed a DNA barcode reference library with sequence records for 96% of the 5108 vascular plant species known from Canada, but coverage varied from 94% for rbcL to 60% for ITS2 and 39% for matK. Using plant lists from 27 national parks and one scientific reserve, we tested the efficacy of DNA barcodes in identifying the plants in simulated species assemblages from six biogeographic regions of Canada using BLAST and mothur. Mean pairwise distance (MPD) and mean nearest taxon distance (MNTD) were strong predictors of barcode performance for different plant families and genera, and both metrics supported ITS2 as possessing the highest genetic diversity. All three genes performed strongly in assigning the taxa present in local floras to the correct genus with values ranging from 91% for rbcL to 97% for ITS2 and 98% for matK. However, matK delivered the highest species discrimination (~81%) followed by ITS2 (~72%) and rbcL (~44%). Despite the low number of plant taxa in the Canadian Arctic, DNA barcodes had the least success in discriminating species from this biogeographic region with resolution ranging from 36% with rbcL to 69% with matK. Species resolution was higher in the other settings, peaking in the Woodland region at 52% for rbcL and 87% for matK. Our results indicate that DNA barcoding is very effective in identifying Canadian plants to a genus, and that it performs well in discriminating species in regions where floristic diversity is

  15. Efficacy of Modafinil in 10 Taiwanese Patients With Narcolepsy: Findings Using the Multiple Sleep Latency Test and Epworth Sleepiness Scale

    Directory of Open Access Journals (Sweden)

    Shih-Bin Yeh

    2010-08-01

    Full Text Available This is the first report describing the efficacy of modafinil therapy for narcolepsy in patients in Taiwan. The purpose of this study was to compare the objective Multiple Sleep Latency Test (MSLT and the subjective Epworth Sleepiness Scale (ESS for evaluating the efficacy of modafinil in treating excessive daytime sleepiness in patients with narcolepsy in Taiwan. Ten consecutive patients with narcolepsy-with-cataplexy who were treated with 200 mg/day modafinil for more than 6 months at our sleep center between January 2003 and December 2007 were included in this study. This comparative study was prompted by the requirement of the Bureau of National Health Insurance in Taiwan that modafinil users need to be followed up with MSLTs every 6–12 months. The mean age at onset of narcolepsy onset in these 10 patients was 11.8 ± 3.3 years, and eight (80% were male. We compared the differences in MSLT and ESS between baseline and follow-up at 6–12 months after starting modafinil therapy using paired t tests. ESS scores (p < 0.001 were considerably more sensitive than MSLT scores (p < 0.05 in documenting efficacy of modafinil and that the improvements in MSLT scores were minimal and remained in the pathologically sleepy range. These findings suggest that the ESS is a more sensitive and clinically meaningful tool to evaluate the efficacy of modafinil in narcolepsy.

  16. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-06-15

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

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

    Science.gov (United States)

    Kambalapally, Swetha Reddy

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

  18. Beta lactam antibiotics residues in cow's milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina.

    Science.gov (United States)

    Fejzic, Nihad; Begagic, Muris; Šerić-Haračić, Sabina; Smajlovic, Muhamed

    2014-08-27

    Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis.  Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow's milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test and Inhibition MRL test. Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level - MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues.

  19. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria

    Science.gov (United States)

    Sun, Wei; Weingarten, Rebecca A; Xu, Miao; Southall, Noel; Dai, Sheng; Shinn, Paul; Sanderson, Philip E; Williamson, Peter R; Frank, Karen M; Zheng, Wei

    2016-01-01

    Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin–auranofin–ceftazidime and colistin–auranofin–rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin–colistin–imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms. PMID:27826141

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

    Directory of Open Access Journals (Sweden)

    Boris Urban

    2008-11-01

    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.

  1. Testing the Efficacy of Theoretically Derived Improvements in the Treatment of Social Phobia

    Science.gov (United States)

    Rapee, Ronald M.; Gaston, Jonathan E.; Abbott, Maree J.

    2009-01-01

    Recent theoretical models of social phobia suggest that targeting several specific cognitive factors in treatment should enhance treatment efficacy over that of more traditional skills-based treatment programs. In the current study, 195 people with social phobia were randomly allocated to 1 of 3 treatments: standard cognitive restructuring plus in…

  2. Human vs. Computer Diagnosis of Students' Natural Selection Knowledge: Testing the Efficacy of Text Analytic Software

    Science.gov (United States)

    Nehm, Ross H.; Haertig, Hendrik

    2012-01-01

    Our study examines the efficacy of Computer Assisted Scoring (CAS) of open-response text relative to expert human scoring within the complex domain of evolutionary biology. Specifically, we explored whether CAS can diagnose the explanatory elements (or Key Concepts) that comprise undergraduate students' explanatory models of natural selection with…

  3. Testing the Immediate and Long-Term Efficacy of a Tier 2 Kindergarten Mathematics Intervention

    Science.gov (United States)

    Clarke, Ben; Doabler, Christian T.; Smolkowski, Keith; Kurtz-Nelson, Evangeline; Fien, Hank; Baker, Scott K.; Kosty, Derek

    2016-01-01

    This study examined the efficacy of a kindergarten mathematics intervention program, ROOTS, focused on developing whole-number understanding in the areas of counting and cardinality and operations and algebraic thinking for students at risk in mathematics. The study utilized a randomized block design with students within classrooms randomly…

  4. The conceptual imperfection of aquatic risk assessment tests: highlighting the need for tests designed to detect therapeutic effects of pharmaceutical contaminants

    National Research Council Canada - National Science Library

    Klaminder, Jonatan; Jonsson, Micael; Fick, Jerker; Sundelin, Anna; Brodin, Tomas

    2014-01-01

    .... This methodological bias, generated from assays where mortality in the control group is systematically disregarded, makes it difficult to measure therapeutic effects of pharmaceutical contaminants...

  5. Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments.

    Science.gov (United States)

    Sowunmi, Akintunde; Akano, Kazeem; Ntadom, Godwin; Ayede, Adejumoke I; Ibironke, Folasade O; Aderoyeje, Temitope; Adewoye, Elsie O; Fatunmbi, Bayo; Oguche, Stephen; Okafor, Henrietta U; Watila, Ismaila; Meremikwu, Martin; Agomo, Philip; Ogala, William; Agomo, Chimere; Folarin, Onikepe A; Gbotosho, Grace O; Happi, Christian T

    2017-02-07

    Artemisinin-based combination treatments (ACTs) are the first-line treatments of uncomplicated Plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children. Therapeutic efficacy of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine was evaluated in 437 anaemic and 909 non-anaemic malarious children following treatment during a seven-year period (2008-2014). Patterns of temporal changes in haematocrit were classified based on haematocrit values Fall in haematocrit/1 000 asexual parasites cleared from peripheral blood was significantly greater at lower compared to higher parasitaemias (P line treatments. These ACTs may also conserve haematocrit at high parasitaemias and in anaemic children. Pan African Clinical Trial Registry PACTR201508001188143 , 3 July 2015; PACTR201510001189370 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015.

  6. Comparative testing of disinfectant efficacy on planktonic bacteria and bacterial biofilms using a new assay based on kinetic analysis of metabolic activity.

    Science.gov (United States)

    Günther, F; Scherrer, M; Kaiser, S J; DeRosa, A; Mutters, N T

    2017-03-01

    The aim of our study was to develop a new reproducible method for disinfectant efficacy testing on bacterial biofilms and to evaluate the efficacy of different disinfectants against biofilms. Clinical multidrug-resistant strains were chosen as test isolates to ensure practical relevance. We compared the standard qualitative suspension assay for disinfectant testing, which does not take into account biofilm formation, to the new biofilm viability assay that uses kinetic analysis of metabolic activity in biofilms after disinfectant exposure to evaluate disinfectant efficacy. In addition, the efficacy of four standard disinfectants to clinical isolates was tested using both methods. All tested disinfectants were effective against test isolates when in planktonic state using the standard qualitative suspension assay, while disinfectants were only weakly effective against bacteria in biofilms. Disinfectant efficacy testing on planktonic organisms ignores biofilms and overestimates disinfectant susceptibility of bacteria. However, biofilm forming, e.g. on medical devices or hospital surfaces, is the natural state of bacterial living and needs to be considered in disinfectant testing. Although bacterial biofilms are the predominant manner of bacterial colonization, most standard procedures for antimicrobial susceptibility testing and efficacy testing of disinfectants are adapted for application to planktonic bacteria. To our knowledge, this is the first study to use a newly developed microplate-based biofilm test system that uses kinetic analysis of the metabolic activity in biofilms, after disinfectant exposure, to evaluate disinfectant efficacy. Our study shows that findings obtained from disinfectant efficacy testing on planktonic bacteria cannot be extrapolated to predict disinfectant efficacy on bacterial biofilms of clinically relevant multidrug-resistant organisms. © 2016 The Society for Applied Microbiology.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Bacterial pili, with emphasis on Mycobacterium tuberculosis curli pili: potential biomarkers for point-of care tests and therapeutics.

    Science.gov (United States)

    Naidoo, Natasha; Pillay, Manormoney

    2017-03-01

    Novel biomarkers are essential for developing rapid diagnostics and therapeutic interventions Objective: This review aimed to highlight biomarker characterisation and assessment of unique bacterial pili. A PubMed search for bacterial pili, diagnostics, vaccine and therapeutics was performed, with emphasis on the well characterised pili. In total, 46 papers were identified and reviewed. Extensive analyses of pili enabled by advanced nanotechnology and whole genome sequencing provide evidence that they are strong biomarker candidates. Mycobacterium tuberculosis curli pili are emphasised as important epitopes for the development of much needed point-of-care diagnostics and therapeutics.

  9. Therapeutic Efficacy of pH-Dependent Release Formulation of Mesalazine on Active Ulcerative Colitis Resistant to Time-Dependent Release Formulation: Analysis of Fecal Calprotectin Concentration

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    Kousaku Kawashima

    2014-01-01

    Full Text Available Purpose. Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA with a time-dependent release formulation (time-5-ASA. We examined whether pH-5-ASA is effective for active ulcerative colitis (UC in patients resistant to time-5-ASA. Methods. We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH was evaluated in a prospective manner by measuring fecal calprotectin concentration. Results. Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (n=14, administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. Conclusions. Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission.

  10. COMPARATIVE STUDY ON EFFICACY OF ROSE BENGAL PLATE TEST (I{BPT AND SERUM AGGLUTINATION TEST (SAT FOR DETECTING THE INCIDENE OF BRUCELLOSIS IN BUFFALOES (Bubolus bubolis

    Directory of Open Access Journals (Sweden)

    Idrees Ali Zahid, Ishtiaq Ahmad and Umer Hayat

    2002-03-01

    Full Text Available Rose Bengal Plate Test (RBPT and Serum Agglutination Test (SAT were applied for the diagnosis of brucellosis in 240 buffaloes maintained at organized livestock farms in Punjab, to measure their comparative efficacy. Based on RBPT and SAT, 11.25 (n=27 and 10.42 percent (n=25 buffaloes were found seropositive, 11.67 (n 28 and 4.58 percent (n= 11 animals showed doubtful results, while 77.08 (n= 185 and 85 percept (n= 204 animals were found seronegative, respectively. Rose Bengal Plate Test detected higher percentages of seropositive, doubtful and seronegative cases than those detected by Serum Agglutination Test, which showed lower percentages or seropositive, doubtful and seronegative cases. This study indicated that SAT is more sensitive and reliable diagnostic test for the detection of Brucella aborlus, antibodies in buffaloes.

  11. Survey of the therapeutic approach and efficacy of pentosan polysulfate for the prevention and treatment of equine osteoarthritis in veterinary practice in Australia.

    Science.gov (United States)

    Kramer, C M; Tsang, A S; Koenig, T; Jeffcott, L B; Dart, C M; Dart, A J

    2014-12-01

    To survey veterinary practitioners in Australia on how they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA), the treatment of OA when PPS is combined with other drugs, and the efficacy of PPS compared with other disease-modifying osteoarthritic drugs. Practitioners were contacted by email, which contained a link to an online survey. A total of 76 responses (34.5%) to the survey were received. Respondents most commonly used PPS as prophylactic therapy prior to competition (80.3%). As a prophylactic agent, PPS was considered by 48.2% of respondents to have high efficacy. The most common dose regimen for prevention and treatment of OA was 3 mg/kg, intramuscularly, once weekly for 4 weeks followed by monthly injections. Most respondents (78%) combined PPS with other drugs for treatment of OA. Intra-articular corticosteroids and hyaluronate (HA) was the most common drug combination used with PPS. PPS was preferred as a prophylactic agent when compared with HA (88.7% vs 11.3%). For treating OA, 83% of respondents considered a combination of PPS, HA and glucosamine to be more efficacious than PPS alone. However, the most common reason not to use this combination was cost (79.1%). All respondents used PPS for prophylaxis and/or treatment of OA despite limited published scientific evidence proving its efficacy in horses. Further research is necessary to provide evidence of the clinical efficacy of PPS for the prevention and treatment of OA in horses. © 2014 Australian Veterinary Association.

  12. Analysis of the Efficacy of Therapeutic Complex in Patients of Gastroenterological Profile with Candidiasis of the Mucous Membrane of the Upper Digestive Tract

    Directory of Open Access Journals (Sweden)

    I.V. Kushnirenko

    2016-10-01

    Full Text Available The problem of the treatment for candidiasis of mucosa of the upper digestive tract remains relevant because of the need of both a causal treatment, and taking into account the variability of the immune response in the interaction of the microorganism and Candida albicans. Reduced immunoreactivity in this case requires the corrective treatment. The objective — to study the effect of therapeutic complex with an inclusion of polypeptide immunomodulator imunofan on the performance of innate and adaptive immunity in patients of this group. According to the findings, patients with invasion of fungi in the mucosa are characterized by the presence of immune deficiency in terms of the ratio of white blood cells/CD3+, which is 1.3 times higher than in patients with oropharyngeal and superficial candidiasis (p < 0.01. After the treatment in the group of patients with Candida invasion of mucosa, the initially increased value of HCT test and cytochemical index of neutrophil activity were decreased by 40.40 % (p < 0.05 and 29.03 % (p < 0.05, respectively. These changes, along with increased levels of circulating immune complexes by 1.4 times compared with the values before treatment (p < 0.05 and 1.5 times — compared to controls (p < 0.01, indicate a deeper defects of the innate immunity, which obviously lead to a more severe course of disease and the difficulty in treatment. In general, the use of medical complex leads to the recovery of T-cell immunity in both groups of patients, with normalization of the T-helper/T-suppressors ratio, to an increase in the level of lactoferrin in the oral cavity and the increased concentration of IgA and IgG in patients with invasion. Therefore, a comprehensive approach to the treatment of patients with mucosal candidiasis of the upper gastrointestinal tract and determining the strategy and tactics of further observations are necessary for the effective provision of care.

  13. Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at Grand Coulee Dam Third Powerplant Forebay

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, Mary Ann; Johnson, Robert L.; McKinstry, Craig A.; Simmons, Carver S.; Cook, Chris B.; Brown, Richard S.; Tano, Daniel K.; Thorsten, Susan L.; Faber, Derrek M.; Lecaire, Richard; Francis, Stephen

    2004-01-01

    This report documents the third year of a four-year study to assess the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee salmon (Oncorhynchus nerka) and rainbow trout (O. mykiss) in the forebay to the third powerplant at Grand Coulee Dam. This work was conducted for the Bonneville Power Administration, U.S. Department of Energy, by Pacific Northwest National Laboratory (PNNL) in conjunction with the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes).

  14. Correlations of CTLA-4 Exon-1 49 A/G and Promoter Region 318 C/T Polymorphisms with the Therapeutic Efficacy of 131 I Radionuclide in Graves' Disease in Chinese Han Population.

    Science.gov (United States)

    Han, Xin-Rui; Wen, Xin; Wang, Shan; Fan, Shao-Hua; Zhuang, Juan; Wang, Yong-Jian; Zhang, Zi-Feng; Li, Meng-Qiu; Hu, Bin; Shan, Qun; Sun, Chun-Hui; Bao, Ya-Xing; Luan, Sha; Zhao, Chang-Jiu; Wu, Dong-Mei; Lu, Jun; Zheng, Yuan-Lin

    2017-08-04

    This study aimed to investigate the correlation of CTLA-4 exon-1 49 A/G and promoter region-318 C/T polymorphisms with the therapeutic efficacy of radionuclide 131 I for Graves' disease in Chinese Han population. The 131 I radionuclide therapy was applied in 261 patients with Graves' disease. The patients were classified into the remission and non-remission groups. PCR-RFLP was implemented to detect CTLA-4 exon-1 49 A/G and promoter region-318 C/T polymorphisms. Haplotypes of CTLA-4 49 A/G and -318 C/T were analyzed using SHEsis software online. Logistic regression model was applied to analyze the association between multiple factors and the efficacy of 131 I therapy. The results showed that CTLA-4 49 A/G was closely related to the efficacy of 131 I treatment for Graves' disease (AG + GG vs. AA: OR = 6.125, 95%CI = 1.431∼26.22, P = 0.006; G vs. A: OR = 2.204, 95%CI = 1.267 ∼3 .835, P = 0.004). Moreover, the findings revealed that haplotype A-C (P = 0.018, OR = 0.424, 95%CI: 0.205∼0.876) and G-C (P = 0.014, OR = 2.204, 95%CI: 1.267∼3.835) were associated with the efficacy of 131 I therapy in treating Graves' disease. Logistic regression analysis indicated that thyroid weight (OR = 1.050, 95%CI = 1.007∼1.095, P = 0.022) and CTLA-4 exon-1 49 A/G polymorphism (OR = 8.082, 95%CI = 1.049∼62.234, P = 0.045) were both related factors with efficacy of 131 I therapy in Graves' disease. These data indicated that CTLA-4 exon-1 49 A/G polymorphism may be associated with therapeutic efficacy of radionuclide 131 I for patients with Graves' disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. ICD implantation without intraoperative testing does not increase the rate of system modifications and does not impair defibrillation efficacy tested in follow-up.

    Science.gov (United States)

    Bastian, Dirk; Kracker, Stefan; Pauschinger, Matthias; Göhl, Konrad

    2013-06-01

    The need for implantable cardioverter-defibrillator (ICD) defibrillation testing (DT) and subsequent intraoperative system modifications is discussed controversially. The study's goal was to prove that consequent abdication of intraoperative DT does not impair defibrillation efficacy and does not increase the rate of postoperative system revisions. In a prospective single-center observational study, 609 out of 648 consecutive patients underwent transvenous ICD implantation (left-sided, active can, dual coil lead, and biphasic shock waveform) waiving intraoperative DT. Defibrillation efficacy was validated prior to hospital discharge (PHD) by applying two 10 J safety margin (SM) shocks. Following "schockless" implantation 580 out of 609 patients (95.2 %) met a 10 J SM with default programming. Shock path reversal provided 10 J SM in 13 out of 29 cases with initially failed DT. In four patients (0.7 %) maximum energy shocks were ineffective. There was no morbidity or mortality related to DT. The total rate of surgical ICD revisions was 1.8 %. Routine ICD implantation without intraoperative DT does not lead to an increased rate of postoperative system modifications and does not decrease defibrillation efficacy as tested PHD.

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

    NARCIS (Netherlands)

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

    2015-01-01

    Quantification of tumor necrosis in cancer patients is of diagnostic value as the amount of necrosis is correlated with disease prognosis and it could also be used to predict early efficacy of anti-cancer treatments. In the present study, we identified two near infrared fluorescent (NIRF)

  17. Relationship of Self-Efficacy Beliefs of Urban Public School Students to Performance on a High-Stakes Mathematics Test

    Science.gov (United States)

    Afolabi, Kolajo A.

    2010-01-01

    The purpose of this study was to examine the relationship of "self-efficacy" for "Enlisting Social Resources, Self-Regulatory Efficacy, self-efficacy" for "Self-Regulated Learning," and "self-efficacy" for "Academic Achievement" (Bandura's Children's "Self-Efficacy Scale," 2006) of urban…

  18. Evaluation of efficacy of some serological tests used for diagnosis of ...

    African Journals Online (AJOL)

    These samples were subjected to the different serological tests including Rose Bengal plate antigen test, Tube Agglutination test, Rivanol test, Indirect Enzyme Linked Immunosorbent Assay and Competitive Enzyme Linked Immunosorbent Assay. Statistical analysis of the obtained results in different cattle groups was ...

  19. Beta lactam antibiotics residues in cow's milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina

    Directory of Open Access Journals (Sweden)

    Nihad Fejzic

    2014-08-01

    Full Text Available Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis.  Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow’s milk in our country. The tests used in the study are SNAP β Lactam test (Idexx, Rosa Charm β Lactam test and Inhibition MRL test. Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb. In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis. Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level – MLR. Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues.

  20. Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma

    Directory of Open Access Journals (Sweden)

    Mouadh Benamar

    2016-08-01

    Research in Context: The identification of new molecular targets and effective inhibitors is of utmost significance for the clinical management of melanoma. This study identifies CDT2, a substrate receptor for the CRL4 ubiquitin ligase, as a prognostic marker and therapeutic target in melanoma. CDT2 is required for melanoma cell proliferation and inhibition of CRL4CDT2 by pevonedistat suppresses melanoma in vitro and in vivo through the induction of DNA rereplication and senescence through the stabilization of the CRL4CDT2 substrates p21 and SET8. Pevonedistat also synergizes with vemurafenib in vivo and suppresses vemurafenib-resistant melanoma cells. These findings show a significant promise for targeting CRL4CDT2 therapeutically.

  1. Therapeutic efficacy and safety of oral tranexamic acid and that of tranexamic acid local infiltration with microinjections in patients with melasma: a comparative study.

    Science.gov (United States)

    Sharma, R; Mahajan, V K; Mehta, K S; Chauhan, P S; Rawat, R; Shiny, T N

    2017-10-01

    Tranexamic acid (TXA) has been used orally, intravenously, topically and intradermally (microinjection, microneedling) for treating melasma. However, the comparative efficacy of these different routes of administration remains underevaluated. To ascertain the comparative efficacy of different routes of administration of TXA. In total, 100 consecutive patients with melasma (8 men, 92 women, age range 18-55 years) were randomly assigned to one of two groups comprising 50 patients each. Group A (3 men, 47 women) received oral TXA 250 mg twice daily, while group B (5 men, 45 women) received intradermal microinjections of TXA 4 mg/mL every 4 weeks. The treatment continued for 12 weeks in both groups. Percentage reduction in baseline Melasma Area and Severity Index (MASI) was assessed at 4-week intervals, and response was scored as very good (> 75% reduction), good (50% to melasma, irrespective of its route of administration. © 2017 British Association of Dermatologists.

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

    OpenAIRE

    Vandervert, Larry

    2015-01-01

    Background 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...

  3. Developing and Testing the Short-Form Knowledge, Efficacy, and Practices Instrument for Assessing Cultural Competence.

    Science.gov (United States)

    Garvan, Gerard J; Garvan, Cynthia W; Behar-Horenstein, Linda S

    2016-10-01

    The importance of educating dental students in cultural competence has been widely emphasized, but there is a need to assess cultural competence in a consistent and reliable way. The aims of this study were to determine latent constructs for the initial measure of cultural competence for oral health providers, the Knowledge, Efficacy, and Practices Instrument (KEPI), and to determine how well these factors related to previously identified latent constructs. Data were collected in surveys of dental students and from dental hygiene, dental assisting, and dental faculty members in 44 academic dental institutions from 2012 to 2015. There were a total of 1,786 respondents to the surveys; response rates to individual surveys ranged from 35% to 100%. There were 982 (55%) female and 804 (45%) male respondents, 286 (16%) underrepresented minority (URM) and 1,500 (84%) non-URM respondents, and 339 (19%) faculty and 1,447 (81%) student respondents. Three latent constructs were identified. Female respondents scored significantly higher on the culture-centered practice and efficacy of assessment factors, while URM respondents had significantly higher scores on all three of the KEPI factors. Measurements indicated that the long-form KEPI could be shortened by ten questions and still have three meaningful measurements. Continued research in assessing other health care providers' cultural competence is needed to expand the KEPI to measure providers' cultural competence with patients with minority sexual orientation and gender identity issues and those with physical disabilities, mental illness, and autism to advance patient-centric communication.

  4. Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model.

    Science.gov (United States)

    Mestas, Jean-Louis; Fowler, R Andrew; Evjen, Tove J; Somaglino, Lucie; Moussatov, Alexei; Ngo, Jacqueline; Chesnais, Sabrina; Røgnvaldsson, Sibylla; Fossheim, Sigrid L; Nilssen, Esben A; Lafon, Cyril

    2014-09-01

    The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.

  5. Restoring microenvironmental redox and pH homeostasis inhibits neoplastic cell growth and migration: therapeutic efficacy of esomeprazole plus sulfasalazine on 3-MCA-induced sarcoma

    Science.gov (United States)

    Moreno, Paola Sanchez; Piccioli, Patrizia; Medraño-Fernandez, Iria; Semino, Claudia; Rubartelli, Anna

    2017-01-01

    Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole. Sulfasalazine inhibited the cystine/cysteine redox cycle and esomeprazole decreased pHi while increasing pHe in tumor cell lines. Although the single treatment with either drug slightly inhibited cell proliferation and motility, the association of sulfasalazine and esomeprazole powerfully decreased sarcoma and melanoma growth and migration. In the 3-methylcholanthrene (3-MCA)-induced sarcoma model, the combined therapy strongly reduced the tumor burden and increased the survival time: notably, 22 % of double-treated mice recovered and survived off therapy. Tumor-associated macrophages (TAM) displaying M2 markers, that abundantly infiltrate sarcoma and melanoma, overexpress xc- and membrane v-ATPases and were drastically decreased in tumors from mice undergone the combined therapy. Thus, the double targeting of tumor cells and macrophages by sulfasalazine and esomeprazole has a double therapeutic effect, as decreasing TAM infiltration deprives tumor cells of a crucial allied. Sulfasalazine and esomeprazole may therefore display unexpected therapeutic values, especially in case of hard-to-treat cancers. PMID:28978047

  6. A review of technology-assisted self-help and minimal contact therapies for anxiety and depression: is human contact necessary for therapeutic efficacy?

    Science.gov (United States)

    Newman, Michelle G; Szkodny, Lauren E; Llera, Sandra J; Przeworski, Amy

    2011-02-01

    Technology-based self-help and minimal contact therapies have been proposed as effective and low-cost interventions for anxiety and mood disorders. The present article reviews the literature published before 2010 on these treatments for anxiety and depression using self-help and decreased therapist-contact interventions. Treatment studies are examined by disorder as well as amount of therapist contact, ranging from self-administered therapy and predominantly self-help interventions to minimal contact therapy where the therapist is actively involved in treatment but to a lesser degree than traditional therapy and predominantly therapist-administered treatments involving regular contact with a therapist for a typical number of sessions. In the treatment of anxiety disorders, it is concluded that self-administered and predominantly self-help interventions are most effective for motivated clients. Conversely, minimal-contact therapies have demonstrated efficacy for the greatest variety of anxiety diagnoses when accounting for both attrition and compliance. Additionally, predominantly self-help computer-based cognitive and behavioral interventions are efficacious in the treatment of subthreshold mood disorders. However, therapist-assisted treatments remain optimal in the treatment of clinical levels of depression. Although the most efficacious amount of therapist contact varies by disorder, computerized treatments have been shown to be a less-intensive, cost-effective way to deliver empirically validated treatments for a variety of psychological problems. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Testing a Longitudinal Integrated Self-Efficacy and Self-Determination Theory Model for Physical Activity Post-Cardiac Rehabilitation.

    Science.gov (United States)

    Sweet, Shane N; Fortier, Michelle S; Strachan, Shaelyn M; Blanchard, Chris M; Boulay, Pierre

    2014-01-13

    Self-determination theory and self-efficacy theory are prominent theories in the physical activity literature, and studies have begun integrating their concepts. Sweet, Fortier, Strachan and Blanchard (2012) have integrated these two theories in a cross-sectional study. Therefore, this study sought to test a longitudinal integrated model to predict physical activity at the end of a 4-month cardiac rehabilitation program based on theory, research and Sweet et al.'s cross-sectional model. Participants from two cardiac rehabilitation programs (N=109) answered validated self-report questionnaires at baseline, two and four months. Data were analyzed using Amos to assess the path analysis and model fit. Prior to integration, perceived competence and self-efficacy were combined, and labeled as confidence. After controlling for 2-month physical activity and cardiac rehabilitation site, no motivational variables significantly predicted residual change in 4-month physical activity. Although confidence at two months did not predict residual change in 4-month physical activity, it had a strong positive relationship with 2-month physical activity (β=0.30, Pself-determination and self-efficacy theory were still partially supported. Because the model had good fit, this study demonstrated that theoretical integration is feasible.

  8. Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model.

    Science.gov (United States)

    Monroy-García, Alberto; Gómez-Lim, Miguel Angel; Weiss-Steider, Benny; Hernández-Montes, Jorge; Huerta-Yepez, Sara; Rangel-Santiago, Jesús F; Santiago-Osorio, Edelmiro; Mora García, María de Lourdes

    2014-02-01

    HPV L1-based virus-like particles vaccines (VLPs) efficiently induce temporary prophylactic activity through the induction of neutralizing antibodies; however, VLPs that can provide prophylactic as well as therapeutic properties for longer periods of time are needed. For this purpose, we generated a novel HPV 16 L1-based chimeric virus-like particle (cVLP) produced in plants that contains a string of T-cell epitopes from HPV 16 E6 and E7 fused to its C-terminus. In the present study, we analyzed the persistence of specific IgG antibodies with neutralizing activity induced by immunization with these cVLPs, as well as their therapeutic potential in a tumor model of C57BL/6 mice. We observed that these cVLPs induced persistent IgG antibodies for over 12 months, with reactivity and neutralizing activity for VLPs composed of only the HPV-16 L1 protein. Efficient protection for long periods of time and inhibition of tumor growth induced by TC-1 tumor cells expressing HPV-16 E6/E7 oncoproteins, as well as significant tumor reduction (57 %), were observed in mice immunized with these cVLPs. Finally, we discuss the possibility that chimeric particles of the type described in this work may be the basis for developing HPV prophylactic and therapeutic vaccines with high efficacy.

  9. Determination of the safety and efficacy of therapeutic neutralization of tumor necrosis factor-α (TNF-α) using AZD9773, an anti-TNF-α immune Fab, in murine CLP sepsis.

    Science.gov (United States)

    Newham, Peter; Ross, Daniel; Ceuppens, Peter; Das, Shampa; Yates, James W T; Betts, Catherine; Reens, Jaimini; Randall, Kevin J; Knight, Richard; McKay, Jennifer S

    2014-02-01

    TNF-α neutralization is associated with increased mortality in mouse cecal ligation puncture (CLP) models. AZD9773 is an ovine polyclonal human TNF-α immune Fab, with pharmacological properties that differ from previously studied anti-TNF-α agents. We explored the safety and efficacy of therapeutically administered AZD9773 in mouse CLP sepsis. A moderate/severe-grade CLP model resulting in 20-30 % 5-day survival and a mild-grade CLP model resulting in ~70 % 5-day survival were established in human TNF-α transgene/murine TNF null (Tg1278/-/-) mice. Mice received saline resuscitation and imipenem administration every 12 h (0-72 h post-CLP). AZD9773 (or DigiFab control) was dosed 24, 36, 48 and 60 h post-CLP. Therapeutic dosing of AZD9773 in moderate/severe-grade CLP resulted in significantly increased survival (>70 %) compared with DigiFab (27 %, P CLP did not significantly affect survival outcome compared with DigiFab or imipenem alone (~60-70 % survival). These data demonstrate that TNF-α neutralization can improve survival in moderate/severe CLP sepsis. TNF-α suppression in mild-grade models was not associated with survival benefit and did not increase 5-day mortality. These findings suggest that therapeutic benefit following TNF-α attenuation in models of sepsis may depend on model severity.

  10. Usage of ultraviolet test method for monitoring the efficacy of surgical hand rub technique among medical students.

    Science.gov (United States)

    Vanyolos, Erzsebet; Peto, Katalin; Viszlai, Aida; Miko, Iren; Furka, Istvan; Nemeth, Norbert; Orosi, Piroska

    2015-01-01

    Adequate hand movements are essential in surgical hand rub, so it is important for medical students to learn it correctly. To assess its efficacy, we aimed to use ultraviolet (UV) light test after applying fluorescent solution. Digital images of the hands of 253 medical students were analyzed during "Basic Surgical Techniques" course on the 10th (Survey 1) and 14th (Survey 2) week of the curriculum to check the process and the skills development. The last step of the surgical hand rub was performed with a fluorescent solution, and then the hands were placed under UV light. Photographs were taken and analyzed. Every uncovered area was considered an error. Number and the localization of missed spots and its extent was determined. For evaluation, palmar (P) and dorsal (D) sides of the hands were divided into regions of interest (1-distal phalanxes, 2-thumb and first metacarpus, 3-second to fifth fingers, and 4-second to fifth metacarpals). Various magnitude and number of failure occurred in 123 (48.61%) students in survey 1 and in 65 (25.69%) in survey 2. The most frequent sites of the missed spots were D/2 and P/4 region in survey 1 and D/1 and P/4 in survey 2. There was an improvement seen in survey 2, as shown by a decrease in the number and extent of missed spots. Right-handed students made fewer mistakes on their nondominant hands than left-handed students (n = 23) did. The method was suitable to monitor the efficacy of surgical hand rub technique and identify the mistakes and the critical sites. The main advantage of the UV test was the immediate feedback, which resulted in a distinct improvement. Applying the UV test to the medical education and training may contribute to improvement in the compliance and the efficacy of the technique of surgical hand rub among the students. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  11. A cluster-randomised controlled trial to test the efficacy of facemasks in preventing respiratory viral infection among Hajj pilgrims.

    Science.gov (United States)

    Wang, Mandy; Barasheed, Osamah; Rashid, Harunor; Booy, Robert; El Bashir, Haitham; Haworth, Elizabeth; Ridda, Iman; Holmes, Edward C; Dwyer, Dominic E; Nguyen-Van-Tam, Jonathan; Memish, Ziad A; Heron, Leon

    2015-06-01

    Cost-effective interventions are needed to control the transmission of viral respiratory tract infections (RTIs) in mass gatherings. Facemasks are a promising preventive measure, however, previous studies on the efficacy of facemasks have been inconclusive. This study proposes a large-scale facemask trial during the Hajj pilgrimage in Saudi Arabia and presents this protocol to illustrate its feasibility and to promote both collaboration with other research groups and additional relevant studies. A cluster-randomised controlled trial is being conducted to test the efficacy of standard facemasks in preventing symptomatic and proven viral RTIs among pilgrims during the Hajj season in Mina, Mecca, Saudi Arabia. The trial will compare the 'supervised use of facemasks' versus 'standard measures' among pilgrims over several Hajj seasons. Cluster-randomisation will be done by accommodation tents with a 1:1 ratio. For the intervention tents, free facemasks will be provided to be worn consistently for 7days. Data on flu-like symptoms and mask use will be recorded in diaries. Nasal samples will be collected from symptomatic recruits and tested for nucleic acid of respiratory viruses. Data obtained from questionnaires, diaries and laboratory tests will be analysed to examine whether mask use significantly reduces the frequency of laboratory-confirmed respiratory viral infection and syndromic RTI as primary outcomes. This trial will provide valuable evidence on the efficacy of standard facemask use in preventing viral respiratory tract infections at mass gatherings. This study is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12613001018707 (http://www.anzctr.org.au). Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  12. Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals.

    Science.gov (United States)

    Narmada, Balakrishnan Chakrapani; Goh, Yeek Teck; Li, Huan; Sinha, Sanjay; Yu, Hanry; Cheung, Christine

    2017-03-01

    Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti-inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin-1β owing to limited metabolic activity of hPSC-ECs. Conversely, hPSC-HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC-HEPs were cocultured with hPSC-ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin-1β stimulation on hPSC-ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin-8 production. Thus, integration of hPSC-HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial-hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular-targeting candidate compounds. Stem Cells Translational Medicine 2017;6:851-863. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  13. Anthelminthic efficacy of banana crop residues on gastrointestinal nematodes of sheep: in vitro and in vivo tests.

    Science.gov (United States)

    Nogueira, Flávia Aparecida; Oliveira, Lincoln Nunes; da Silva, Rayana Brito; Nery, Patrícia Silva; Virgínio, Gercino Ferreira; Geraseev, Luciana Castro; Duarte, Eduardo Robson

    2012-07-01

    Resistance to anthelminthics is common due to intensive and incorrect use. In searching for alternatives, extracts of banana plant were evaluated for egg hatching inhibition and fecal egg count reduction of sheep nematodes. Aqueous extracts of the leaf, pseudostem, and heart of the banana plant cv. Prata anã were tested at concentrations of 0.31, 0.62, 1.25, 2.5, 5.0, and 10.0 mg ml(-1) in egg hatching inhibition tests. For in vivo analysis, aqueous extracts were evaluated at dosages calculated according to the 10% lethal dose derived from acute toxicity testing in mice. Efficacy was evaluated at two time periods following oral administration. For the banana extracts at 2.5 mg ml(-1), egg hatching was significantly fewer than the negative control, with an LC(50) and LC(90) of 0.19 and 0.84 mg ml(-1), respectively. In vivo analysis for weeks 1 and 2 following a single treatment with aqueous leaf extract showed 33.1% and 32.5% anthelminthic efficacy, respectively. Further research on higher dosages with more frequent administration is needed to evaluate the potential for utilizing banana plant residues in gastrointestinal nematode control.

  14. Efficacy of Structured Organizational Change Intervention on HIV Testing in Correctional Facilities.

    Science.gov (United States)

    Belenko, Steven; Visher, Christy; Pearson, Frank; Swan, Holly; Pich, Michele; O'Connell, Daniel; Dembo, Richard; Frisman, Linda; Hamilton, Leah; Willett, Jennifer

    2017-06-01

    This article presents findings from a multisite cluster randomized trial of a structured organizational change intervention for improving HIV testing services in jails and prisons. Matched pairs of prison and jail facilities were randomized to experimental and control conditions; all facilities received baseline training about best practices in HIV testing and other HIV services and selected an area of HIV services on which to focus improvement efforts. The experimental facilities formed local change teams and were provided external coaching based on the Network for the Improvement of Addiction Treatment (NIATx) process improvement model. Difference-indifference analyses indicate a significant relative increase in HIV testing in the experimental compared to the control condition. Meta-analyses across the matched pairs indicated a small to medium effect of increased testing overall. The results indicate that the local change team model can achieve significant increases in HIV testing in correctional facilities. Implications for HIV testing policies and challenges for expanding testing are discussed.

  15. Therapeutic Vaccines for Chronic Infections

    Science.gov (United States)

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

    2004-07-01

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

  16. Short Communication: In Vitro Efficacy Testing of Praziquantel, Ivermectin, and Oxfendazole against Taenia Solium Cysts

    Directory of Open Access Journals (Sweden)

    S. Cederberg

    2012-01-01

    Full Text Available Oxfendazole is recommended as the drug of choice for treating porcine cysticercosis. The drug does not kill brain cysts and is not registered for use in pigs. Latest its safety in the recommended dose has been questioned. The aim of this study was to investigate two alternative anthelminthics. The efficacy of praziquantel and ivermectin was compared to oxfendazole In Vitro on Taenia solium. Cysts of T. solium were isolated from infected pork and incubated in culture media together with the drugs. The degree of evagination was used as effect measurement and determined after 6 hours. Praziquantel had a half maximal effective concentration (EC50 of value 0.006 ± 0.001 μg/mL. Ivermectin did not show any impact on the evagination in concentrations from 0.001 to 30 μg/mL and neither did oxfendazole in concentrations from 0.001 to 50 μg/mL.

  17. Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

    Science.gov (United States)

    Faisal, Amir; Mak, Grace W Y; Gurden, Mark D; Xavier, Cristina P R; Anderhub, Simon J; Innocenti, Paolo; Westwood, Isaac M; Naud, Sébastien; Hayes, Angela; Box, Gary; Valenti, Melanie R; De Haven Brandon, Alexis K; O'Fee, Lisa; Schmitt, Jessica; Woodward, Hannah L; Burke, Rosemary; vanMontfort, Rob L M; Blagg, Julian; Raynaud, Florence I; Eccles, Suzanne A; Hoelder, Swen; Linardopoulos, Spiros

    2017-04-25

    The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850.

  18. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Kidd, M. [Wren Laboratories, Branford, CT (United States); Modlin, I.M. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Yale School of Medicine, New Haven, CT (United States); Severi, S.; Nicolini, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Drozdov, I. [Bering Limited, London (United Kingdom); Kwekkeboom, D.J.; Krenning, E.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Erasmus Medical Center, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2016-05-15

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with {sup 177}Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 {sup 18}FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ{sup 2} = 27.4; p = 1.2 x 10{sup -7}) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0

  19. A randomized clinical trial to test the efficacy of a family-focused, culturally informed therapy for schizophrenia.

    Science.gov (United States)

    Weisman de Mamani, Amy; Weintraub, Marc J; Gurak, Kayla; Maura, Jessica

    2014-12-01

    Research strongly suggests that family interventions can benefit patients with schizophrenia, yet current interventions often fail to consider the cultural context and spiritual practices that may make them more effective and relevant to ethnic minority populations. We have developed a family focused, culturally informed treatment for schizophrenia (CIT-S) patients and their caregivers to address this gap. Sixty-nine families were randomized to either 15 sessions of CIT-S or to a 3-session psychoeducation (PSY-ED) control condition. Forty-six families (66.7%) completed the study. The primary aim was to test whether CIT-S would outperform PSY-ED in reducing posttreatment symptom severity (controlling for baseline symptoms) on the Brief Psychiatric Rating Scale. Secondary analyses were conducted to test whether treatment efficacy would be moderated by ethnicity and whether patient-therapist ethnic match would relate to efficacy and patient satisfaction with treatment. Patients included 40 Hispanic/Latinos, 14 Whites, 11 Blacks, and 4 patients who identified as "other." In line with expectations, results from an ANCOVA indicated that patients assigned to the CIT-S condition had significantly less severe psychiatric symptoms at treatment termination than did patients assigned to the PSY-ED condition. Patient ethnicity and patient-therapist ethnic match (vs. mismatch) did not relate to treatment efficacy or satisfaction with the intervention. Results suggest that schizophrenia may respond to culturally informed psychosocial interventions. The treatment appears to work equally well for Whites and minorities alike. Follow-up research with a matched length control condition is needed. Further investigation is also needed to pinpoint specific mechanisms of change.

  20. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels.

    Science.gov (United States)

    Hawes, E M; Deal, A M; Funk-Adcock, D; Gosselin, R; Jeanneret, C; Cook, A M; Taylor, J M; Whinna, H C; Winkler, A M; Moll, S

    2013-08-01

    Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations. To determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect. Peak and trough blood samples from 35 patients taking dabigatran 150 mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected. Mass spectrometry and various coagulation assays were performed. 'Therapeutic range' was defined as the range of plasma dabigatran concentrations determined by mass spectrometry between the 2.5th and 97.5th percentiles of all values. The therapeutic range was 27-411 ng mL(-1) . The prothrombin time (PT) and activated partial thromboplastin time (APTT), determined with multiple reagents, and activated clotting time (ACT) were insensitive to therapeutic dabigatran: 29%, 18% and 40% of samples had a normal PT, APTT, and ACT, respectively. However, normal PT, ACT and APTT ruled out dabigatran levels above the 75th percentile. The thrombin clotting time (TCT) correlated well and linearly with dabigatran levels below the 50th percentile, but was unmeasurable above it. The dilute thrombin time, ecarin clotting time and ecarin chromogenic assay showed linear correlations with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. The prothrombin time, APTT and ACT are often normal in spite of therapeutic dabigatran plasma levels. The TCT is useful for detecting minimal dabigatran levels. The dilute thrombin time and chromogenic and clotting ecarin assays accurately identify therapeutic and supratherapeutic dabigatran levels. This trial is registered at www.clinicaltrials.gov (#NCT01588327). © 2013 International Society on Thrombosis and Haemostasis.

  1. Gender Fair Efficacy of Concept Mapping Tests in Identifying Students' Difficulties in High School Organic Chemistry

    Science.gov (United States)

    Gafoor, Kunnathodi Abdul; Shilna, V.

    2014-01-01

    In view of the perceived difficulty of organic chemistry unit for high schools students, this study examined the usefulness of concept mapping as a testing device to assess students' difficulty in the select areas. Since many tests used for identifying students misconceptions and difficulties in school subjects are observed to favour one or the…

  2. [Determination of the diagnostic efficacy of the multi-RAST test (Phadiotop) in allergic rhinitis].

    Science.gov (United States)

    Bujía, J; Rasp, G

    1995-01-01

    Diagnosis of IgE mediated allergic rhinitis is based on medical history. Prick-test (of the skin) and determination of increased IgE levels by serum (PRIST and RAST) as well as intranasal provocation test. To search the potential diagnostic value of a multi-RAST test (Phadiotop) in serum and nasal fluids, 508 with rhinitis were studied: In 267 patients nasal allergy was confirmed by the above mentioned tests. Phadiotop revealed a sensitivity of 98.1% in serum and 79.0% in nasal fluid. Specificity of Phadiotop was 95.9% in serum and 97.5% in nasal fluid. Our results show that the determination of Phadiotop can be considered as a very sensitive screening test for allergy detection.

  3. Efficacy of antibiotic treatment and test-based culling strategies for eradicating brucellosis in commercial swine herds.

    Science.gov (United States)

    Dieste-Pérez, L; Frankena, K; Blasco, J M; Muñoz, P M; de Jong, M C M

    2016-04-01

    Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in continental Europe. Without effective vaccines being available, the European Food Safety Authority (EFSA) recommends the full depopulation of infected herds as the only strategy to eradicate B. suis outbreaks. Using data collected from 8 herds suffering natural swine brucellosis outbreaks, we assessed the efficacy of four control strategies: (i) oxytetracycline treatment only, as a default scenario, (ii) oxytetracycline treatment combined with skin testing and removal of positive animals, (iii) oxytetracycline treatment combined with serological testing (Rose Bengal test-RBT-and indirect ELISA -iELISA-) and removal of seropositive animals and (iv) oxytetracycline treatment combined with both serological (RBT/iELISA) and skin testing and removal of positive animals. A Susceptible-Infectious-Removal model was used to estimate the reproduction ratio (R) for each strategy. According to this model, the oxytetracycline treatment alone was not effective enough to eradicate the infection. However, this antibiotic treatment combined with diagnostic testing at 4-monthly intervals plus immediate removal of positive animals showed to be effective to eradicate brucellosis independent of the diagnostic test strategy used in an acceptable time interval (1-2 years), depending on the initial number of infected animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Phenolic compounds based conjugates from dextran aldehyde and BSA: Preparation, characterization and evaluation of their anti-cancer efficacy for therapeutic applications.

    Science.gov (United States)

    Rai, Sudheer; Kureel, Amit Kumar; Dutta, P K; Mehrotra, G K

    2017-11-10

    Here, we have synthesized phenolic compounds (pc) based on conjugates from dextran aldehyde (dex-ald) and bovine serum albumin (BSA) and screening their potential activity as therapeutic agents in cancer disease. The synthesized conjugates were analyzed by UV-vis, FT-IR, XRD and SEM analysis. UV-vis spectra of conjugates showed the shifting of spectral peak at UV to visible region revealed the enhanced conjugation due to formation of linkage. The XRD peaks of conjugates found broader and indicating the amorphous phase of conjugating materials in compared to free components. The SEM images showed that the conjugated materials having numerous pores on its surface, which proved its porous nature. The amount of phenolic compounds conjugated with (dex-ald-pc) and (BSA-pc) were found to be 65.4 and 73.91mg/g of conjugates, respectively. Cells viability was significantly decreased approximately 80-85% at concentration of 100μg conjugates whereas the free polymers or phenolics did not affect the viability of cancer cells. Generation of high quantity of reactive oxygen species (ROS) in cells treated with conjugate materials, which may caused cell apoptosis in cancer cell line. The results clearly showed that conjugation of phenolic compounds were an effective method to improve the functional properties for therapeutic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  6. Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy

    Science.gov (United States)

    Minassian, Angela M.; Ronan, Edward O.; Poyntz, Hazel; Hill, Adrian V. S.; McShane, Helen

    2011-01-01

    There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection. PMID:21629699

  7. Clinical Efficacy Test of Polyester Containing Herbal Extract Dressings in Burn Wound Healing.

    Science.gov (United States)

    Muangman, Pornprom; Praditsuktavorn, Banjerd; Chinaroonchai, Kusuma; Chuntrasakul, Chomchark

    2016-09-01

    Technological advancement has assisted in developing various availabilities of wound products that help in not only in healing and preventing infection but also in providing patients' comfort and pain reduction during application. However, most of advanced wound healing products in Thailand were imported at high costs to patients. Nowadays, there are increased numbers of local researches of herbs that could provide healing environment for successful wound care. Herbal wound products are currently being introduced as alternatives to those imported dressings. The aim of this study was to report the clinical efficacy of using polyester containing herbal extract dressings in healing of second-degree burns. The volunteers were divided by simply randomized method into the study group of patient using polyester containing herbal extract dressing and the control group of patients treating with dressings that are commercially available and common use. The standard treatment protocols were performed at every 3 days of dressing change. Comparative evaluation consisted of time of healing, length of hospital stays, pain analog score assessment, percentage of infection, and descriptive notification of unfavorable clinical symptoms or signs or side effects. © The Author(s) 2016.

  8. Development in Assay Methods for in Vitro Antimalarial Drug Efficacy Testing: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Shweta Sinha

    2017-10-01

    Full Text Available The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000–2,000,000 compounds per screening campaign, before pre-clinical trials to select optimum lead. Carrying out in vitro screening of antimalarials is very difficult as different assay methods are subject to numerous sources of variability across different laboratories around the globe. Despite this, in vitro screening is an essential part of antimalarial drug development as it enables to resource various confounding factors such as host immune response and drug–drug interaction. Therefore, in this article, we try to illustrate the basic necessity behind in vitro study and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of in vitro screening based on the current approaches (such as stem cells.

  9. An investigation of the efficacy of collaborative virtual reality systems for moderated remote usability testing.

    Science.gov (United States)

    Chalil Madathil, Kapil; Greenstein, Joel S

    2017-11-01

    Collaborative virtual reality-based systems have integrated high fidelity voice-based communication, immersive audio and screen-sharing tools into virtual environments. Such three-dimensional collaborative virtual environments can mirror the collaboration among usability test participants and facilitators when they are physically collocated, potentially enabling moderated usability tests to be conducted effectively when the facilitator and participant are located in different places. We developed a virtual collaborative three-dimensional remote moderated usability testing laboratory and employed it in a controlled study to evaluate the effectiveness of moderated usability testing in a collaborative virtual reality-based environment with two other moderated usability testing methods: the traditional lab approach and Cisco WebEx, a web-based conferencing and screen sharing approach. Using a mixed methods experimental design, 36 test participants and 12 test facilitators were asked to complete representative tasks on a simulated online shopping website. The dependent variables included the time taken to complete the tasks; the usability defects identified and their severity; and the subjective ratings on the workload index, presence and satisfaction questionnaires. Remote moderated usability testing methodology using a collaborative virtual reality system performed similarly in terms of the total number of defects identified, the number of high severity defects identified and the time taken to complete the tasks with the other two methodologies. The overall workload experienced by the test participants and facilitators was the least with the traditional lab condition. No significant differences were identified for the workload experienced with the virtual reality and the WebEx conditions. However, test participants experienced greater involvement and a more immersive experience in the virtual environment than in the WebEx condition. The ratings for the virtual

  10. Cost and Efficacy Assessment of an Alternative Medication Compliance Urine Drug Testing Strategy.

    Science.gov (United States)

    Doyle, Kelly; Strathmann, Frederick G

    2017-02-01

    This study investigates the frequency at which quantitative results provide additional clinical benefit compared to qualitative results alone. A comparison between alternative urine drug screens and conventional screens including the assessment of cost-to-payer differences, accuracy of prescription compliance or polypharmacy/substance abuse was also included. In a reference laboratory evaluation of urine specimens from across the United States, 213 urine specimens with provided prescription medication information (302 prescriptions) were analyzed by two testing algorithms: 1) conventional immunoassay screen with subsequent reflexive testing of positive results by quantitative mass spectrometry; and 2) a combined immunoassay/qualitative mass-spectrometry screen that substantially reduced the need for subsequent testing. The qualitative screen was superior to immunoassay with reflex to mass spectrometry in confirming compliance per prescription (226/302 vs 205/302), and identifying non-prescription abuse (97 vs 71). Pharmaceutical impurities and inconsistent drug metabolite patterns were detected in only 3.8% of specimens, suggesting that quantitative results have limited benefit. The percentage difference between the conventional testing algorithm and the alternative screen was projected to be 55%, and a 2-year evaluation of test utilization as a measure of test order volume follows an exponential trend for alternative screen test orders over conventional immunoassay screens that require subsequent confirmation testing. Alternative, qualitative urine drug screens provide a less expensive, faster, and more comprehensive evaluation of patient medication compliance and drug abuse. The vast majority of results were interpretable with qualitative results alone indicating a reduced need to automatically reflex to quantitation or provide quantitation for the majority of patients. This strategy highlights a successful approach using an alternative strategy for both the

  11. KOMPOSISI GIZI DAN DAYA TERIMA MAKANAN TERAPI: READY TO USE THERAPEUTIC FOOD UNTUK BALITA GIZI BURUK (NUTRITION COMPOSITION AND ACCEPTANCE TEST OF READY TO USE THERAPEUTIC FOOD FOR SEVERE MALNOURISHED CHILDREN

    Directory of Open Access Journals (Sweden)

    Komari Komari

    2012-12-01

    Full Text Available Abstract Severe malnourished children need special diet which is nutritious, easily digested, and safe to improve their nutritional status. The diet could be Ready-to-Use Therapeutic Food (RUTF, composed by highly digestible component such as milk, vegetable oil, sugar, vitamines, minerals, and indigenous food such as peanut, mungbean and tempeh powder. This study was aimed to examine the nutrients content and the sensory quality of local RUTF. The method utilised were acceptability test on severe malnourished children, chemical analyses to identify nutrient content and safety analysis towards microbial and heavy metal contaminants. The  results showed that RUTF contained energy ranging from 521 kcal /100 g to 530 kcal/100 g, and protein ranging from 14,1 g/100 g to 16,9 g/100g. The RUTF was acceptable by malnourished children under five years old. Keywords: ready to use, therapeutic food, malnourished Abstrak Anak gizi buruk memerlukan diet yang khusus untuk meningkatkan status gizinya dengan makanan yang mudah dicerna, bergizi tinggi dan aman. Makanan tersebut dapat berupa Ready to Use Therapeutic Food (RUTF yang terdiri dari bahan yang mudah dicerna seperti susu, minyak sayur, gula, vitamin dan mineral, dan menggunakan bahan makanan lokal yakni tepung kacang tanah, kacang hijau, dan tempe. Penelitian ini bertujuan menilai komposisi zat gizi dan kualitas sensori produk RUTF lokal. Metode yang digunakan adalah uji daya terima yang dilakukan terhadap anak balita gizi buruk, uji kimia untuk mengukur komposisi gizi dan keamanan terhadap mikroba dan logam berat. Hasil menunjukkan bahwa komposisi gizi untuk RUTF mengandung cukup tinggi energi  yaitu berkisar antara 521-530 kkal/100g dan protein berkisar antara 14,1-16,9 g/100g. Makanan tersebut juga dapat diterima oleh  anak-anak balita gizi buruk. [Penel Gizi Makan 2012, 35(2: 159-167] Kata Kunci: ready to use, makanan terapi, gizi buruk

  12. Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models.

    Science.gov (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-10-13

    Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis.

  13. Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model.

    Directory of Open Access Journals (Sweden)

    Yuka Nagata

    Full Text Available Oral immunotherapy (OIT has been considered a promising approach for food allergies (FAs. However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT. The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount. Allergic symptoms decreased in the OIT-treated FA mice. OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased the level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma. Moreover, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, and the combination therapy further suppressed the Th2 immune responses and the mast cell degranulation. In addition, OIT significantly increased the population of Foxp3+ CD4+ regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto. Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon. These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment.

  14. Bone defect animal models for testing efficacy of bone substitute biomaterials

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    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  15. Testing the margin of appreciation: therapeutic abortion, reproductive 'rights' and the intriguing case of Tysiqc v. Poland.

    Science.gov (United States)

    Priaulx, Nicolette

    2008-12-01

    In Tysiac v. Poland (2007) the Strasbourg Court ruled in favour of the applicant (who had been denied access to a lawful therapeutic abortion), finding that Poland had failed to comply with its positive obligations to safeguard the applicant's right to effective respect for her private life under Article 8. Exploring this controversial judgment, the author assesses the claim that Tysiac marks a 'radical shift' on the part of the Court in creating a 'right to abortion'. The author argues that while Tysiac makes an important addition to abortion jurisprudence, the notion it founds such a 'right' greatly overstates the legal significance of this case.

  16. Testing efficacy of teaching food safety and identifying variables that affect learning in a low-literacy population.

    Science.gov (United States)

    Mosby, Terezie Tolar; Romero, Angélica Lissette Hernández; Linares, Ana Lucía Molina; Challinor, Julia M; Day, Sara W; Caniza, Miguela

    2015-03-01

    Nurses at a meeting of the Asociación de Hemato Oncología Pediátrica de Centroamérica y El Caribe recognized food safety as one of the main issues affecting patient care. The objective was to increase awareness of food safety issues among caregivers for pediatric cancer patients in Guatemala and El Salvador. A low-literacy booklet about food safety, "Alimentación del niño con cáncer (Feeding the child with cancer)," was developed for caregivers. Tests were developed to assess information acquisition and retention. An educator's guide was developed for consistency of education along with a demographics questionnaire. The efficacy of the booklet was tested with 162 caregivers of patients with newly diagnosed leukemia. Information retention was tested 1 and 3 months after the initial education. The booklet was found to be efficient for food safety education. There was no significant difference between post-educational knowledge in either country at 1 month or in Guatemala at 3 months. Pre-educational knowledge was not associated with any demographic variable except for self-reported ability to read in El Salvador. There was no significant association between learning ability and demographic variables in either country. Caregivers from El Salvador had a better ability to learn than caregivers from Guatemala. Education using the booklet greatly improved food safety knowledge, which remained high 1 and 3 months later. Education with the booklet was efficacious for teaching a low-literacy population about food safety. However, it is unknown which part of the education contributed to the significant improvement in knowledge.

  17. Comparative efficacy of antigen and antibody detection tests for human trichinellosis

    Energy Technology Data Exchange (ETDEWEB)

    Ivanoska, D.; Cuperlovic, K.; Gamble, H.R.; Murrell, K.D.

    1989-02-01

    Sera collected from patients with suspected or confirmed exposure to Trichinella spiralis were tested for circulating parasite antigens and antiparasite antibodies. Using an immunoradiometric assay, excretory--secretory antigens from muscle-stage larvae of T. spiralis were detected in the sera of 47% of 62 patients with clinical trichinellosis and 13% of 39 patients without clinical signs but suspected of exposure to infected meat. In comparison, antibodies were detected using an indirect immunofluorescent test in the circulation of 100% of the 62 patients with clinical trichinellosis and 46% of the 39 patients with suspected exposure. The presence of antibodies specific to excretory-secretory products of T. spiralis muscle larvae was confirmed in the majority of the samples tested by a monoclonal antibody-based competitive inhibition assay. These results indicate that antibody detection is a more sensitive diagnostic method for human trichinellosis, but that antigen detection might be a useful confirmatory test because it is a direct demonstration of parasite products in the circulation.

  18. diag ostic efficacy of i direct hemaggluti atio test i relatio to kato ...

    African Journals Online (AJOL)

    user

    exceptions such as the ones used by van Gool et al. (18), most of the previously used IHA test kits were not commercially available for use in epidemiologic application. These previous works have reported sensitivity ranging from 71 to 100% and specificity ranging from 80 to 100%. In the present study, the sensitivity of IHA ...

  19. A Stress Inoculation Program to Cope with Test Anxiety: Differential Efficacy as a Function of Worry or Emotionality

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    Isabel Serrano Pintado

    2016-01-01

    Full Text Available Objective: This study experimentally investigated whether the effects of three different coping programs designed to reduce test anxiety were due to the predominant component of participants’ anxiety. Design: The study involved 259 participants, high text anxiety university students, real clinical cases collected and studied during eight years. The experimental sample was finally composed of 94 selected participants with irrational test anxiety. The experimental factors were: Therapy (intra-subject factor, pre and post- intervention, Treatment (cognitive, physiological and cognitive-physiological, Worry (high-low and Emotionality (high-low. Measures: Several anxiety questionnaires (TAS, TAI, ITA, CI, STAI were used as indicators of anxiety. Results: Using confidence intervals, we found evidence of changes in the level of measured anxiety in varied degree in the different Worry and Emotionality groups. Conclusion: The three different training programmes reduced test anxiety but did not lead to reductions on the same scale in pre-test anxiety in different groups of emotionality and worry. These results could be decisive in the phase of selection of the most suitable treatment for the patient along the therapeutic process.

  20. Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

    Science.gov (United States)

    Marriott, James J; Miyasaki, Janis M; Gronseth, Gary; O'Connor, Paul W

    2010-05-04

    The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a "black box" warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in approximately 12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in approximately 0.4%, and leukemia occurs in approximately 0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking.

  1. [Evaluation of the therapeutic efficacy and safety of the selective anxiolytic afobazole in generalized anxiety disorder and adjustment disorders: Results of a multicenter randomized comparative study of diazepam].

    Science.gov (United States)

    Syunyakov, T S; Neznamov, G G

    to summarize the previously published results of a multicenter randomized clinical research phase III study trial of afobazole (INN: fabomotizole) versus diazepam in the treatment of patients with generalized anxiety disorder (GAD) and adjustment disorders (AD). Five investigating centers included 150 patients aged 18 to 60 years (60 patients with GAD and 90 with AD) a simple structure of anxiety disorders without concurrent mental, neurological or somatic disorders. Patients were randomized to take afobazole (30 mg/day; n=100) or diazepam (30 mg/day; n=50) for 30 days. Prior to drug administration, patients susceptible to placebo were excluded according to the results of its 7-day use. Withdrawal syndrome was evaluated within 10 days after completion of active therapy. The primary efficacy endpoint was the change of Hamilton Anxiety Rating Scale (HAMA) total score. The scores of the Clinical Global Impression (CGI) Scale and the Sheehan Scale as secondary efficacy endpoints  were analyzed. Drug safety was evaluated by assessment of adverse events. Afobazole and diazepam caused a significant reduction of HAMA total score. In the afobazole group, the reduction of anxiety  exceeded that in the diazepam group (the difference in the total score changes was 2.93 [0.67; 5.19]; p=0,01).The proportion of patients with reduction of disease severity was 72% in the afobazole group and 58% in the diazepam group. After therapy completion, the proportion of patients with no or mild disorder in the afobazole group was significantly higher than that in the diazepam group (69 and 44%, respectively; χ2=12.46; p=0,014). There was a trend toward a higher subjective patient-rated estimate of the afobazole effect using the Sheehan scale. There were a total of 15 and 199 adverse events in the afobazole and diazepam groups, respectively. No manifestations of afobazole withdrawal syndrome were found. Diazepam withdrawal syndrome was observed in 34 (68%) patients. Afobazole is an

  2. An indole alkaloid from a tribal folklore inhibits immediate early event in HSV-2 infected cells with therapeutic efficacy in vaginally infected mice.

    Science.gov (United States)

    Bag, Paromita; Ojha, Durbadal; Mukherjee, Hemanta; Halder, Umesh Chandra; Mondal, Supriya; Chandra, Nidhi S; Nandi, Suman; Sharon, Ashoke; Sarkar, Mamta Chawla; Chakrabarti, Sekhar; Chattopadhyay, Debprasad

    2013-01-01

    Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the

  3. Stepwise targeted drug delivery to liver cancer cells for enhanced therapeutic efficacy by galactose-grafted, ultra-pH-sensitive micelles.

    Science.gov (United States)

    Yan, Guoqing; Wang, Jun; Hu, Liefeng; Wang, Xin; Yang, Guanqing; Fu, Shengxiang; Cheng, Xu; Zhang, Panpan; Tang, Rupei

    2017-03-15

    To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7.4; (ii) responding to tumoral extracellular pH following gradually larger nanoparticles (NPs); (iii) conjugating receptors in the cell membrane of liver cancer through surface galactose-ligands of micelles; (iv) being sensitive to tumoral intracellular pH following further swelling for rapid drug release. In vitro cytotoxicity and cellular uptake measurement showed that POEAd-g-LA20-DOX micelle was more easily internalized and more toxic effect on tumor cells than free DOX. Moreover, in vivo biodistribution and tumor inhibition examinations demonstrated that POEAd-g-LA20-DOX formulation had more superior efficacy to significantly enhance drug accumulation in tumor, and then restrain tumor growth while decreasing drug concentration in heart. Chemotherapeutic efficacy is limited by poor tumor selectivity, which also causes severe toxicity in normal tissues and organs, although many targeted drug delivery systems have been developed by passive targeting strategies or active targeting strategies with specific targeting ligands in recent years. Herein, galactose-grafted, ultra-pH-sensitive, ortho ester-based drug carriers, which can respond to both extracellular and intracellular pH, and target to galactose-receptors in cell membrane, have been successfully constructed by facile method

  4. Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test

    Directory of Open Access Journals (Sweden)

    Dhanya N

    2008-01-01

    Full Text Available Background: Histamine is the major mediator of allergic reactions. Newer H1 antihistaminics like levocetirizine, fexofenadine, and desloratadine are used in the treatment of seasonal and perennial allergic rhinitis and urticaria. The ability to block the cutaneous response to intradermal histamine is used to evaluate the potential of antihistamines. Aims: To compare the potency, onset, and duration of action of the commonly used antihistamines-levocetirizine, fexofenadine, and desloratadine Methods: Thirty volunteers were given three single doses of levocetirizine, fexofenadine and desloratadine at weekly intervals. A pretest was performed by using the intradermal histamine prick test. After administration of the drugs, the intradermal test was repeated at ½, 1, 2, 3, 6 and 24 h, and the sizes of the wheal were measured. The mean values were taken and were compared by using Levene′s t-test. Results: At 30 min, fexofenadine showed a statistically significant suppression of wheal size compared to levocetirizine and desloratadine. Two and three hours after administration, levocetirizine and fexofenadine showed statistically significant inhibition of wheal size while only levocetirizine had this effect after six hours when compared to desloratadine. Desloratadine showed greater inhibition of wheal size at the end of 24 h when compared to levocetirizine and fexofenadine but this was not statistically significant. Conclusions: Fexofenadine had the earliest onset of action while levocetirizine showed maximum inhibition of wheal response after three and six hours.

  5. Radioiodination of cyclin dependent kinase inhibitor Olomoucine loaded Fe rate at Au nanoparticle and evaluation of the therapeutic efficacy on cancerous cells

    Energy Technology Data Exchange (ETDEWEB)

    Takan, Gokhan; Guldu, Ozge Kozgus; Medine, Emin Ilker [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2017-06-01

    Magnetic nanoparticles have promising biomedical applications such as drug delivery, novel therapeutics and diagnostic imaging. Magnetic drug delivery combination works on the delivery of magnetic nanoparticles loaded with drug to the target tissue by means of an external magnetic field. Gold coated iron oxide (Fe rate at Au) nanoparticles can provide useful surface chemistry and biological reactivity. Covalent conjugation to the Fe rate at Au nanoparticles through cleavable linkages can be used to deliver drugs to tumor cells, then the drug can be released by an external. In this paper, purine based cyclin dependent kinases (CDKs) inhibitor Olomoucine (Olo) [2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine] was loaded on gold coated iron oxide (Fe rate at Au) nanoparticles and radiolabeled with {sup 131}I to combine magnetic targeted drug delivery and radiotherapy. Fe rate at Au nanoparticles were synthesized by microemulsion method. The characterization of nanoparticles was examined by TEM, VSM and XRD. Amine activation was utilized by cysteamine hydrochloride and then CDI was used for conjugation of Olomoucine. Antiproliferative effect and cytotoxicity of Olomoucine loaded Fe rate at Au nanoparticles (Fe rate at Au-Olo) were investigated on MCF7 and A549 cell lines. Proliferation rate was decreased while uptake of Fe rate at Au-Olo on both cell lines was high in comparison with Olomoucine. Also, enhanced incorporation ratio was observed under external magnetic field.

  6. COMPARATIVE ANALYSIS OF THE THERAPEUTIC EFFICACY OF PROSPIDINE AND CISPLATIN IN NEOADJUVANT INTRAVESICAL CHEMOTHERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    T. I. Shabunina

    2014-07-01

    Full Text Available Objective: to evaluate the antitumor efficiency of the intravesical administration of prospiridine versus cisplatin in the treatment of nonmuscle invasive bladder cancer (NMIBC.Subjects and methods. The therapeutic effect of neoadjuvant intravesical chemotherapy (CT was comparatively analyzed in 74 patients with transitional cell NMIBC. Thirty-four patients were given prospidine in a single dose of 200 mg to the total dose of 4000 mg; 40 patients received cisplatin in a single dose of 20 mg to the total dose of 500 mg.Results. There was a preponderance of moderate dysuretic manifestations (55 % during CH with prospidine and mild cystitis (62.5 % during that with cisplatin. In the prospidine group, mild leukopenia was observed in 5 (14.7 % patients receiving intravesical CT with prospidine and in none patients treated with cisplatin. In the same group, 11.7 and 23.5 % achieved complete or partial regression, respectively. The total effect of intravesical CT with prospidine was 32.4 % and that with cisplatin was 50 % (complete or partial regression was seen in 22.5 and 27.5 %, respectively.Conclusion. The study has demonstrated that intravesical CT with prospidine is effective and well tolerated and may be recommended for the treatment of NMIBC.

  7. Assessment of Safety and Therapeutic Efficacy of Rosa damascena L. and Quercus infectoria on Cardiovascular Performance of Normal and Hyperlipidemic Rabbits: Physiologically Based Approach.

    Science.gov (United States)

    Joukar, Siyavash; Askarzadeh, Masoumeh; Shahouzehi, Beydolah; Najafipour, Hamid; Fathpour, Hossein

    2013-01-01

    According to the use of Quercus infectoria (QI) and Rosa damascena L. (RD) for therapeutic purposes and lack of adequate information about their cardiovascular effects, we investigated the cardiovascular indices of rabbits which chronically pretreated with these agents. Animal groups were control group (CTL), RD and QI groups with normal chow plus 1.5 g RD and QI extracts, respectively, in each kg of the diet for 45 days; Hyperlipidemic (H) group received high-fat diet for 45 days; H+RD and H+QI groups received high fat diet plus QI and RD extracts, respectively. Blood pressure was greater in H+RD group than CTL, RD, and H groups. Left ventricular developed pressure and left ventricular systolic pressure increased significantly in H+RD group versus CTL and RD groups (P < 0.05 and P < 0.0001, resp.) and in H+QI groups (P < 0.01 versus QI groups). Left ventricular end diastolic pressure (LVEDP) showed significant reduction in H+QI group versus H group. QI attenuated the values of total cholesterol, LDL, TG, and atherogenic indices of plasma when coadministrated with a high-fat diet. The results suggest the antilipidemic and antiatherogenic effects of QI. In addition, the use of RD along with a high-fat diet may increase the risk of hypertension in rabbits.

  8. Assessment of Safety and Therapeutic Efficacy of Rosa damascena L. and Quercus infectoria on Cardiovascular Performance of Normal and Hyperlipidemic Rabbits: Physiologically Based Approach

    Directory of Open Access Journals (Sweden)

    Siyavash Joukar

    2013-01-01

    Full Text Available According to the use of Quercus infectoria (QI and Rosa damascena L. (RD for therapeutic purposes and lack of adequate information about their cardiovascular effects, we investigated the cardiovascular indices of rabbits which chronically pretreated with these agents. Animal groups were control group (CTL, RD and QI groups with normal chow plus 1.5 g RD and QI extracts, respectively, in each kg of the diet for 45 days; Hyperlipidemic (H group received high-fat diet for 45 days; H+RD and H+QI groups received high fat diet plus QI and RD extracts, respectively. Blood pressure was greater in H+RD group than CTL, RD, and H groups. Left ventricular developed pressure and left ventricular systolic pressure increased significantly in H+RD group versus CTL and RD groups ( and , resp. and in H+QI groups ( versus QI groups. Left ventricular end diastolic pressure (LVEDP showed significant reduction in H+QI group versus H group. QI attenuated the values of total cholesterol, LDL, TG, and atherogenic indices of plasma when coadministrated with a high-fat diet. The results suggest the antilipidemic and antiatherogenic effects of QI. In addition, the use of RD along with a high-fat diet may increase the risk of hypertension in rabbits.

  9. Comparison of Therapeutic Efficacy and Urodynamic Findings of Solifenacin Succinate versus Mirabegron in Women with Overactive Bladder Syndrome: Results of a Randomized Controlled Study.

    Science.gov (United States)

    Vecchioli Scaldazza, Carlo; Morosetti, Carolina

    2016-01-01

    We assessed clinical and urodynamic effects of solifenacin versus mirabegron in women with overactive bladder (OAB) syndrome. Eighty women with OAB were randomized into 2 groups. In group A, the patients received solifenacin 5 mg once a day for 12 weeks; in group B, the patients received mirabegron 50 mg once a day for 12 weeks. Symptoms were assessed with OAB Symptom Score (OABSS). Patients underwent urodynamic investigation with pressure flow study. OABSS and urodynamic study were performed before and after treatment. Both solifenacin and mirabegron were effective in improving OAB symptoms. Mirabegron showed greater tolerability with fewer patients discontinuing therapy because of side effects. Both solifenacin and mirabegron were effective in improving the storage function in the pressure flow study, but solifenacin showed a significant reduction of the detrusor pressure in the voiding phase with an increase in the postvoid residual urine volume. Mirabegron has shown to be a drug with the better balance between efficacy and tolerability in women with OAB. © 2016 S. Karger AG, Basel.

  10. A review of technology-assisted self-help and minimal contact therapies for drug and alcohol abuse and smoking addiction: is human contact necessary for therapeutic efficacy?

    Science.gov (United States)

    Newman, Michelle G; Szkodny, Lauren E; Llera, Sandra J; Przeworski, Amy

    2011-02-01

    Technology-based self-help and minimal contact therapies have been proposed as effective and low-cost interventions for addictive disorders, such as nicotine, alcohol, and drug abuse and addiction. The present article reviews the literature published before 2010 on computerized treatments for drug and alcohol abuse and dependence and smoking addiction. Treatment studies are examined by disorder as well as amount of therapist contact, ranging from self-administered therapy and predominantly self-help interventions to minimal contact therapy where the therapist is actively involved in treatment but to a lesser degree than traditional therapy and predominantly therapist-administered treatments involving regular contact with a therapist for a typical number of sessions. In the treatment of substance use and abuse it is concluded that self-administered and predominantly self-help computer-based cognitive and behavioral interventions are efficacious, but some therapist contact is important for greater and more sustained reductions in addictive behavior. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-11-17

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

  12. Efficacy of intra-articular hyaluronic acid injections and exercise-based rehabilitation programme, administered as isolated or integrated therapeutic regimens for the treatment of knee osteoarthritis.

    Science.gov (United States)

    Saccomanno, Maristella F; Donati, Fabrizio; Careri, Silvia; Bartoli, Matteo; Severini, Gabriele; Milano, Giuseppe

    2016-05-01

    To assess the efficacy of intra-articular hyaluronic acid (HA