WorldWideScience

Sample records for combined neuroprotective modalities

  1. [Combined-modality therapy for lung cancer].

    Science.gov (United States)

    Miura, Satoru; Yamamoto, Nobuyuki

    2010-06-01

    Lung cancer is treated with surgery, radiotherapy and chemotherapy according to histology and clinical stage. Advanced stage lung cancer patients cannot be cured, but early and locally-advanced stage patients can be cured by intensive combined-modality therapy. Combined-modality therapy with surgery plus adjuvant chemotherapy is standard for resectable IB-IIIA non-small cell lung cancer (NSCLC) and stage I small cell lung cancer (SCLC) patients. Chemoradiotherapy is standard for unresectable locally-advanced NSCLC and limited-stage SCLC patients. Recently, several new drugs, molecular targeted drugs, have become available for clinical use and trials. We reviewed standard and new strategy of combined-modality therapy for early and locally-advanced lung cancer patients.

  2. Seeing double: combined modalities in functional imaging

    Energy Technology Data Exchange (ETDEWEB)

    Del Guerra, A. E-mail: delguerra@pi.infn.it; Damiani, C.; Di Domenico, G.; Gambaccini, M.; Motta, A.; Sabba, N.; Zavattini, G

    2001-09-21

    Various dedicated instruments for combined modalities in functional imaging are being developed by our group: a small animal PET/SPECT scanner, two scintimammography apparatus for breast cancer diagnosis, one with RX/PEM and the other with RX/SPECT capability. The performance and the status of development of these devices will be reported.

  3. Combined modality therapy in the elderly population.

    Science.gov (United States)

    Lin, Lilie L; Hahn, Stephen M

    2009-08-01

    The incidence of cancer among older patients continues to rise. The use of combined modality therapy has improved survival in a variety of malignancies, including rectal, head and neck, and lung cancer; however, the addition of chemotherapy increases substantially the toxicities of treatment. Elderly patients have generally been excluded from prospective clinical trials and as such, there is a lack of evidence-based data with regards to the most appropriate treatment. Age itself should not be used as a criterion for foregoing combined modality therapy in elderly patients. Due to the increased toxicity of therapy, patients must be carefully selected. Any medical intervention should account for life expectancy, performance status, tolerance to therapy, and presence of medical or social conditions that may impact therapy. We encourage a comprehensive geriatric assessment to evaluate functional status, comorbidities, mental status, psychological state, social support, nutritional status, polypharmacy, and geriatric conditions in order to improve a patient's overall functional status during the course of therapy. Fit elderly patients should be considered candidates for combined modality therapy, however, because they are potentially more vulnerable to therapy, careful attention should be paid to hydration and nutritional status with early intervention when necessary. Investigators should be encouraged to expand eligibility to include elderly patients on non age-related clinical trials. Additionally, therapy-related clinical trials directed at the elderly should be developed.

  4. Combined modality treatment in nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Sang Mo [College of Medicine, Catholic Univ., Daegu (Korea, Republic of); Kim, Jae Cheol; Park, In Kyu [College of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)

    2001-06-01

    We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed 32% with llB, 30% with III, and 38% with IV in induction group, and 50%, 33.3%, and 16.7% in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin 100 mg/m{sup 2} was intravenously infused on day 1, and 5-FU 1,000 mg/m{sup 2} on day 2-6. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were 1-3 (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size 1.8-2.0 Gy and 5 fractions/week was done. Total dose was 69.4-86 Gy(median 73.4 Gy) for induction group, and 69.4-75.4 Gy (median 70.8 Gy) for concurrent group. Follow-up time was 9 -116 months (median 40.5 months) for induction group, 14-29 months (median 21 months) for concurrent group, respectively. Overall 2 year survival rate (2YSRj for all patients was 78.7%. According to treatment modality, 2YSR were 77% for induction group, 87% for concurrent group (p>0.05). 2 year disease-free survival rate were 56% and 81% (p>0.05), respectively. Complete response to treatment were 75.5% for induction group and 91.7% for concurrent group, but there was no statistical difference. The incidence of grade 3- 4 hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in

  5. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L; Carde, P; Mauch, P

    1992-01-01

    In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a global...... be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against the use of chemotherapy up front is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may...

  6. Contemporary radiation therapy in combined modality therapy for Hodgkin lymphoma.

    Science.gov (United States)

    Narang, Amol K; Terezakis, Stephanie A

    2015-05-01

    The advent of effective combination chemotherapy markedly changed the management of Hodgkin lymphoma, establishing combined modality therapy as the standard of care for most patients with this disease. In response, significant interest has been shown in refining the delivery of radiation in the combined modality setting such that toxicity is minimized while still preserving disease control. An understanding of the way in which radiation treatment fields, prescription dose, and advanced technology have evolved to accomplish these goals is critical. Moreover, fluency in the clinical literature exploring contemporary questions, such as the omission of radiation and response-based treatment, is equally important. Knowledge of these topics will yield both an appreciation of the value of radiation in the combined modality setting and the ability to better customize treatment regimens to individual patients. Copyright © 2015 by the National Comprehensive Cancer Network.

  7. Biology-based combined-modality radiotherapy: workshop report

    International Nuclear Information System (INIS)

    Mason, Kathryn A.; Komaki, Ritsuko; Cox, James D.; Milas, Luka

    2001-01-01

    Purpose: The purpose of this workshop summary is to provide an overview of preclinical and clinical data on combined-modality radiotherapy. Methods and Materials: The 8th Annual Radiation Workshop at Round Top was held April 13-16, 2000 at the International Festival Institute (Round Top, TX). Results: Presentations by 30 speakers (from Germany, Netherlands, Australia, England, and France along with U.S. participants and M. D. Anderson Cancer Center faculty) formed the framework for discussions on the current status and future perspectives of biology-based combined-modality radiotherapy. Conclusion: Cellular and molecular pathways available for radiation modification by chemical and biologic agents are numerous, providing new opportunities for translational research in radiation oncology and for more effective combined-modality treatment of cancer

  8. Combined modality treatment for stage III ovarian carcinoma

    International Nuclear Information System (INIS)

    Rizel, S.; Biran, S.; Brufman, G.; Sulkes, A.; Weshler, Z.; Fuks, Z.; Anteby, S.O.; Milwidsky, A.

    1985-01-01

    Thirty-eight Stage III ovarian carcinoma patients were treated with a combined modality protocol consisting of sequential initial surgery with a maximal tumor reduction, CHAD combination chemotherapy, second look reductive surgery and whole abdominal irradiation. The authors concluded that their and similar protocols of a sequential multimodal approach to the treatment of Stage III ovarian carcinoma involving aggressive surgery, chemotherapy and radiation are both feasible and safe, but their curative potential for advanced ovarian carcinoma is as yet unknown. (Auth.)

  9. Combining Multi-modal Features for Social Media Analysis

    Science.gov (United States)

    Nikolopoulos, Spiros; Giannakidou, Eirini; Kompatsiaris, Ioannis; Patras, Ioannis; Vakali, Athena

    In this chapter we discuss methods for efficiently modeling the diverse information carried by social media. The problem is viewed as a multi-modal analysis process where specialized techniques are used to overcome the obstacles arising from the heterogeneity of data. Focusing at the optimal combination of low-level features (i.e., early fusion), we present a bio-inspired algorithm for feature selection that weights the features based on their appropriateness to represent a resource. Under the same objective of optimal feature combination we also examine the use of pLSA-based aspect models, as the means to define a latent semantic space where heterogeneous types of information can be effectively combined. Tagged images taken from social sites have been used in the characteristic scenarios of image clustering and retrieval, to demonstrate the benefits of multi-modal analysis in social media.

  10. Survival Outcomes for Combined Modality Therapy for Sinonasal Undifferentiated Carcinoma.

    Science.gov (United States)

    Kuo, Phoebe; Manes, R Peter; Schwam, Zachary G; Judson, Benjamin L

    2017-01-01

    Objective Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy of the nasal cavity and paranasal sinuses. Multi-institutional studies examining outcomes of combined modality treatment versus other treatment modalities have not been performed. The objective of our study was to present outcomes for multimodality therapy through use of the National Cancer Database. Study Design Retrospective cohort study. Setting National Cancer Database. Methods A total of 435 cases of SNUC diagnosed between 2004 and 2012 were identified. Kaplan-Meier analyses were performed to find 5-year cumulative survival rates. Multivariate Cox regression evaluated overall survival based on treatment when adjusting for other prognostic factors (age, primary site, sex, race, comorbidity, insurance, and TNM stage). Within the surgery + chemoradiotherapy group, survival analysis was also performed to compare outcomes for induction and adjuvant chemotherapy. Results The cumulative 5-year survival rate was 41.5%, and 36.1% of patients received surgery with chemoradiotherapy. In multivariate analysis, surgery + chemoradiotherapy was associated with significantly improved overall survival versus surgery + radiotherapy and radiotherapy but not significantly different from chemoradiotherapy. Within the surgery + chemoradiotherapy group, induction and adjuvant chemotherapy groups did not have associated differences in survival. Conclusion Combined modality therapy (chemoradiotherapy or surgery + chemoradiotherapy) is associated with improved survival outcomes versus other treatment modalities in patients with sinonasal undifferentiated carcinoma.

  11. Prostatic Leiomyosarcoma: The Case for Combined Modality Therapy

    OpenAIRE

    El-Sharkawi, Salah; Vaughton, Keith

    1997-01-01

    Patient. A 65-year old man who had previously undergone surgery for benign prostatic hyperplasia presented with symptoms of recurrent bladder outflow obstruction. Cystoscopy revealed the presence of recurrent tissue. Results. Histology identified a leiomyosarcoma. Several years after further surgery and radiotherapy, the patient presented with secondaries in the lungs and brain, but there was no evidence of local recurrence. Discussion. It is suggested that combined modality therapy (conserva...

  12. The generalized algebraic modal combination (GAC) rule validation program

    International Nuclear Information System (INIS)

    Mertens, P.G.; Culot, M.V.; Sahgal, S.; Tinic, S.

    1991-01-01

    With R.G. 1.92 the NRC imposes to use the absolute values of the modal responses when performing Response Spectra modal combination with coupling factors derived from the current heuristic, stationary or pseudo-stationary random vibration models. This results in overly conservative calculations in the case of closely spaced modes of opposite signs, a case frequently encountered in dynamic analyses in particular when systems with close modal frequencies have a small mass ratio. A new generalised algebraic combination (GAC) formula and its associated coupling factor have been theoretically derived by the first author. It is based on a non-stationary, non-white noise random vibration model which fully accounts for all the time and frequency dependent aspects of the time histories. This should allow the conservative use of algebraic signs in the modal combination over the whole frequency range, and allow a derogation to the current NRC R.G. 1.92 practice to use absolute signs. The use of the industry wide accepted RS method with the GAC rule will result in more economical and safer NPPs through the reduction of an excessive and unrealistic number of seismic restraints and avoidance of prematurely fatigued plants. It is envisaged to use the GAC seismic response combination method for the evaluation of the seismic response of auxiliary class one lines attached to the primary coolant loop piping of the Beznau 1 and 2 nuclear power plants. Since the plant is in operation, it is imperative to use a methodology which is conservative but still as realistic as possible. The paper presents an introduction to the GAC rule and some aspects of the validation program, which will jointly be undertaken by WESI and NOK for obtaining acceptance by the Swiss Safety Authorities for a seismic qualification program. (author)

  13. Photodynamic Therapy and Its Role in Combined Modality Anticancer Treatment.

    Science.gov (United States)

    Brodin, N Patrik; Guha, Chandan; Tomé, Wolfgang A

    2015-08-01

    Photodynamic therapy (PDT) is a relatively new modality for anticancer treatment and although the interest has increased greatly in the recent years, it is still far from clinical routine. As PDT consists of administering a nontoxic photosensitizing chemical and subsequently illuminating the tumor with visible light, the treatment is not subject to dose-limiting toxicity, which is the case for established anticancer treatments like radiation therapy or chemotherapy. This makes PDT an attractive adjuvant therapy in a combined modality treatment regimen, as PDT provides an antitumor immune response through its ability to elicit the release of damage-associated molecular patterns and tumor antigens, thus providing an increased antitumor efficacy, potentially without increasing the risk of treatment-related toxicity. There is great interest in the elicited immune response after PDT and the potential of combining PDT with other forms of treatment to provide potent antitumor vaccines. This review summarizes recent studies investigating PDT as part of combined modality treatment, hopefully providing an accessible overview of the current knowledge that may act as a basis for new ideas or systematic evaluations of already promising results. © The Author(s) 2014.

  14. Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments.

    Science.gov (United States)

    Hernández, María; Urcola, J Haritz; Vecino, Elena

    2008-05-01

    The aim of the present study is to evaluate the neuroprotective effect of two antiglaucomatous substances, regardless of their hypotensive effect in the eye. Brimonidine, which does not reduce IOP when administered intraperitoneally, and latanoprost, which has a renowned hypotensive effect topically. We examined rat retinal ganglion cell (RGC) survival and size distribution in experimental glaucoma in response to different glaucomatous agents. IOP was elevated by episcleral vein cauterization (EVC) prior to the application of different treatments: (I) PBS application (control group), (II) intraperitoneal administration of brimonidine (a general hypotensive agent), (III) topical application of latanoprost (an ocular hypotensive agent), and (IV) latanoprost combined with brimonidine. After 12 weeks, RGCs were retrogradely labeled with fluorogold and RGC density was analyzed. EVC caused a significant increase (42%) in IOP in each group before drug treatment. After 12weeks of EVC, RGC survival in control vs. EVC rats was 78.9+/-3.2%. No IOP reduction was observed in brimonidine injected rats, but RGC survival at 12 weeks was total (103.7+/-2.7%). In latanoprost treated rats, IOP dropped by around 22% and 94.7+/-3.7% of the RGC population survived. Finally in the latanoprost+brimonidine combined group, IOP was significantly reduced by 25% and 94.4+/-2.2% of RGCs survived. Surprisingly, whereas EVC led to a 6% increase in RGC soma size, brimonidine treatment was associated with a 9% reduction in the soma size of RGCs at 12 weeks. We conclude that brimonidine exerts a neuroprotective effect via a mechanism which is independent of IOP reduction. These findings indicate that cell survival in glaucoma may be enhanced by neuroprotective strategies which are independent of IOP reduction. No synergistic neuroprotective effect was observed when both treatments were applied simultaneously.

  15. Modality

    DEFF Research Database (Denmark)

    Klinge, Alex; Müller, Henrik Høeg

    Modality: Studies in Form and Function reflects the diversity of theoretical frameworks and the heterogeneity of linguistic phenomena under the general heading of modality. Researchers in the fields of logic, philosophy and linguistics have for many years been pondering the elusive nature of moda...... in discourse. This volume raises new questions and offers re-examination of known phenomena which should provide interesting reading to linguists and students of linguistics of all theoretical persuasions.......Modality: Studies in Form and Function reflects the diversity of theoretical frameworks and the heterogeneity of linguistic phenomena under the general heading of modality. Researchers in the fields of logic, philosophy and linguistics have for many years been pondering the elusive nature...... of modality and grappled with ways of capturing it. The 11 studies included here cover the span from contributions that seek to clarify controversial theoretical constructs to studies which take an empirical approach to linguistic categories and cross-linguistic typological issues. The key concepts addressed...

  16. [Combined modality therapy for a patient with primary adrenal lymphoma].

    Science.gov (United States)

    Matsuno, Teppei; Kuroda, Hiroyuki; Jomen, Wataru; Yoshida, Masahiro; Yamada, Michiko; Sato, Masanori; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Nojiri, Shuichi; Arihara, Yohei; Kato, Junji

    2014-04-01

    A 71-year-old man with malaise, anorexia, and weight loss was referred to our hospital from a clinic. Abdominal computed tomography(CT)revealed bilateral adrenal masses. An ultrasound-guided percutaneous needle biopsy of the adrenal grand indicated diffuse large B-cell lymphoma. A rapid adrenocorticotropic hormone(ACTH)test revealed primary adrenal failure. Rituximab-cyclophosphamide/doxorubicin/vincristine/prednisolone(common name, R-CHOP)therapy accompanied by intrathecal treatment was initiated along with steroid replacement therapy. After the fourth courses, a CT scan showed a reduction of the adrenal masses, and there was no[18F]-fluorodeoxyglucose(FDG)uptake in the adrenal masses. The patient has remained in metabolic complete remission. Subsequently, both adrenal lymphomas were irradiated. The patient has been disease-free for 6 months after the diagnosis of primary adrenal lymphoma. The combined modality of chemoradiation therapy plus intrathecal treatment could be effective for primary adrenal lymphoma with a poor prognosis.

  17. Modality

    DEFF Research Database (Denmark)

    Klinge, Alex; Müller, Henrik Høeg

    Modality: Studies in Form and Function reflects the diversity of theoretical frameworks and the heterogeneity of linguistic phenomena under the general heading of modality. Researchers in the fields of logic, philosophy and linguistics have for many years been pondering the elusive nature of moda...... in discourse. This volume raises new questions and offers re-examination of known phenomena which should provide interesting reading to linguists and students of linguistics of all theoretical persuasions....

  18. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2016-01-01

    Full Text Available Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days, or combined with acupuncture at Shenting (DU24, Tianzhu (BL10, Sishencong (Extra, Yintang (Extra, Renzhong (DU26, Neiguan (PC6, Shenmen (HT7, Fengchi (GB20, Wangu (GB12 and Baihui (DU20 (once a day for 56 days. Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  19. A Combination of Modal Synthesis and Subspace Iteration for an Efficient Algorithm for Modal Analysis within a FE-Code

    Directory of Open Access Journals (Sweden)

    M.W. Zehn

    2003-01-01

    Full Text Available Various well-known modal synthesis methods exist in the literature, which are all based upon certain assumptions for the relation of generalised modal co-ordinates with internal modal co-ordinates. If employed in a dynamical FE substructure/superelement technique the generalised modal co-ordinates are represented by the master degrees of freedom (DOF of the master nodes of the substructure. To conduct FE modal analysis the modal synthesis method can be integrated to reduce the number of necessary master nodes or to ease the process of defining additional master points within the structure. The paper presents such a combined method, which can be integrated very efficiently and seamless into a special subspace eigenvalue problem solver with no need to alter the FE system matrices within the FE code. Accordingly, the merits of using the new algorithm are the easy implementation into a FE code, the less effort to carry out modal synthesis, and the versatility in dealing with superelements. The paper presents examples to illustrate the proper work of the algorithm proposed.

  20. Combining Different Modalities for 3D Imaging of Biological Objects

    CERN Document Server

    Tsyganov, E; Kulkarni, P; Mason, R; Parkey, R; Seliuonine, S; Shay, J; Soesbe, T; Zhezher, V; Zinchenko, A I

    2005-01-01

    A resolution enhanced NaI(Tl)-scintillator micro-SPECT device using pinhole collimator geometry has been built and tested with small animals. This device was constructed based on a depth-of-interaction measurement using a thick scintillator crystal and a position sensitive PMT to measure depth-dependent scintillator light profiles. Such a measurement eliminates the parallax error that degrades the high spatial resolution required for small animal imaging. This novel technique for 3D gamma-ray detection was incorporated into the micro-SPECT device and tested with a $^{57}$Co source and $^{98m}$Tc-MDP injected in mice body. To further enhance the investigating power of the tomographic imaging different imaging modalities can be combined. In particular, as proposed and shown in this paper, the optical imaging permits a 3D reconstruction of the animal's skin surface thus improving visualization and making possible depth-dependent corrections, necessary for bioluminescence 3D reconstruction in biological objects. ...

  1. [Application of precise radiotherapy in the combined modality therapy of gastrointestinal tract tumors].

    Science.gov (United States)

    Yu, Jin-ming; Meng, Xiang-jiao

    2013-06-01

    Single modality treatment of advanced gastrointestinal cancer has been associated with unfavorable outcomes. Radiotherapy as an important component of the combined modality therapy of gastrointestinal tract tumors may achieve down-staging, increase resection rate while preserving sphincter function, decrease local recurrence rate, and improve survival rate. Precision radiotherapy has better conformity, accuracy, and lower toxicity. Precision radiotherapy will become more and more important in the combined modality therapy of gastrointestinal tract cancer.

  2. Aims of combined modality therapy in rectal cancer (M0).

    Science.gov (United States)

    Gerard, J P; Benezery, K; Doyen, J; Francois, E

    2014-01-01

    OPTIMIZING THE COST/BENEFIT RATIO OF TREATMENT: Evidence Based The aim of a cancer treatment is always to achieve the maximum of cure rate with a minimum of toxicity and best quality of life at an acceptable cost for the society. It is always a multifactorial challenge depending on the patient, the tumor, the doctor, and the society cultural and financial backgrounds. The goal is to find the best cost/benefit ratio between all possible strategies in agreement with a well-informed patient. In rectal cancer (M0) surgery is the cornerstone of treatment. Combined modality therapies aim at optimizing the cost/benefit ratio of possible strategies and only randomized trials can bring strong evidence regarding their results and recommendations. LESSONS FROM RANDOMIZED TRIALS: quite modest During the past decades many phase III trials have shown that: (1) neoadjuvant treatment even with "TME" surgery was better than adjuvant, (2) chemoradiotherapy (CRT) was better than RT alone, (3) long course CRT was probably more efficient (in terms of ypCR) than short course (25/5), and (4) capecitabine was as efficient as 5 FU but oxaliplatin was not adding benefit. Overall, the gains of nCRT remain modest and it is mainly a reduction in local relapse not exceeding 5 %, but no benefit in survival and neither in sphincter saving surgery has been proven. The way forwards organ preservation in case of CCR. Local control: can probably be improved for T4 tumors by RT dose escalation. Survival: can be increased by innovative medical treatment either before or after surgery. may be reduced by a less aggressive treatment in elderly. Conservative treatment: A new field of clinical research is to achieve "organ preservation" (and not only sphincter saving). To modify the surgical approach and preserve the whole rectum, neoadjuvant treatment must achieve safely a clinical complete response. As rectal adenocarcinoma is a relatively radioresistant tumor endocavitary irradiation (contact X-Ray) is a

  3. Biomedical imaging modality classification using combined visual features and textual terms.

    Science.gov (United States)

    Han, Xian-Hua; Chen, Yen-Wei

    2011-01-01

    We describe an approach for the automatic modality classification in medical image retrieval task of the 2010 CLEF cross-language image retrieval campaign (ImageCLEF). This paper is focused on the process of feature extraction from medical images and fuses the different extracted visual features and textual feature for modality classification. To extract visual features from the images, we used histogram descriptor of edge, gray, or color intensity and block-based variation as global features and SIFT histogram as local feature. For textual feature of image representation, the binary histogram of some predefined vocabulary words from image captions is used. Then, we combine the different features using normalized kernel functions for SVM classification. Furthermore, for some easy misclassified modality pairs such as CT and MR or PET and NM modalities, a local classifier is used for distinguishing samples in the pair modality to improve performance. The proposed strategy is evaluated with the provided modality dataset by ImageCLEF 2010.

  4. Combined modality therapy in pancreatic adenocarcinoma: review and updates on a controversial issue.

    Science.gov (United States)

    Cavalcante, Ludimila; Kelsen, David P; Yu, Kenneth H

    2014-01-01

    Due to its extremely high mortality rates, strong efforts continue to be made to develop new therapies in the treatment of pancreatic adenocarcinoma. The use of combined modality chemoradiotherapy for the treatment of pancreatic adenocarcinoma remains an approach with both promise and controversy. This article reviews the conflicting data with regards to role of combined modality therapy in pancreatic adenocarcinoma and provides an update on current studies in the field.

  5. Biomedical Imaging Modality Classification Using Combined Visual Features and Textual Terms

    Directory of Open Access Journals (Sweden)

    Xian-Hua Han

    2011-01-01

    extraction from medical images and fuses the different extracted visual features and textual feature for modality classification. To extract visual features from the images, we used histogram descriptor of edge, gray, or color intensity and block-based variation as global features and SIFT histogram as local feature. For textual feature of image representation, the binary histogram of some predefined vocabulary words from image captions is used. Then, we combine the different features using normalized kernel functions for SVM classification. Furthermore, for some easy misclassified modality pairs such as CT and MR or PET and NM modalities, a local classifier is used for distinguishing samples in the pair modality to improve performance. The proposed strategy is evaluated with the provided modality dataset by ImageCLEF 2010.

  6. Issues of controversy in radiation therapy and combined modality approaches to Hodgkin's disease

    International Nuclear Information System (INIS)

    Greenberger, J.S.; Come, S.E.; Weichselbaum, R.R.

    1979-01-01

    In this article, the issues of controversy in radiation therapy and combined (radiation and chemotherapy) modality treatment in patients with Hodgkin's disease are discussed. These issues included the technical considerations in the radiation therapy of pathological stage IA and IIA Hodgkin's disease; the approach to the patient with clinical stages I or II disease and B symptoms; the management of stage IIIA disease; the approach to the use of combined modality treatment; the management of stages IIIB and IV disease; the management of relapse after radiation or combined modality treatment; the role of staging laparotomy and its relationship to clinical stage and therapeutic approach. It was concluded that improvements in the treatment of Hodgkin's disease permit approximately half of patients to achieve prolonged disease-free survival. However, since there is no stage of the disease for which therapy is invariably successful, new clinical trials, based on prior therapeutic results and patterns of relapse, are justified. While combinations of radiation and chemotherapy may prove more effective than either modality alone, the short- and long-term treatment complications in combined modality approaches must be considered. Further, it appears that significant numbers of patients can be permanently salvaged following relapse from initial treatment. (author)

  7. Targeted radionuclide therapy in combined-modality regimens.

    Science.gov (United States)

    Gill, Martin R; Falzone, Nadia; Du, Yong; Vallis, Katherine A

    2017-07-01

    Targeted radionuclide therapy (TRT) is a branch of cancer medicine concerned with the use of radioisotopes, radiolabelled molecules, nanoparticles, or microparticles that either naturally accumulate in or are designed to target tumours. TRT combines the specificity of molecular and sometimes physical targeting with the potent cytotoxicity of ionising radiation. Targeting vectors for TRT include antibodies, antibody fragments, proteins, peptides, and small molecules. The diversity of available carrier molecules, together with the large panel of suitable radioisotopes with unique physicochemical properties, allows vector-radionuclide pairings to be matched to the molecular, pathological, and physical characteristics of a tumour. Some pairings are designed for dual therapeutic and diagnostic applications. Use of TRT is increasing with the adoption into practice of radium-223 dichloride for the treatment of bone metastases and with the ongoing clinical development of, among others, 177 Lu-dodecanetetraacetic acid tyrosine-3-octreotate (DOTATATE) for the treatment of neuroendocrine tumours and 90 Y-microspheres for the treatment of hepatic tumours. The increasing use of TRT raises the question of how best to integrate TRT into multimodality protocols. Achievements in this area and the future prospects of TRT are evaluated in this Review. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice.

    Science.gov (United States)

    Zhou, Ziqi; Lin, Yanzhu; Zheng, Hongyi; He, Yuzhong; Xu, Haohua; Zhang, Siheng; Weng, Wen; Li, Wei; Zhu, Linyan; Yang, Haifeng

    2015-08-01

    Phenytoin (PHT) is a commonly prescribed first-line antiepileptic drug. However, long-term administration of PHT can cause memory loss and balance disturbance. Gastrodin (GD) is the major bioactive component in Tianma and has sedative, anticonvulsive, memory strengthening, and neuroprotective effects. To combine the two drugs seems attractive; however, little was known about the efficacy of combination therapy. In this study, convulsive attack was successfully induced by penicillin. Isobolographic analysis, memory and balance behavior test, histopathological examination, and Western blot analysis were used to investigate whether the combination therapy of GD and PHT can enhance anticonvulsive effect and reduce the side effects associated with PHT. The GD alone (950.60 mg/kg) and the PHT alone (45.50 mg/kg) could produce an anticonvulsive effect, while comparable effect could be produced by PHT : GD = 1 : 50 (8.59 : 429.27 mg/kg), which reduce the dose of PHT by 81% and GD by 55%. After the chronic anticonvulsive experiments of 16 days, the balance disturbance and short-/long-term memory loss were observed in the PHT group, while the PHT + GD therapy can protect the normal balance and memory function. The neuron morphology of hippocampus was preserved, and the number of surviving neurons after combination therapy was more than the model group. The amount of NF-κB (p65) expression was increased in combination group. All above suggested the potential of the combination of PHT and GD enhances the anticonvulsive effect and the neuroprotective effect and reduces the PHT-associated memory and balance disturbance. The PHT + GD strategy would provide new possibilities as a novel promising methodology to treat epileptic patients. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  9. Neuroprotective and Memory-Enhancing Effect of the Combined Extract of Purple Waxy Corn Cob and Pandan in Ovariectomized Rats.

    Science.gov (United States)

    Kirisattayakul, Woranan; Wattanathorn, Jintanaporn; Iamsaard, Sittichai; Jittiwat, Jinatta; Suriharn, Bhalang; Lertrat, Kamol

    2017-01-01

    The neuroprotectant and memory enhancer supplement for menopause is required due to the side effects of hormone replacement therapy. Since purple waxy corn cob and pandan leaves exert antioxidant and acetylcholinesterase inhibition (AChEI) effects, we hypothesized that the combined extract of both plants (PCP) might provide synergistic effect leading to the improved brain damage and memory impairment in experimental menopause. To test this hypothesis, female Wistar rats were ovariectomized bilaterally and orally given various doses of the functional drink at doses of 20, 40, and 80 mg/kg for 28 days. The animals were assessed nonspatial memory using object recognition test every 7 days throughout the study period. At the end of study, they were assessed with oxidative stress status, AChEI, neuron density, and ERK1/2 signal in the prefrontal cortex (PFC). Interestingly, all doses of PCP increased object recognition memory and neuron density but decreased oxidative stress status in PFC. Low dose of PCP also decreased AChE activity while medium dose of PCP increased phosphorylation of ERK1/2 in PFC. Therefore, the improved oxidative stress status and cholinergic function together with signal transduction via ERK in PFC might be responsible for the neuroprotective and memory-enhancing effects of PCP.

  10. Neuroprotective and Memory-Enhancing Effect of the Combined Extract of Purple Waxy Corn Cob and Pandan in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2017-01-01

    Full Text Available The neuroprotectant and memory enhancer supplement for menopause is required due to the side effects of hormone replacement therapy. Since purple waxy corn cob and pandan leaves exert antioxidant and acetylcholinesterase inhibition (AChEI effects, we hypothesized that the combined extract of both plants (PCP might provide synergistic effect leading to the improved brain damage and memory impairment in experimental menopause. To test this hypothesis, female Wistar rats were ovariectomized bilaterally and orally given various doses of the functional drink at doses of 20, 40, and 80 mg/kg for 28 days. The animals were assessed nonspatial memory using object recognition test every 7 days throughout the study period. At the end of study, they were assessed with oxidative stress status, AChEI, neuron density, and ERK1/2 signal in the prefrontal cortex (PFC. Interestingly, all doses of PCP increased object recognition memory and neuron density but decreased oxidative stress status in PFC. Low dose of PCP also decreased AChE activity while medium dose of PCP increased phosphorylation of ERK1/2 in PFC. Therefore, the improved oxidative stress status and cholinergic function together with signal transduction via ERK in PFC might be responsible for the neuroprotective and memory-enhancing effects of PCP.

  11. A comparison of the neuroprotective efficacy of individual oxime (HI-6) and combinations of oximes (HI-6+trimedoxime, HI-6+K203) in soman-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Tesarova, Sandra

    2011-07-01

    The ability of two combinations of oximes (HI-6+trimedoxime, HI-6+K203) to reduce soman-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of the oxime HI-6 alone, using a functional observational battery. Soman-induced neurotoxicity and the neuroprotective effects of HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with soman at a sublethal dose (90 μg/kg intramuscularly, i.m.; 80% of LD₅₀ value) were monitored by the functional observational battery at 24 hours following soman administration. The results indicate that both tested oxime mixtures combined with atropine were able to allow soman-poisoned rats to survive 24 hours following soman challenge, while 4 nontreated soman-poisoned rats and 1 soman-poisoned rat treated with oxime HI-6 alone combined with atropine died within 24 hours following soman poisoning. While the oxime HI-6 alone combined with atropine treatment was able to eliminate a few soman-induced neurotoxic signs and symptoms, both oxime mixtures showed higher neuroprotective efficacy in soman-poisoned rats. Especially, the combination of HI-6 with trimedoxime was able to eliminate most soman-induced neurotoxic signs and symptoms and markedly reduce acute neurotoxicity of soman in rats. Thus, both tested mixtures of oximes combined with atropine were able to increase the neuroprotective effectiveness of antidotal treatment of acute soman poisonings, compared to the individual oxime.

  12. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    International Nuclear Information System (INIS)

    Dhote, Franck; Carpentier, Pierre; Barbier, Laure; Peinnequin, André; Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie

    2012-01-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  13. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dhote, Franck, E-mail: franck.dhote@irba.fr [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Carpentier, Pierre; Barbier, Laure [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Peinnequin, André [Département Effets biologiques des rayonnements, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); and others

    2012-03-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  14. [Survival of newly diagnosed malignant glioma patients on combined modality therapy].

    Science.gov (United States)

    Yang, Qun-ying; Shen, Dong; Sai, Ke; Jiang, Xiao-bing; Ke, Chao; Zhang, Xiang-heng; Mou, Yong-gao; Chen, Zhong-ping

    2013-01-01

    To explore the survival of newly diagnosed malignant gliomas patients on combined modality therapy of surgery, radiotherapy and chemotherapy. The data of 122 newly diagnosed malignant glioma patients on combined modality therapy at our center between 2000 and 2010 were retrospectively reviewed and analyzed. The median age was 40 years old (range: 5 - 75) and median Karnofsky performance status score (KPS) 80 (range: 60 - 100). Combined modality therapy consisted of surgery (maximal safety tumor resection), followed by fractionated focal irradiation for a total dose of 54 - 60 Gy and then 4 - 6 cycles of adjuvant chemotherapy including temozolomide or nitrosourea-based regimens or other ones without temozolomide and nitrosourea. The overall and progression-free survivals were analyzed by the Kaplan-Meier method and the influencing factors screened by Cox proportional hazard model. There were grade IV (n = 70) and grade III (n = 52). The median survival periods were 17.0 months for grade IV patients and 36.0 months for grade III ones. The 2, 3, 4 and 5-year survival rates were 32.0% vs 64.8%, 19.6% vs 47.8%, 11.8% vs 32.0% and 5.9% vs 25.4% (P Combined modality therapy of surgery, adjuvant radiotherapy and chemotherapy may improve the survival of patients with malignant gliomas.

  15. The Case for Combined-Modality Therapy for Limited-Stage Hodgkin's Disease

    OpenAIRE

    Hill-Kayser, Christine E.; Plastaras, John P.; Tochner, Zelig; Glatstein, Eli

    2012-01-01

    Results of the Hodgkin's Disease.6 trial are critically examined in light of the advances in radiation therapy techniques that have occurred since it was initiated. The ultimate findings of the HD.6 trial do not close the case for combined-modality treatment of limited-stage Hodgkin's disease.

  16. Ultrasmall Biocompatible WO3- x Nanodots for Multi-Modality Imaging and Combined Therapy of Cancers.

    Science.gov (United States)

    Wen, Ling; Chen, Ling; Zheng, Shimin; Zeng, Jianfeng; Duan, Guangxin; Wang, Yong; Wang, Guanglin; Chai, Zhifang; Li, Zhen; Gao, Mingyuan

    2016-07-01

    Ultrasmall biocompatible WO3 - x nanodots with an outstanding X-ray radiation sensitization effect are prepared, and demonstrated to be applicable for multi-modality tumor imaging through computed tomography and photoacoustic imaging (PAI), and effective cancer treatment combining both photothermal therapy and radiation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer.

    Science.gov (United States)

    Kohara, Hiroyuki; Miyauchi, Takako; Suehiro, Yoko; Ueoka, Hiroshi; Takeyama, Hiroyasu; Morita, Tatsuya

    2004-12-01

    Fatigue is one of the most distressful symptoms experienced by patients with advanced cancer. Aromatherapy, footsoak, and reflexology are popular health care modality treatments in Japan, however, the effectiveness of each treatment for cancer-related fatigue has not been fully established. To investigate the effectiveness of combined modality treatment consisting of aromatherapy, footsoak, and reflexology against fatigue, an open study was performed in 20 terminally ill patients with cancer. After a patch test was performed, patients received aromatherapy that was accompanied with footsoak in warm water containing lavender essential oil for 3 minutes, followed by reflexology treatment with jojoba oil containing lavender for 10 min. Fatigue was evaluated using the Cancer Fatigue Scale (CFS) before, 1 hour after, and 4 hours after treatment. Total CFS scores improved significantly after this treatment (from 25.6 +/- 11.0 to 18.1 +/- 10.0, p < 0.001). Among three CFS subscales, physical and cognitive subscale scores were reduced significantly (11.3 +/- 6.1 to 6.7 +/- 6.1, p < 0.001; 4.5 +/- 3.2 to 2.4 +/- 2.4, p < 0.001). No adverse effects were experienced. Because all patients desired to continue this treatment, they received treatment eight times on average. Combined modality treatment consisting of aromatherapy, footsoak, and reflexology appears to be effective for alleviating fatigue in terminally ill cancer patients. To confirm safety and effectiveness of this combined modality treatment, further investigation including randomized treatment assignment is warranted.

  18. Combining motor imagery with selective sensation toward a hybrid-modality BCI.

    Science.gov (United States)

    Yao, Lin; Meng, Jianjun; Zhang, Dingguo; Sheng, Xinjun; Zhu, Xiangyang

    2014-08-01

    A hybrid modality brain-computer interface (BCI) is proposed in this paper, which combines motor imagery with selective sensation to enhance the discrimination between left and right mental tasks, e.g., the classification between left/ right stimulation sensation and right/ left motor imagery. In this paradigm, wearable vibrotactile rings are used to stimulate both the skin on both wrists. Subjects are required to perform the mental tasks according to the randomly presented cues (i.e., left hand motor imagery, right hand motor imagery, left stimulation sensation or right stimulation sensation). Two-way ANOVA statistical analysis showed a significant group effect (F (2,20) = 7.17, p = 0.0045), and the Benferroni-corrected multiple comparison test (with α = 0.05) showed that the hybrid modality group is 11.13% higher on average than the motor imagery group, and 10.45% higher than the selective sensation group. The hybrid modality experiment exhibits potentially wider spread usage within ten subjects crossed 70% accuracy, followed by four subjects in motor imagery and five subjects in selective sensation. Six subjects showed statistically significant improvement ( Benferroni-corrected) in hybrid modality in comparison with both motor imagery and selective sensation. Furthermore, among subjects having difficulties in both motor imagery and selective sensation, the hybrid modality improves their performance to 90% accuracy. The proposed hybrid modality BCI has demonstrated clear benefits for those poorly performing BCI users. Not only does the requirement of motor and sensory anticipation in this hybrid modality provide basic function of BCI for communication and control, it also has the potential for enhancing the rehabilitation during motor recovery.

  19. Neuroprotective effect of combining tanshinone IIA with low-dose methylprednisolone following acute spinal cord injury in rats.

    Science.gov (United States)

    Yao, Nian-Wei; Lu, Yuan; Shi, Li-Qi; Xu, Feng; Cai, Xian-Hua

    2017-05-01

    The present study compared the potential neuroprotective effect of tanshinone IIA (TIIA) monotherapy, methylprednisolone (MP) monotherapy and combined treatment in an adult acute spinal cord injury (ASCI) rat model. The current study used the weight-drop method (Allen's Impactor) in the rat model and the mechanical scratch method in primary spinal cord neuron culture to determine whether the combined treatment was able to reduce the required dosage of MP in the treatment of ASCI to produce a similar or improved therapeutic effect. In vivo male Sprague Dawley rats (n=60) were randomly divided into 5 groups, of which 12 rats were selected for the sham group and T9-T11 laminectomies, leading to ASCI, were performed on 48 of the 60 rats using a 10 g ×25 mm weight-drop at the level of T10 spinal cord. Therefore, the ASCI group (n=12) included the 'laminectomy and weight-drop'. The remaining 36 ASCI model animals were subdivided into 3 groups (n=12 each group): TIIA group (30 mg/kg/day), MP group (30 mg/kg) and combined treatment group (TIIA 30 mg/kg/day + MP 20 mg/kg). Neuronal function following ASCI was evaluated using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Levels of the anti-apoptotic factor B-cell lymphoma-2 (Bcl-2), the pro-apoptotic factors Bcl-2 associated protein X (Bax) and caspase-3, and the inflammatory associated factor nuclear factor-κB, were analyzed by western blot analysis. Immunohistochemistry was used to detect caspase-3. To investigate the underlying mechanism, the anti-oxidative effect of combination TIIA and MP treatment was assessed by measuring the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) in ASCI. In agreement with the experiment in vivo , primary neurons were prepared from the spinal cord of one-day-old Sprague-Dawley rats' and co-cultured with astrocytes from the brain cortex. The injury of neurons was induced by mechanical scratch and levels of apoptosis factors were analyzed by western blot analysis

  20. Risk-based combined-modality therapy of pediatric Hodgkin's lymphoma: a retrospective study.

    Science.gov (United States)

    Ali, Amany; Sayed, Heba; Farrag, Ahmed; El-Sayed, Mohamed

    2010-11-01

    We conducted a retrospective analysis to investigate the clinical outcome of combined-modality therapy using multiagent chemotherapy and involved-field radiotherapy in treatment of children with Hodgkin's lymphoma. Fifty eight cases with newly diagnosed Hodgkin's lymphoma were analyzed. The median follow-up duration was 46 months (range 3-72 months). The 4-year overall and event-free survival rates were 91.5% and 69.7% respectively. High-risk disease (stage IIIB and IV), presence of B symptoms, lymphocyte depletion subtype, bulky disease and late response to chemotherapy were poor prognostic factors. Stage-adapted combined-modality therapy resulted in satisfactory outcome in treatment of pediatric Hodgkin's lymphoma. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Antioxidant activity of dorzolamide/timolol fixed combination in neuroprotective therapy in glaucoma

    Directory of Open Access Journals (Sweden)

    N. I. Kurysheva

    2012-01-01

    Full Text Available Purpose: to study the antioxidant activity of carbonic anhydrase inhibitors and timolol fixed combinations and to compare it with other fixed combinations.Methods: Antioxidant activity (AOA of dorzolamide/timolol (Cosopt, dorzolamide/timolol (Dorzopt Plus, latanoprost/timolol, brimonidine/timolol, travoprost/timolol and bimatoprost/timolol fixed combinations was measured in vitro using the model of oxida- tive hemolysis.Results: Dorzolamide/timolol (Cosopt AOA was higher than that of other fixed combinations and increased with the quantity of the drugs added to the model system: 40%, 52% and 75% in 30 μl, 60 μl and 90 μl respectively.Conclusion: these findings suggest that dorzolamide/timolol fixed combination has potential advantages over the other fixed combinations due to its high antioxidant activity and might be used as the neuroptotective agent for glaucoma treatment.

  2. Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model.

    Science.gov (United States)

    Prentice, Howard; Gharibani, Payam M; Ma, Zhiyuan; Alexandrescu, Anamaria; Genova, Rafaella; Chen, Po-Chih; Modi, Jigar; Menzie, Janet; Pan, Chunliu; Tao, Rui; Wu, Jang-Yen

    2017-01-01

    Taurine, as a free amino acid, is found at high levels in many tissues including brain, heart and skeletal muscle and is known to demonstrate neuroprotective effects in a range of disease conditions including stroke and neurodegenerative disease. Using in vitro culture systems we have demonstrated that taurine can elicit protection against endoplasmic reticulum stress (ER stress) from glutamate excitotoxicity or from excessive reactive oxygen species in PC12 cells or rat neuronal cultures. In our current investigation we hypothesized that taurine treatment after stroke in the rat middle cerebral artery occlusion (MCAO) model would render protection against ER stress processes as reflected in decreased levels of expression of ER stress pathway components. We demonstrated that taurine elicited high level protection and inhibited both ATF-6 and IRE-1 ER stress pathway components. As ischemic stroke has a complex pathology it is likely that certain combination treatment approaches targeting multiple disease mechanisms may have excellent potential for efficacy. We have previously employed the partial NMDA antagonist DETC-MeSO to render protection against in vivo ischemic stroke using a rat cerebral ischemia model. Here we tested administration of subcutaneous administration of 0.56 mg/kg DETC-MeSO or 40 mg/kg of taurine separately or as combined treatment after a 120 min cerebral ischemia in the rat MCAO model. Neither drug alone demonstrated protection at the low doses employed. Remarkably however the combination of low dose DETC-MeSO plus low dose taurine conferred a diminished infarct size and an enhanced Neuroscore (reflecting decreased neurological deficit). Analysis of ER stress markers pPERK, peIF-2-alpha and cleaved ATF-6 all showed decreased expression demonstrating that all 3 ER stress pathways were inhibited concurrent with a synergistic protective effect by the post-stroke administration of this DETC-MeSO-taurine combination treatment.

  3. Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Jiri Ruzicka

    2018-01-01

    Full Text Available Systematic inflammatory response after spinal cord injury (SCI is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB open-field locomotor test, flat beam test. Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43. Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

  4. Automatic vibration mode selection and excitation; combining modal filtering with autoresonance

    Science.gov (United States)

    Davis, Solomon; Bucher, Izhak

    2018-02-01

    Autoresonance is a well-known nonlinear feedback method used for automatically exciting a system at its natural frequency. Though highly effective in exciting single degree of freedom systems, in its simplest form it lacks a mechanism for choosing the mode of excitation when more than one is present. In this case a single mode will be automatically excited, but this mode cannot be chosen or changed. In this paper a new method for automatically exciting a general second-order system at any desired natural frequency using Autoresonance is proposed. The article begins by deriving a concise expression for the frequency of the limit cycle induced by an Autoresonance feedback loop enclosed on the system. The expression is based on modal decomposition, and provides valuable insight into the behavior of a system controlled in this way. With this expression, a method for selecting and exciting a desired mode naturally follows by combining Autoresonance with Modal Filtering. By taking various linear combinations of the sensor signals, by orthogonality one can "filter out" all the unwanted modes effectively. The desired mode's natural frequency is then automatically reflected in the limit cycle. In experiment the technique has proven extremely robust, even if the amplitude of the desired mode is significantly smaller than the others and the modal filters are greatly inaccurate.

  5. Improved medical image modality classification using a combination of visual and textual features.

    Science.gov (United States)

    Dimitrovski, Ivica; Kocev, Dragi; Kitanovski, Ivan; Loskovska, Suzana; Džeroski, Sašo

    2015-01-01

    In this paper, we present the approach that we applied to the medical modality classification tasks at the ImageCLEF evaluation forum. More specifically, we used the modality classification databases from the ImageCLEF competitions in 2011, 2012 and 2013, described by four visual and one textual types of features, and combinations thereof. We used local binary patterns, color and edge directivity descriptors, fuzzy color and texture histogram and scale-invariant feature transform (and its variant opponentSIFT) as visual features and the standard bag-of-words textual representation coupled with TF-IDF weighting. The results from the extensive experimental evaluation identify the SIFT and opponentSIFT features as the best performing features for modality classification. Next, the low-level fusion of the visual features improves the predictive performance of the classifiers. This is because the different features are able to capture different aspects of an image, their combination offering a more complete representation of the visual content in an image. Moreover, adding textual features further increases the predictive performance. Finally, the results obtained with our approach are the best results reported on these databases so far. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. [Efficacy of combined modality therapy for intractable difficult-to-treat rhinosinusitis].

    Science.gov (United States)

    Yang, Quyun; Zhao, Kan; Shen, Yi; Shen, Zhiseng; Yu, Jie

    2016-01-01

    To investigate the clinical effects of the combined modality therapy for the patients with difficult-to-treat rhinosinusitis (DTRS). The clinical data involving 42 patients with DTRS were analyzed retrospectively. All patients received revision endoscopic sinus surgery (ESS) and combined modality therapy systematically and individually. The clinical effects of all patients were observed 6- and 12-month following revision ESS. Forty-two patients were followed up for 6 months, whereas 35 patients were followed for 12 months post operation. VAS scores of the patients significantly improved (P 0.05) between 6- and 12-month post operation. Moreover, Lund-Kennedy scores by endoscopy significantly improved (P 0.05) between 6- and 12-month postoperatively. Additionally, within 6 months follow-up, 16 of 42 patients (38.1%) were cured, 19 of 42 patients (45.2%) were improved, and 7 of 42 patients (16.7%) were ineffective. The total effective rate in all patients was 83.3% 6 months postoperatively. While within 12 months follow-up, 11 of 35 patients (31.4%) were cured, 15 of 35 patients (42.9%) were improved, and 9 of 35 patients (25.7%) were ineffective. Hence, the total effective rate in 35 patients was 74.3% after 12-month follow-up. There was no statistic difference (χ² = 1.019, P > 0.05) between 6- and 12-month postoperatively. Appropriate revision ESS plus the combined modality therapy has been proven to be an effective method for the treatment of DTRS. The clinical effects in this study are significant and stable, and thus it is worthy of further clinical applications.

  7. Combining Acceleration and Displacement Dependent Modal Frequency Responses Using an MSC/NASTRAN DMAP Alter

    Science.gov (United States)

    Barnett, Alan R.; Widrick, Timothy W.; Ludwiczak, Damian R.

    1996-01-01

    Solving for dynamic responses of free-free launch vehicle/spacecraft systems acted upon by buffeting winds is commonly performed throughout the aerospace industry. Due to the unpredictable nature of this wind loading event, these problems are typically solved using frequency response random analysis techniques. To generate dynamic responses for spacecraft with statically-indeterminate interfaces, spacecraft contractors prefer to develop models which have response transformation matrices developed for mode acceleration data recovery. This method transforms spacecraft boundary accelerations and displacements into internal responses. Unfortunately, standard MSC/NASTRAN modal frequency response solution sequences cannot be used to combine acceleration- and displacement-dependent responses required for spacecraft mode acceleration data recovery. External user-written computer codes can be used with MSC/NASTRAN output to perform such combinations, but these methods can be labor and computer resource intensive. Taking advantage of the analytical and computer resource efficiencies inherent within MS C/NASTRAN, a DMAP Alter has been developed to combine acceleration- and displacement-dependent modal frequency responses for performing spacecraft mode acceleration data recovery. The Alter has been used successfully to efficiently solve a common aerospace buffeting wind analysis.

  8. Retrospective evaluation of combined modality treatment and prognostic factors in patients with esophageal cancer

    International Nuclear Information System (INIS)

    Neuhof, Dirk; Neumayer, Florian; Debus, Juergen; Einbeck, Wolfgang; Haschemian, Kai; Mai, Sabine K.; Wenz, Frederik; Hochhaus, Andreas; Willeke, Frank; Rudi, Jochen

    2005-01-01

    The influence of prognostic factors and combined modality treatment on survival was evaluated retrospectively for 156 patients with esophageal cancer receiving radiotherapy in different modalities between 1991 and 2001 at the Univ. of Heidelberg and the Universitaetsklinikum Mannheim. Forty-six patients (29.5%) were treated with radiotherapy alone, 74 patients (47.4%) had combined radiochemotherapy and 36 patients (23.1%) were operated on after receiving neoadjuvant radiochemotherapy. The median follow-up time was 10 months. Female patients showed a significantly better overall survival compared with male patients (p=0.031), younger patients (age 60 years) (p=0.02). Patients with hemoglobin concentration>13.4 g/dl before therapy (median hemoglobin concentration) had a significantly better overall survival than patients with lower hemoglobin concentration (p=0.044). Patients who received combined radiochemotherapy (with or without operation) had a survival advantage compared with radiotherapy alone. Overall survival after neoadjuvant treatment followed by operation was significantly better than in the two other groups, median survival times were 20 vs. 9 (RCHT) vs. 8 months (RT) (p=0.003). The data presented show for the first time that hemoglobin concentration in addition to gender and age was a prognostic factor for patients with esophageal cancer. A low hemoglobin value was a negative predictor

  9. Survival and Failure Outcomes in Primary Thyroid Lymphomas: A Single Centre Experience of Combined Modality Approach

    OpenAIRE

    Kumar, Ritesh; Khosla, Divya; Kumar, Narendra; Ghoshal, Sushmita; Bera, Anjan; Das, Ashim; Sharma, Suresh Chander

    2013-01-01

    Primary thyroid lymphoma (PTL) is a rare malignancy and represents 2%–5% of all thyroid malignancies and 1%–2.5% of all malignant lymphomas. We present our institute’s experience in combined modality management of 16 successive patients of PTL treated from 2005 to 2010. The median age of the patients was 56.0 years. Five patients were males, and 11 patients were females. An enlarging thyroid mass was the most common presenting symptom. 14 patients had diffuse large B-cell lymphoma, and 2 pati...

  10. [Combined-modality therapy for 150 cases of early-stage Hodgkin's lymphoma].

    Science.gov (United States)

    Niu, Yi; Shi, Yuan-kai; He, Xiao-hui; Feng, Feng-yi; Zhou, Li-qiang; Gu, Da-zhong

    2008-08-01

    To compare the efficacy of chemotherapy alone, radiotherapy alone and combined-modality therapy in the treatment for early-stage Hodgkin's lymphoma (HL). From 1999 to 2002, totally 150 patients with stage I or II HL were treated in our hospital. They were stratified into several groups based on initial treatment strategy: chemotherapy alone (CT group, n = 22), radiotherapy alone (RT group, n = 18), combined-modality therapy (CMT group, n = 109) and surgical resection (SR group, n = 1). Chemotherapy regimens were mainly ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) and MOPP (mechlorethamine, vincristine, procarbazine and prednisone). Radiotherapy modes included involved field radiotherapy (IFRT), extended field radiotherapy (EFRT) and sub-total nodal irradiation (STNI). The pathological types included nodular sclerosis (NS, n = 84), mixed-cellularity (MC, n = 39), lymphocyte-predominant (LP, n = 23), lymphocyte-depleted (LD, n = 3) and nodular lymphocyte predominant Hodgkin's disease (NLPHD, n = 1). Of those, 72 were evaluble in terms of prognostic factors. No poor prognostic factor was found in 36.1% or 29.2% of the patients according to EORTC or GHSG criteria, respectively. There were 33 patients with complete response (CR), 109 with partial response (PR), 5 with stable disease (SD) and 3 with progressive disease (PD) after initial therapy. The median follow-up period was 71.5 months. The overall 7-yr survival rate was 89.3%, and treatment failure rate at 6 years was 18.8%. The response rate of CMT group was superior to that of CT group, and the patients with nodular sclerosis or mixed-cellularity type had significantly lower risk of treatment failure (P = 0.009 and 0.019, respectively). The multivariate analysis revealed that the treatment strategies affected the prognosis significantly. The risk of failure of chemotherapy alone was 2.52 times higher than that of combined-modality therapy (P = 0.004). No predictive factor affecting OS was identified

  11. Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older.

    Science.gov (United States)

    Margalit, Danielle N; Mamon, Harvey J; Ancukiewicz, Marek; Kobayashi, Wendy; Ryan, David P; Blaszkowsky, Lawrence S; Clark, Jeffrey; Willett, Christopher G; Hong, Theodore S

    2011-12-01

    To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham & Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed≥4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p=0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p=1.0). The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of combined modality therapy for rectal cancer should be performed

  12. Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer.

    Science.gov (United States)

    Shaikh, Talha; Meyer, Joshua E; Horwitz, Eric M

    2017-07-01

    Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

    2010-01-01

    Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication...

  14. Nonoperative approach to locally advanced rectal cancer after neoadjuvant combined modality therapy: challenges and opportunities from a surgical perspective.

    Science.gov (United States)

    Fischkoff, Katherine N; Ruby, Jeannine A; Guillem, José G

    2011-12-01

    This review contains a surgical perspective on the evolution of the nonoperative approach to patients with locally advanced rectal cancer who have a clinical complete response after neoadjuvant combined modality therapy, including accuracy of pathologic complete response identification, the timing between neoadjuvant combined modality therapy and assessment of response, the extent of long-term follow-up, and the likelihood of surgical salvage after an initial nonoperative approach. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy

    OpenAIRE

    Sultana, A; Tudur Smith, C; Cunningham, D; Starling, N; Tait, D; Neoptolemos, J P; Ghaneh, P

    2007-01-01

    There is no consensus on the management of locally advanced pancreatic cancer, with either chemotherapy or combined modality approaches being employed (Maheshwari and Moser, 2005). No published meta-analysis (Fung et al, 2003; Banu et al, 2005; Liang, 2005; Bria et al, 2006; Milella et al, 2006) has included randomised controlled trials employing radiation therapy. The aim of this systematic review was to compare the following: (i) chemoradiation followed by chemotherapy (combined modality th...

  16. Survival and Failure Outcomes in Primary Thyroid Lymphomas: A Single Centre Experience of Combined Modality Approach

    Directory of Open Access Journals (Sweden)

    Ritesh Kumar

    2013-01-01

    Full Text Available Primary thyroid lymphoma (PTL is a rare malignancy and represents 2%–5% of all thyroid malignancies and 1%–2.5% of all malignant lymphomas. We present our institute’s experience in combined modality management of 16 successive patients of PTL treated from 2005 to 2010. The median age of the patients was 56.0 years. Five patients were males, and 11 patients were females. An enlarging thyroid mass was the most common presenting symptom. 14 patients had diffuse large B-cell lymphoma, and 2 patients had follicular lymphoma. The most common stage of presentation was stage II comprising 6 (37.5% patients. All patients received CCT, and only 12 patients received involved field RT with a median dose of 36.0 Gy. 10 patients (62.5% had CR, and 6 patients (27.5% had PR. Eight patients had disease progression in subsequent followup and this included the initial 6 patients with PR. The 5-year DFS was 40.0%, and median DFS was 47 months. The 5-year OS was 41.0%, and median OS was 51 months. Most common presentation in our series was locally advanced tumors. Most of these patients require combined modality management. Risk-adapted and multimodality approach is the need of the hour to achieve good control rates while minimizing treatment related toxicity.

  17. [Prognostic evaluations of recurrent gliomas and preliminary efficacies of combined modality therapy].

    Science.gov (United States)

    Zhang, Xin; Yao, Yu; Qin, Zhi-yong; Wang, Yang; Wu, Jin-song; Mao, Ying; Zhou, Liang-fu

    2013-01-01

    To evaluate the prognosis and efficacies of comprehensive treatment for recurrent gliomas. A total of 62 patients diagnosed as recurrent gliomas at our hospital between May 2007 and January 2012 were reviewed and analyzed. The investigators compared the prognosis of different grades of gliomas and evaluated the efficacies of combined modality therapy of surgery, radiotherapy, chemotherapy and immunotherapy. Their median periods of time-to-progression (TTP) and overall survival (OS) were 6.0 and 13.0 months respectively. The median TTP of WHO grade II (n = 21), III (n = 13) and IV (n = 28) recurrent gliomas were 9.0, 9.0 and 5.0 months respectively. And the average OS of WHO grade II, III and IV recurrent gliomas were 26.6, 21.4 and 13.8 months respectively. The efficacious rate of chemotherapy was 26.7%. Combined modality therapy based on chemotherapy may moderately improve the prognosis of recurrent gliomas. And the pathological grades of primary tumors are correlated with the prognosis of recurrent gliomas.

  18. Neuroprotection in glaucoma

    Science.gov (United States)

    Vasudevan, Sushil K; Gupta, Viney; Crowston, Jonathan G

    2011-01-01

    Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications. PMID:21150020

  19. [Long-term survival following postoperative combined modality therapy for pancreatic cancer].

    Science.gov (United States)

    Miyazawa, Kotaro; Yoshioka, Shigeru; Shiobara, Masayuki; Wakatsuki, Kazuo; Kataoka, Masaaki; Arai, Syuka; Yamazaki, Kazuhito

    2014-11-01

    A 69-year-old woman with back pain underwent distal pancreatectomy with left adrenectomy for advanced pancreatic cancer pathologically diagnosed as poorly differentiated invasive ductal carcinoma with retroperitoneal and perineural invasion, pT3N0M0, Stage III. The patient received adjuvant chemotherapy with S-1 for 6 months. However, 3 years after surgery, computed tomography (CT) revealed para-aorticlymph node (LN) recurrence. Treatment with gemcitabine (GEM) was begun and continued for 3 years. Following progression of the LN recurrence 5 and half years after surgery, administration of radiotherapy reduced diarrhea and back pain. Supportive care combined with radio-frequency ablation(RFA)was provided for multiple liver metastasis 5 years 7 months after surgery. The patient died due to gastrointestinal hemorrhage 6 years after surgery. We report long-term postoperative survival of a patient with recurrent pancreatic cancer following combined modality therapy.

  20. Integrated treatment modality of cathodal-transcranial direct current stimulation with peripheral sensory stimulation affords neuroprotection in a rat stroke model.

    Science.gov (United States)

    Liu, Yu-Hang; Chan, Su Jing; Pan, Han-Chi; Bandla, Aishwarya; King, Nicolas K K; Wong, Peter Tsun Hon; Chen, You-Yin; Ng, Wai Hoe; Thakor, Nitish V; Liao, Lun-De

    2017-10-01

    Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation ([Formula: see text]) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the [Formula: see text] ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.

  1. Indications for and results of combined modality treatment of colorectal cancer

    International Nuclear Information System (INIS)

    Gunderson, L.L.

    1999-01-01

    Combined modality chemoirradiation is commonly used as a component of treatment in combination with maximum resection for both high-risk resectable and locally advanced primary or recurrent rectal cancers. With surgically resected but high-risk rectal cancers, postoperative chemoirradiation has been shown to improve both disease control (local and distant) and survival (disease-free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health (NIH) Consensus Conference on Adjuvant treatment for patients with rectal and colon cancers. Subsequent intergroup trials are being conducted to help define optimal combinations of postoperative chemoirradiation for resected high-risk rectal cancers and to test sequencing issues of preoperative versus postoperative chemoirradiation. With locally unresectable primary or recurrent colorectal cancers, standard therapy with surgery, external beam irradiation (EBRT) and chemotherapy is often unsuccessful. When intraoperative electron irradiation (IOERT) is combined with standard treatment, local control and survival appear to be improved in separate analyses from the Mayo Clinic and the Massachusetts General Hospital (MGH). However, routine use of systemic therapy is also needed as a component of treatment, in view of high rates of systemic failure. (orig.)

  2. Indications for and results of combined modality treatment of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gunderson, L.L. [Mayo Medical School and Mayo Clinic, Rochester, MN (United States)

    1999-05-01

    Combined modality chemoirradiation is commonly used as a component of treatment in combination with maximum resection for both high-risk resectable and locally advanced primary or recurrent rectal cancers. With surgically resected but high-risk rectal cancers, postoperative chemoirradiation has been shown to improve both disease control (local and distant) and survival (disease-free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health (NIH) Consensus Conference on Adjuvant treatment for patients with rectal and colon cancers. Subsequent intergroup trials are being conducted to help define optimal combinations of postoperative chemoirradiation for resected high-risk rectal cancers and to test sequencing issues of preoperative versus postoperative chemoirradiation. With locally unresectable primary or recurrent colorectal cancers, standard therapy with surgery, external beam irradiation (EBRT) and chemotherapy is often unsuccessful. When intraoperative electron irradiation (IOERT) is combined with standard treatment, local control and survival appear to be improved in separate analyses from the Mayo Clinic and the Massachusetts General Hospital (MGH). However, routine use of systemic therapy is also needed as a component of treatment, in view of high rates of systemic failure. (orig.)

  3. Posterior Reversible Encephalopathy Syndrome During Combined Modality Therapy for Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Wakasaki, Takahiro; Gotoh, Seiji; Tomonobe, Eri; Mihara, Takenao; Fukushima, Junichi

    2016-10-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare and acute disease with central nervous system symptoms. Without appropriate therapy, patients may exhibit a poor prognosis. PRES should be recognized as a possible problem during therapy for head and neck squamous cell carcinoma (HNSCC). A 56-year-old female developed PRES during combined modality therapy for HNSCC. On the fourth day after surgery and following chemoradiotherapy, PRES developed with a sudden visual disorder, followed by headache located at the back of the head and convulsions accompanied by impaired consciousness. We diagnosed PRES based on the clinical manifestations and magnetic resonance imaging data. The patient recovered from PRES by appropriate treatment. This is the first case report of PRES developed during treatment for HNSCC. Masked by other cerebrovascular disorders, more cases of PRES could exist than usually expected; therefore, we should consider PRES as a differential diagnosis for central nervous system disorders developing during high-intensity therapy. © The Author(s) 2016.

  4. Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC.

    Science.gov (United States)

    Mak, Raymond H; Doran, Elizabeth; Muzikansky, Alona; Kang, Josephine; Neal, Joel W; Baldini, Elizabeth H; Choi, Noah C; Willers, Henning; Jackman, David M; Sequist, Lecia V

    2011-01-01

    Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described. We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan-Meier analysis, the log-rank test, and multivariate Cox regression models. All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders. We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.

  5. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy.

    Science.gov (United States)

    Sultana, A; Tudur Smith, C; Cunningham, D; Starling, N; Tait, D; Neoptolemos, J P; Ghaneh, P

    2007-04-23

    There is no consensus on the management of locally advanced pancreatic cancer, with either chemotherapy or combined modality approaches being employed (Maheshwari and Moser, 2005). No published meta-analysis (Fung et al, 2003; Banu et al, 2005; Liang, 2005; Bria et al, 2006; Milella et al, 2006) has included randomised controlled trials employing radiation therapy. The aim of this systematic review was to compare the following: (i) chemoradiation followed by chemotherapy (combined modality therapy) vs best supportive care (ii) radiotherapy vs chemoradiation (iii) radiotherapy vs combined modality therapy (iv) chemotherapy vs combined modality therapy (v) 5FU-based combined modality treatment vs another-agent-based combined modality therapy. Relevant randomised controlled trials were identified by searching databases, trial registers and conference proceedings. The primary end point was overall survival and secondary end points were progression-free survival/time-to-progression, response rate and adverse events. Survival data were summarised using hazard ratio (HR) and response-rate/adverse-event data with relative risk. Eleven trials involving 794 patients met the inclusion criteria. Length of survival with chemoradiation was increased compared with radiotherapy alone (two trials, 168 patients, HR 0.69; 95% confidence interval (CI) 0.51-0.94), but chemoradiation followed by chemotherapy did not lead to a survival advantage over chemotherapy alone (two trials, 134 patients, HR 0.79; CI 0.32-1.95). Meta-analyses could not be performed for the other comparisons. A survival benefit was demonstrated for chemoradiation over radiotherapy alone. Chemoradiation followed by chemotherapy did not demonstrate any survival advantage over chemotherapy alone, but important clinical differences cannot be ruled out due to the wide CI.

  6. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model

    Directory of Open Access Journals (Sweden)

    Yisong Qian

    2016-08-01

    Full Text Available Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC staining, neuronal damage was assessed by Haematoxylin Eosin (H&E staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  7. When Negation and Epistemic Modality Combine: The Role of Information Strength in Child Language

    Science.gov (United States)

    Moscati, Vincenzo; Crain, Stephen

    2014-01-01

    Negative sentences with epistemic modals (e.g., John "might" not come/John "can" not come) contain two logical operators, negation and the modal, which yields a potential semantic ambiguity depending on scope assignment. The two possible readings are in a subset/superset relation, such that the strong reading ("can…

  8. Organ preservation in invasive bladder cancer: Brachytherapy, an alternative to cystectomy and combined modality treatment?

    International Nuclear Information System (INIS)

    Pos, Floris; Horenblas, Simon; Dom, Paul; Moonen, Luc; Bartelink, Harry

    2005-01-01

    Purpose: To evaluate our long-term results of bladder preservation with brachytherapy in the treatment of bladder cancer. Methods and materials: Between 1987 and 2000, 108 patients with T1-G3 and T2-T3a stages of bladder cancer were treated with a transurethral resection (TUR) and a course of external beam radiotherapy (30 Gy in 15 fractions) followed by brachytherapy (40 Gy). All tumors were solitary lesions with a diameter ≤5 cm. Median follow-up was 54 months (range, 1-178 months). Results: The 5-year and 10-year overall survival rates were 62% and 50%, respectively. The 5-year and 10-year disease-specific survival rates were 73% and 67%, respectively. The actuarial local control rate was 73% at 5 and 73% at 10 years, respectively. The 5-year and 10-year disease-specific survival rates for patients with a preserved bladder were 68% and 59%, respectively. Of all long-term surviving patients, 90% preserved their native bladders. The treatment was well tolerated. Acute toxicity was mild. Two patients experienced serious late toxicity: 1 patient developed a persisting vesicocutaneous fistula and the other a stricture of the urethra and ureters. Conclusion: For patients with solitary, organ confined invasive bladder cancer ≤5 cm, bladder preservation with brachytherapy is an excellent alternative to radical cystectomy and combined modality treatment

  9. The Improved Sensitivity to Crossmodal Asynchrony Caused by Voluntary Action: Comparing Combinations of Sensory Modalities

    Directory of Open Access Journals (Sweden)

    Norimichi Kitagawa

    2011-10-01

    Full Text Available The brain has to assess the fine temporal relationship between voluntary actions and their sensory effects to achieve precise spatiotemporal control of body movement. Recently we found that voluntary action improved the subsequent perceptual temporal discrimination between somatosensory and auditory events. In voluntary condition, participants actively pressed a button and a noise burst was presented at various onset asynchronies relative to the button press. The participants made either ‘sound-first’ or ‘touch-first’ responses. We found that the temporal order judgment performance in the voluntary condition (as indexed by just noticeable difference was significantly better than that when their finger was passively stimulated (passive condition. Temporal attention and comparable involuntary movement did not explain the improvement caused by the voluntary action. The results suggest that predicting sensory consequences via a ‘forward’ model enhances perceptual temporal resolution for precise control of the body. The present study examined whether this improved temporal sensitivity caused by the voluntary action is also observed for the other combinations of sensory modalities. We compared the effects of voluntary action on the temporal sensitivity between auditory-somatosensory, visual-somatosensory, and somatosensory-somatosensory stimulus pairs.

  10. [Current status and treatment results of combined modality therapy for locally recurrent rectal cancer].

    Science.gov (United States)

    Koyama, Motoi; Murata, Akihiro; Sakamoto, Yoshiyuki; Morohashi, Hajime; Akasaka, Harue; Yokoyama, Hiroshi; Hatayama, Yoshiomi; Kawaguchi, Hideo; Hakamada, Kenichi

    2012-11-01

    The aim of this study was to clarify the current status of combined modality therapy for locally recurrent rectal cancer. Between 2000 and 2011, 43 patients(26 men and 17 women; mean age, 60 years) developed local pelvic recurrence after curative surgery. The recurrence pattern was almost equally distributed as 53% (23/43) pelvic, and 47% (20/43) pelvic and metastatic disease. Regarding the form of local recurrence, localized type and lateral spread type were present in 25 and 18 patients, respectively. In all, 24 patients underwent surgical resection for recurrent disease, and 87% of these patients underwent potentially curative surgery. The 3- and 5-year overall survival rates for patients who were treated with surgical resection were 42% and 29%, respectively. These results were significantly favorable when compared to the non-surgical group of patients who were treated with chemoradiotherapy or chemotherapy. Localized type recurrence is a statistically significant prognostic factor for improved survival compared to lateral spread type recurrence. Preoperative chemoradiotherapy and surgical resection should be a standard treatment option for patients with localized type recurrence, and chemoradiotherapy is better indicated for patients with lateral spread type recurrence.

  11. Thermoradiation therapy in combined modality treatment for locally advanced laryngeal and hypopharyngeal cancer

    Science.gov (United States)

    Choynzonov, E. L.; Startseva, Zh. A.; Gribova, O. V.; Mukhamedov, M. R.; Spivakova, I. O.

    2017-09-01

    The article presents the results of combined modality treatment for stage III-IV (T3N0-2M0) laryngeal and hypopharyngeal cancers. All patients (55) were divided into 2 groups. Group I patients (n = 25) received pre-operative thermoradiation therapy and Group II patients (n = 30) received pre-operative radiation therapy alone. The follow-up period was 6-24 months. In Group I patients, partial tumor regression was achieved in 21 (84%) patients and stable disease was observed in 4 (16%) patients. In group II patients, partial tumor regression and stable disease were diagnosed in 18 (60%) and 12 (49%) patients, respectively. Local and regional recurrences occurred in 1 patient (4%) of Group I within the first year of follow-up and in 11 patients of Group II (7 within the first year and 4 within two years of follow-up). The 2-year overall survival rate was 100% in Group I patients and 76.7% ± 10.1% in Group II patients. Disease-free survival rates were 96.6 ± 3.5% and 63.3 ± 13.9%, respectively.

  12. Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients.

    Science.gov (United States)

    Bishop, Andrew J; Zagars, Gunar K; Torres, Keila E; Hunt, Kelly K; Cormier, Janice N; Feig, Barry W; Guadagnolo, B Ashleigh

    2015-09-01

    The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n = 42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy). Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population.

    Science.gov (United States)

    Apland, James P; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Pidoplichko, Volodymyr I; Rossetti, Katia; Braga, Maria F M

    2018-05-01

    The currently Food and Drug Administration-approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABA A receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD 50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe-depending on the region-in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. U.S. Government work not protected by U.S. copyright.

  14. The burden of overtreatment: comparison of toxicity between single and combined modality radiation therapy among low risk prostate cancer patients.

    Science.gov (United States)

    Jiang, Renjian; Tomaszewski, Jeffrey J; Ward, Kevin C; Uzzo, Robert G; Canter, Daniel J

    2015-02-01

    To compare radiation related toxicities among men with low risk prostate cancer treated with single or multimodal radiation therapy. The SEER-Medicare linked database was used to assess the relationship between treatment type and toxicity among men with low risk prostate cancer treated with brachytherapy (BT), external beam radiation therapy (EBRT), or combined therapy between 2004 and 2007. Inverse probability of treatment weighting was utilized to minimize selection bias and control for confounding. Multivariate logistic regression models were used to explore the relationship between treatment and outcomes. Overall 1915 (43.9%), 1893 (43.4%), and 555 (12.7%) patients were treated with EBRT, BT, and combined therapy, respectively. In univariate analyses, combined modality radiation was more toxic than BT alone for GU incontinence (56.76% versus 49.08%), GU obstruction (21.26% versus 19.70%), and erectile dysfunction (22.52% versus 22.24%) (p combined modality radiation was more toxic for GI bleeding (7.21% versus 6.21%), GU incontinence (56.76% versus 29.24%), GU obstruction (21.26% versus 14.15%), and erectile dysfunction (22.52% versus 15.35%) (p combined modality treatment and lowest for the group treated with EBRT. After multivariate adjustment, EBRT alone demonstrated protective effects against GU obstruction (OR 0.56 [CI 0.50-0.63]), GI bleeding (OR 0.57 [CI 0.48-0.67]), GU incontinence (OR 0.39 [CI 0.36-0.43]), and erectile dysfunction (OR 0.68 [CI 0.61-0.76]) when compared to combined therapy. The use of combined modality radiation therapy in low risk prostate cancer patients is discordant with clinical guidelines and associated with a significantly increased burden of associated toxicity when compared to EBRT monotherapy. Prudent patient selection and judicious use of combined therapy among men with low risk prostate cancer represents a targetable area to reduce the burden of overtreatment.

  15. Long term observations in combined modality therapy for limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    Colletier, Philip J.; Komaki, Ritsuko; Schea, Randi A.; Allen, Pamela; Cox, James D.

    1997-01-01

    Purpose/Objective: With the discovery that patients with small cell lung cancer (SCLC) exhibit a high level of sensitivity to both chemotherapy and radiotherapy, the treatment of SCLC became a model for the success of combined modality treatment. In this retrospective review, we analyze the outcomes and patterns of failure when patients are treated with chemotherapy and thoracic irradiation. The relative values of sequential and concurrent chemotherapy, in conjunction with chest irradiation, are assessed. The potential benefit of prophylactic cranial irradiation is explored. The impact of prognostic factors for long term survival of SCLC patients are examined to identify pretreatment patient characteristics and treatment parameters which might predict for a favorable outcome. Materials and Methods: We identified 190 patients treated at M.D. Anderson Cancer Center from January 1985 to December 1992 with curative intent for limited stage SCLC. Prognostic factors were determined using univariate and multivariate analysis. The significant covariates for each outcome endpoint were evaluated. Probabilities of local failure, overall survival, relapse-free survival, and distant metastasis-free survival were calculated from the time of treatment using actuarial life table analysis. Results: The median age was 61, with 51% males. There were 119 patients treated sequentially, and 71 concurrently. The Karnofsky Performance Status was >= 90 in 48% of patients in the concurrent cohort, vs. 35% of the sequential group. Prophylactic cranial irradiation (PCI) was delivered in 117 cases (62%). There were 51 long term survivors, defined as survival >=36 months. The median follow-up in surviving patients was 75 months. At the time of the analysis, 166 patients (87%) had expired. The crude 2 and 3 year survival rate for the entire group was 38.4% and 26.8%, respectively. The actuarial 2-year survival was 39.9%, and at 3 years the actuarial survival was 27.8%. The median actuarial

  16. Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients

    International Nuclear Information System (INIS)

    Bishop, Andrew J.; Zagars, Gunar K.; Torres, Keila E.; Hunt, Kelly K.; Cormier, Janice N.; Feig, Barry W.; Guadagnolo, B. Ashleigh

    2015-01-01

    Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n=42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy). Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P<.001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P<.001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P<.001) and RT dose of ≥60 Gy (P<.001). Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended

  17. Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, Andrew J.; Zagars, Gunar K. [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Torres, Keila E.; Hunt, Kelly K.; Cormier, Janice N.; Feig, Barry W. [Department of Surgical Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Guadagnolo, B. Ashleigh, E-mail: aguadagn@mdanderson.org [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Department of Health Services Research, MD Anderson Cancer Center, Houston, Texas (United States)

    2015-09-01

    Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n=42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy). Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P<.001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P<.001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P<.001) and RT dose of ≥60 Gy (P<.001). Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended.

  18. Pulmonary recurrence predominates after combined modality therapy for rectal cancer: an original retrospective study.

    Science.gov (United States)

    Ding, Peirong; Liska, David; Tang, Peter; Shia, Jinru; Saltz, Leonard; Goodman, Karyn; Downey, Robert J; Nash, Garrett M; Temple, Larissa K; Paty, Philip B; Guillem, José G; Wong, W Douglas; Weiser, Martin R

    2012-07-01

    To characterize patterns of recurrence in locally advanced rectal cancer treated with combined modality therapy (CMT): neoadjuvant chemoradiation + total mesorectal excision + adjuvant chemotherapy. A total of 593 consecutive rectal cancer patients (1998 to 2007) with locally advanced (stage II/III) disease (noted on endorectal ultrasound or magnetic resonance imaging) who received CMT were analyzed for patterns of recurrence. After median 44-month follow-up (interquartile range, 25 to 64 months), 119 patients (20%) recurred: 105 distant, 7 local, 7 local and distant, and 112 distant-only recurrence. Ninety-three (78%) had single-organ recurrence, and 26 (22%) had multiple-organ recurrence. The most common site of distant recurrence was lung (69% of all patients with distant relapse); 20% had liver recurrence. Fourteen patients (2.4%) recurred locally. Pulmonary metastases were most commonly identified by computed tomographic scan versus abnormal positron emission tomographic (PET) scan or carcinoembryonic antigen (CEA). Risk factors associated with pulmonary recurrence were the following: pathologic stage, tumor distance from anal verge, lymphovascular or perineural invasion. Five-year freedom from pulmonary recurrence for patients with 0, 1, 2, or 3 risk factors was 99%, 90%, 61%, and 42%, respectively. Thirty of 59 patents with pulmonary recurrence underwent lung metastasectomy; 3-year freedom from recurrence was 37%. Unlike colon cancer, which most frequently recurs in the liver, locally advanced rectal cancer treated with CMT relapses most frequently in the lung. Pulmonary metastasis was associated with advanced pathologic stage, low-lying tumor, lymphovascular invasion, or perineural invasion. Confirmation of pulmonary metastasis usually requires serial imaging because metastases are often small when initially detected, well below the resolution of PET, and not necessarily associated with elevated CEA. Individualized risk-based surveillance strategies are

  19. Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer.

    Science.gov (United States)

    Haddock, Michael G; Miller, Robert C; Nelson, Heidi; Pemberton, John H; Dozois, Eric J; Alberts, Steven R; Gunderson, Leonard L

    2011-01-01

    To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Volumetric modulated arc therapy (VMAT) in the combined modality treatment of anal cancer patients.

    Science.gov (United States)

    Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Munoz, Fernando; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

    2016-01-01

    To report clinical and dosimetric outcomes of a consecutive series of patients with anal cancer treated with volumetric-modulated arc therapy (VMAT) concomitant to chemotherapy (CT). A cohort of 39 patients underwent VMAT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumour volume (GTV) and 42 Gy/28 fractions to the elective nodal volumes for patients with cT2N0 disease. Patients with cT3-T4/N0-N3 tumours were prescribed 54 Gy/30 fractions to the GTV and 50.4 Gy/30 fractions to the gross nodal volumes if sized ≤3 cm or 54 Gy/30 fractions if > 3 cm. Elective nodal regions were given 45 Gy/30 fractions. CT was administered concurrently following Nigro's regimen. The primary end point was acute toxicity. Secondary end points were colostomy-free survival (CFS), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Dosimetric data are also provided. Median follow-up was 21 months. Maximum acute toxicities were: dermatologic-G3: 18%; gastrointestinal-G3: 5%; genitourinary-G3: 2%; anaemia-G2: 7%; leukopenia-G3: 28%; G4: 8%; neutropenia-G3: 13%; G4: 18%; thrombocytopenia-G3: 11%; and G4: 2%. The actuarial 2-year CFS was 77.9% [95% confidence interval (CI): 54-90.4%]. Actuarial 2-year OS and CSS were 85.2% (95% CI: 60.1-95.1%), while DFS was 75.1% (95% CI: 52.4.7-88.1%). Our clinical results support the use of VMAT as a safe and effective intensity-modulated radiotherapy (IMRT) option in the combined modality treatment of anal cancer, with consistent dosimetry, mild toxicity and promising sphincter preservation and survival rates. IMRT is a standard of care for patients with anal cancer, and VMAT is a robust technical solution in this setting.

  1. Barriers to Combined-Modality Therapy for Limited-Stage Small-Cell Lung Cancer.

    Science.gov (United States)

    Pezzi, Todd A; Schwartz, David L; Mohamed, Abdallah S R; Welsh, James W; Komaki, Ritsuko U; Hahn, Stephen M; Sepesi, Boris; Pezzi, Christopher M; Fuller, Clifton D; Chun, Stephen G

    2018-01-04

    Combined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small-cell lung cancer (SCLC), but there may be barriers to utilization in the United States. To estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database. Analysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database. Utilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival. A total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P therapy (OR, 0.75; 95% CI, 0.67-0.85; P therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P therapy (HR, 0.62; 95% CI, 0.60-0.63; P therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.

  2. Pathways to improving combined modality therapy for stage III nonsmall-cell lung cancer.

    Science.gov (United States)

    Schild, S E; Vokes, E E

    2016-04-01

    Lung cancer is the leading cause of cancer deaths, having caused an estimated 1.6 million deaths worldwide in 2012 [Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-E386]. Although the majority of patients are not cured with currently available therapies, there have been significant improvements in stage-specific outcomes over time [Videtic G, Vokes E, Turrisi A et al. The survival of patients treated for stage III non-small cell lung cancer in North America has increased during the past 25 years. In The 39th Annual Meeting of the American Society of Clinical Oncology, ASCO 2003, Chicago, IL. Abstract 2557. p. 291]. This review focuses on past progress and ongoing research in the treatment of locally advanced, inoperable nonsmall-cell lung cancer (NSCLC). In the past, randomized trials revealed advantages to the use of thoracic radiotherapy (TRT) and then, the addition of induction chemotherapy. This was followed by studies that determined concurrent chemoradiotherapy to be superior to sequential therapy. A recent large phase III trial found that the administration of 74 Gy of conventionally fractionated photon-based TRT provided poorer survival than did the standard 60 Gy. However, further research on other methods of applying radiotherapy (hypofractionation, adaptive TRT, proton therapy, and stereotactic TRT boosting) is proceeding and may improve outcomes. The molecular characterization of tumors has provided more effective and less toxic targeted treatments in the stage IV setting and these agents are currently under investigation for earlier stage disease. Similarly, immune-enhancing therapies have shown promise in stage IV disease and are also being tested in the locally advanced setting. For locally advanced, inoperable NSCLC, standard therapy has evolved from TRT alone to combined modality therapy. We summarize the recent clinical trial

  3. An improved EMD method for modal identification and a combined static-dynamic method for damage detection

    Science.gov (United States)

    Yang, Jinping; Li, Peizhen; Yang, Youfa; Xu, Dian

    2018-04-01

    Empirical mode decomposition (EMD) is a highly adaptable signal processing method. However, the EMD approach has certain drawbacks, including distortions from end effects and mode mixing. In the present study, these two problems are addressed using an end extension method based on the support vector regression machine (SVRM) and a modal decomposition method based on the characteristics of the Hilbert transform. The algorithm includes two steps: using the SVRM, the time series data are extended at both endpoints to reduce the end effects, and then, a modified EMD method using the characteristics of the Hilbert transform is performed on the resulting signal to reduce mode mixing. A new combined static-dynamic method for identifying structural damage is presented. This method combines the static and dynamic information in an equilibrium equation that can be solved using the Moore-Penrose generalized matrix inverse. The combination method uses the differences in displacements of the structure with and without damage and variations in the modal force vector. Tests on a four-story, steel-frame structure were conducted to obtain static and dynamic responses of the structure. The modal parameters are identified using data from the dynamic tests and improved EMD method. The new method is shown to be more accurate and effective than the traditional EMD method. Through tests with a shear-type test frame, the higher performance of the proposed static-dynamic damage detection approach, which can detect both single and multiple damage locations and the degree of the damage, is demonstrated. For structures with multiple damage, the combined approach is more effective than either the static or dynamic method. The proposed EMD method and static-dynamic damage detection method offer improved modal identification and damage detection, respectively, in structures.

  4. Neuroprotective potential of quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Shamsher Singh

    2017-01-01

    Full Text Available 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents. Quercetin (QC is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability. Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants (e.g., Quercetin. Therefore, the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats. MPTP (100 μg/μL/rat, bilaterally was injected intranigrally on days 1, 4 and 7 using a digital stereotaxic apparatus. QC (25 and 50 mg/kg, intragastrically and QC (25 mg/kg, intragastrically in combination with piperine (2.5 mg/kg, intragastrically were administered daily for 14 days starting from day 8 after the 3rd injection of MPTP. On day 22, animals were sacrificed and the striatum was isolated for oxidative stress parameter (thiobarbituric acid reactive substances, nitrite and glutathione, neuroinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α and neurotransmitter (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid evaluations. Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance. Both QC (25 and 50 mg/kg and QC (25 mg/kg in combination with piperine (2.5 mg/kg, in particular the combination therapy, significantly improved MPTP-induced behavioral abnormalities in rats, reversed the abnormal alterations of neurotransmitters in the striatum, and alleviated

  5. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality.

    Science.gov (United States)

    Thapa, Deepak; Ahuja, Vanita

    2014-03-01

    Plantar fasciitis (PF) is the most common cause of chronic heel pain which may be bilateral in 20 to 30% of patients. It is a very painful and disabling condition which can affect the quality of life. The management includes both pharmacological and operative procedures with no single proven effective treatment modality. In the present case series, we managed three patients with PF (one with bilateral PF). Following a diagnostic medial calcaneal nerve (MCN) block at its origin, we observed reduction in verbal numerical rating scale (VNRS) in all the three patients. Two patients has relapse of PF pain which was managed with MCN block followed with pulsed radio frequency (PRF). All the patients were pain-free at the time of reporting. This case series highlights the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF.

  6. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality

    Directory of Open Access Journals (Sweden)

    Deepak Thapa

    2014-01-01

    Full Text Available Plantar fasciitis (PF is the most common cause of chronic heel pain which may be bilateral in 20 to 30% of patients. It is a very painful and disabling condition which can affect the quality of life. The management includes both pharmacological and operative procedures with no single proven effective treatment modality. In the present case series, we managed three patients with PF (one with bilateral PF. Following a diagnostic medial calcaneal nerve (MCN block at its origin, we observed reduction in verbal numerical rating scale (VNRS in all the three patients. Two patients has relapse of PF pain which was managed with MCN block followed with pulsed radio frequency (PRF. All the patients were pain-free at the time of reporting. This case series highlights the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF.

  7. Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Choy, Hak

    2004-01-01

    There has been a surge of interest in the translation of discoveries in molecular biology into clinically relevant therapies in the field of hematology/oncology. The epidermal growth factor receptor (EGFR) has been a molecular target of significant interest and investigation, and preclinical and clinical studies support a role for targeted therapy in a variety of cancers, including non-small-cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839, IMC-C225, and OSI-774 are the most clinically developed of these compounds. Interestingly, preclinical studies have demonstrated that EGFR inhibitors may have radiation-sensitizing properties, as well as increased cytotoxic activity in combination with chemotherapeutic agents, suggesting a potential role for EGFR inhibitors as an adjunct to the current combined-modality approach for therapy of Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to address the issue of determining the impact of the addition of EGFR inhibitors to the standard combined-modality regimen (chemotherapy/radiation therapy ± surgery) for Stage III NSCLC. This article reviews preclinical and clinical data supporting the role for EGFR inhibitors alone or in combination with chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide an overview of ongoing and proposed clinical studies investigating the potential role for EGFR inhibitors in Stage III NSCLC

  8. [A case of long-term survival following combined modality therapy for peritoneal disseminated recurrence of duodenal cancer].

    Science.gov (United States)

    Kabashima, Akira; Kudo, Kensuke; Nakamura, Toshihiko; Ninomiya, Mizuki; Hamatsu, Takayuki; Hasegawa, Hirofumi; Ushijima, Chie; Kitamura, Masayuki

    2012-11-01

    A 65-year-old man was diagnosed with primary duodenal cancer and he underwent pancreaticoduodenectomy in June 2006. S-1 was administered as the postoperative adjuvant chemotherapy. A peritoneal disseminated recurrence was diagnosed together with a right reniportal node and right hydronephrosis in February 2007. A ureteral stent was inserted. DOC +S-1 combination therapy was administered from March 2007. Following progression of the recurrence, CDDP+S-1 combination therapy was administered from August 2007. Temporal diminution of the recurrence was achieved with radiotherapy from May to June 2009. Following re-progression of the recurrence, biweekly CPT-11 therapy was administered from February 2010. Weekly PTX therapy was administered from January 2011. The patient died due to progression of the recurrence in June 2011, 5 years after the operation. Our patient maintained a good quality of life and achieved long-term survival by combined modality therapy for peritoneal disseminated recurrence of duodenal cancer.

  9. Combined-modality therapy for early-stage Hodgkin lymphoma: maintaining high cure rates while minimizing risks.

    Science.gov (United States)

    Kelsey, Chris R; Beaven, Anne W; Diehl, Louis F; Prosnitz, Leonard R

    2012-12-01

    Multiple randomized studies have demonstrated that chemotherapy, most commonly ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine), followed by consolidation radiation therapy is the most effective treatment program for early-stage Hodgkin lymphoma. With a combined-modality approach, the great majority of patients are cured of their disease. It is also apparent that both chemotherapy and radiation therapy can increase the risk of complications in the decades following treatment, with second cancers and cardiac disease being the most common. Most studies,evaluating such risks primarily include patients treated in decades past with what are now considered outdated approaches, including high-dose, wide-field radiation therapy. The treatment of Hodgkin lymphoma has evolved significantly, particularly in regard to radiation therapy. In combination with chemotherapy, much lower doses and smaller fields are employed, with success equivalent to that achieved using older methods. Many studies have shown a significant decline in both the rates of second cancers and the risk of cardiac disease with low-dose radiation confined to the original extent of disease. In favorable patients, as few as 2 cycles of ABVD have been shown to be effective. The current combined-modality approach seeks to maintain high cure rates but minimize risks by optimizing both chemotherapy and radiation therapy

  10. The effect of a combined modality treatment with Cisplatin and irradiation upon the survival of human melanoma cells

    International Nuclear Information System (INIS)

    Ziegler, W.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H. Muenchen, Neuherberg

    1986-01-01

    During a combined treatment of human melanoma cells with Cisplatin and irradiation under aerobic conditions, interaction between the two treatment modalities is observed. The presence of Cisplatin during irradiation leads to an increased beding, pretreatment with Cisplatin to an increased initial steepness of the survival curve irrespective of the time interval and the Cisplatin dose. Post-treatment with Cisplatin, however, does not influence the shape of the survival curve. Simultaneous treatment of human melanoma cells with Cisplatin and irradiation in hypoxia does not result in the radiosensitization seen under aerobic conditions. (orig.) [de

  11. Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk

    DEFF Research Database (Denmark)

    Franklin, J.G.; Paus, M.D.; Pluetschow, A.

    2005-01-01

    . Trialists submitted additional information concerning methods and data quality. Peto Odds Ratios (OR) with 95% confidence intervals (CI) were calculated for OS, PFS and SM-free survival. Secondary acute leukemia (AL), non-Hodgkin's lymphoma (NHL) and solid tumours (ST) were also analysed separately. MAIN......-diagnosed Hodgkin's disease are compared with respect to SM risk, overall (OS) and progression-free (PFS) survival. Further, involved-field (IF-)RT is compared to extended-field (EF-)RT. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, PubMed, EMBASE, CancerLit, LILACS, relevant conference...... proceedings, trials lists and publications. SELECTION CRITERIA: RCTs accruing 30+ patients and completing accrual before/during 2000, comparing at least two treatment modalities for newly-diagnosed HD. DATA COLLECTION AND ANALYSIS: Individual patient data were collected and assessed for data quality...

  12. Practica continua: Connecting and combining simulation modalities for integrated teaching, learning and assessment.

    Science.gov (United States)

    Ellaway, Rachel H; Kneebone, Roger; Lachapelle, Kevin; Topps, David

    2009-08-01

    Simulation modalities are generally used independently of one another, largely due to physical and operational limitations to integration. Recent developments are enabling simulators and simulation environments to progress beyond single intervention models towards integrated continua of simulation. Moving to greater integration can improve contextualisation, better management of the transition from individual simulation to clinical practice, and provide wider opportunities to synthesise skills and approaches to practice. Simulation integration may involve experiential, modelling, technical, narrative, and evaluation dimensions; it includes both direct actions and activities, and technical and systems designs. The work in developing these integration continua is ongoing and takes many forms in many places. The framework of 'practica continua' proposed in this article links theoretical approaches and practical examples of integrated uses of simulation in education.

  13. Combined EEG/MEG can outperform single modality EEG or MEG source reconstruction in presurgical epilepsy diagnosis.

    Directory of Open Access Journals (Sweden)

    Ümit Aydin

    Full Text Available We investigated two important means for improving source reconstruction in presurgical epilepsy diagnosis. The first investigation is about the optimal choice of the number of epileptic spikes in averaging to (1 sufficiently reduce the noise bias for an accurate determination of the center of gravity of the epileptic activity and (2 still get an estimation of the extent of the irritative zone. The second study focuses on the differences in single modality EEG (80-electrodes or MEG (275-gradiometers and especially on the benefits of combined EEG/MEG (EMEG source analysis. Both investigations were validated with simultaneous stereo-EEG (sEEG (167-contacts and low-density EEG (ldEEG (21-electrodes. To account for the different sensitivity profiles of EEG and MEG, we constructed a six-compartment finite element head model with anisotropic white matter conductivity, and calibrated the skull conductivity via somatosensory evoked responses. Our results show that, unlike single modality EEG or MEG, combined EMEG uses the complementary information of both modalities and thereby allows accurate source reconstructions also at early instants in time (epileptic spike onset, i.e., time points with low SNR, which are not yet subject to propagation and thus supposed to be closer to the origin of the epileptic activity. EMEG is furthermore able to reveal the propagation pathway at later time points in agreement with sEEG, while EEG or MEG alone reconstructed only parts of it. Subaveraging provides important and accurate information about both the center of gravity and the extent of the epileptogenic tissue that neither single nor grand-averaged spike localizations can supply.

  14. Combined EEG/MEG can outperform single modality EEG or MEG source reconstruction in presurgical epilepsy diagnosis.

    Science.gov (United States)

    Aydin, Ümit; Vorwerk, Johannes; Dümpelmann, Matthias; Küpper, Philipp; Kugel, Harald; Heers, Marcel; Wellmer, Jörg; Kellinghaus, Christoph; Haueisen, Jens; Rampp, Stefan; Stefan, Hermann; Wolters, Carsten H

    2015-01-01

    We investigated two important means for improving source reconstruction in presurgical epilepsy diagnosis. The first investigation is about the optimal choice of the number of epileptic spikes in averaging to (1) sufficiently reduce the noise bias for an accurate determination of the center of gravity of the epileptic activity and (2) still get an estimation of the extent of the irritative zone. The second study focuses on the differences in single modality EEG (80-electrodes) or MEG (275-gradiometers) and especially on the benefits of combined EEG/MEG (EMEG) source analysis. Both investigations were validated with simultaneous stereo-EEG (sEEG) (167-contacts) and low-density EEG (ldEEG) (21-electrodes). To account for the different sensitivity profiles of EEG and MEG, we constructed a six-compartment finite element head model with anisotropic white matter conductivity, and calibrated the skull conductivity via somatosensory evoked responses. Our results show that, unlike single modality EEG or MEG, combined EMEG uses the complementary information of both modalities and thereby allows accurate source reconstructions also at early instants in time (epileptic spike onset), i.e., time points with low SNR, which are not yet subject to propagation and thus supposed to be closer to the origin of the epileptic activity. EMEG is furthermore able to reveal the propagation pathway at later time points in agreement with sEEG, while EEG or MEG alone reconstructed only parts of it. Subaveraging provides important and accurate information about both the center of gravity and the extent of the epileptogenic tissue that neither single nor grand-averaged spike localizations can supply.

  15. Circulating proteins in response to combined-modality therapy in rectal cancer identified by antibody array screening.

    Science.gov (United States)

    Kalanxhi, Erta; Hektoen, Helga Helseth; Meltzer, Sebastian; Dueland, Svein; Flatmark, Kjersti; Ree, Anne Hansen

    2016-07-26

    The increasingly complex programs of contemporary cancer therapy emphasize the need for biological indicators of both therapeutic response and adverse effects. One example is combined-modality treatment aimed at improving long-term outcome in patients with locally advanced rectal cancer, which commonly comes at the price of extended limits of patient tolerance. In a prospective study with intensified neoadjuvant treatment of rectal cancer patients, using an antibody array, the profiling of approximately 500 proteins was performed in serial serum samples collected at different stages of the treatment course. The small number of proteins whose levels significantly changed after induction neoadjuvant chemotherapy (NACT) expanded substantially following the sequential chemoradiotherapy (CRT) and persisted four weeks later at treatment evaluation before pelvic surgery. Serum levels of proteins selected for validation of the experimental design, lipocalin-2 and matrix metalloproteinase-9, declined after NACT and gradually reverted to baseline values during the remaining neoadjuvant course. Of note, the greater the decline in post-NACT and post-CRT matrix metalloproteinase-9 levels, the more favorable progression-free survival. No correlation was found, however, with diarrhea scores, the clinical correlate of adverse therapeutic effects. Even though the findings were indicative of only tumor and not normal tissue effects, multiplex immunoassay analysis of circulating proteins in patients undergoing combined-modality therapy may in principle dissect the contribution of the individual modalities to overall systemic responses in patient outcome and tolerance. ClinicalTrials.gov NCT00278694 ; registration date: January 16, 2006, retrospective to enrollment of the first 10 patients of the current report.

  16. National patterns of care and outcomes after combined modality therapy for stage IIIA non-small-cell lung cancer.

    Science.gov (United States)

    Patel, Aalok P; Crabtree, Traves D; Bell, Jennifer M; Guthrie, Tracey J; Robinson, Clifford G; Morgensztern, Daniel; Colditz, Graham A; Kreisel, Daniel; Krupnick, A Sasha; Bradley, Jeffrey D; Patterson, G Alexander; Meyers, Bryan F; Puri, Varun

    2014-05-01

    The role of surgery in addition to chemotherapy and radiation for stage IIIA non-small-cell lung cancer (NSCLC) remains controversial. Because there are limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally and explored the outcomes with and without the addition of surgery. Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation were compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any sequence. Between 1998 and 2010, 61,339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%) received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely female patients and Caucasians, and had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months versus 15.7 months, p therapy seem to have better long-term survival.

  17. Interactive, multi-modality image registrations for combined MRI/MRSI-planned HDR prostate brachytherapy

    Directory of Open Access Journals (Sweden)

    Galen Reed

    2011-03-01

    Full Text Available Purpose: This study presents the steps and criteria involved in the series of image registrations used clinically during the planning and dose delivery of focal high dose-rate (HDR brachytherapy of the prostate. Material and methods: Three imaging modalities – Magnetic Resonance Imaging (MRI, Magnetic Resonance Spectroscopic Imaging (MRSI, and Computed Tomography (CT – were used at different steps during the process. MRSI is used for identification of dominant intraprosatic lesions (DIL. A series of rigid and nonrigid transformations were applied to the data to correct for endorectal-coil-induced deformations and for alignment with the planning CT. Mutual information was calculated as a morphing metric. An inverse planning optimization algorithm was applied to boost dose to the DIL while providing protection to the urethra, penile bulb, rectum, and bladder. Six prostate cancer patients were treated using this protocol. Results: The morphing algorithm successfully modeled the probe-induced prostatic distortion. Mutual information calculated between the morphed images and images acquired without the endorectal probe showed a significant (p = 0.0071 increase to that calculated between the unmorphed images and images acquired without the endorectal probe. Both mutual information and visual inspection serve as effective diagnostics of image morphing. The entire procedure adds less than thirty minutes to the treatment planning. Conclusion: This work demonstrates the utility of image transformations and registrations to HDR brachytherapy of prostate cancer.

  18. Combined modality therapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Recine, D.; Rowland, K.; Reddy, S.; Lee, M.S.; Bonomi, P.; Taylor, S.; Faber, L.P.; Warren, W.; Kittle, C.F.; Hendrickson, F.R.

    1990-01-01

    Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

  19. [Report of a Successful Case of Combined Modality Therapy for a Patient with Local Recurrence of Rectal Cancer].

    Science.gov (United States)

    Fukino, Nobutada; Kida, Kazutoshi; Kuboi, Youichi; Mimatsu, Kenji; Amano, Sadao

    2016-11-01

    A 67-year-old man underwent abdominoperinealresection for rectalcancer (Rb, tub2>muc, A, N1, H0, P0, M0, Cy1, Stage III a). We administered mFOLFOX6 as adjuvant chemotherapy for 6 months. Twenty-seven months after surgery, his serum tumor marker level was increased, and local recurrence in the left rear of the prostate was detected by pelvic CT. The patient selected radiation(50 Gy/25 Fr), after rejecting resection for the local recurrence. After radiation, we performed chemotherapy combined with bevacizumab. Seventeen months from the start of chemotherapy, 47 months after surgery, chemotherapy was stopped because his tumor maker levels normalized and pelvic CT revealed a partial response. At present, his progression-free survival is 7 months after completion of chemotherapy. We conclude that combined modality therapy is an option for a patient with locally recurrent rectal cancer.

  20. Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2012-08-01

    Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

  1. Combined modality treatment for PET-positive non-Hodgkin lymphoma: favorable outcomes of combined modality treatment for patients with non-Hodgkin lymphoma and positive interim or postchemotherapy FDG-PET.

    Science.gov (United States)

    Halasz, Lia M; Jacene, Heather A; Catalano, Paul J; Van den Abbeele, Annick D; Lacasce, Ann; Mauch, Peter M; Ng, Andrea K

    2012-08-01

    To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [(18)F]fluoro-2-deoxy-2-d-glucose positron emission tomography (FDG-PET) response. We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

    Directory of Open Access Journals (Sweden)

    Chao-liang Tang

    2018-01-01

    Full Text Available Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 μg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 μg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spontaneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100β and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/ (registration number: ChiCTR-IPR-16008113.

  3. Successes and Failures of Combined Modality Therapies in Head and Neck Cancer.

    Science.gov (United States)

    Bowles, Daniel W; Deutsch, Eric; Raben, David

    2016-10-01

    The paradigms for treating head and neck squamous cell carcinoma are changing as new subgroups are defined. The technical successes of improved radiation therapy are many; however, the success of novel combined therapies are few. With the emergence of human papillomavirus and the development of immunooncology agents, such as checkpoint inhibitors, are we ready to reevaluate how we use radiation and chemotherapy for locally advanced and metastatic disease-will we remain the fire or become the fire starter? Copyright © 2016. Published by Elsevier Inc.

  4. Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study

    Directory of Open Access Journals (Sweden)

    Page Stacey A

    2011-09-01

    Full Text Available Abstract Background Therapeutic massage and bodywork (TMB practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Methods Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Results Of the 5242 distributed surveys, 791 were returned (15.1%. Practitioners were predominantly female (91.7%, worked in a range of environments, primarily private (44.4% and home clinics (35.4%, and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%, with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. Conclusions The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient

  5. Treatment of Obstructive Sleep Apnea. Prospects for Personalized Combined Modality Therapy.

    Science.gov (United States)

    Deacon, Naomi L; Jen, Rachel; Li, Yanru; Malhotra, Atul

    2016-01-01

    Obstructive sleep apnea (OSA) is a common sleep disorder with serious associated morbidities. Although several treatment options are currently available, variable efficacy and adherence result in many patients either not being treated or receiving inadequate treatment long term. Personalized treatment based on relevant patient characteristics may improve adherence to treatment and long-term clinical outcomes. Four key traits of upper airway anatomy and neuromuscular control interact to varying degrees within individuals to cause OSA. These are: (1) the pharyngeal critical closing pressure, (2) the stability of ventilator chemoreflex feedback control (loop gain), (3) the negative intraesophageal pressure that triggers arousal (arousal threshold), and (4) the level of stimulus required to activated upper airway dilator muscles (upper airway recruitment threshold). Simplified diagnostic methods are being developed to assess these pathophysiological traits, potentially allowing prediction of which treatment would best suit each patient. In contrast to current practice of using various treatment modes alone, model predictions and pilot clinical trials show improved outcomes by combining several treatments targeted to each patient's pathophysiology profile. These developments could theoretically improve efficacy and adherence to treatment and in turn reduce the social and economic health burden of OSA and the associated life-threatening morbidities. This article reviews OSA pathophysiology and identifies currently available and investigational treatments that may be combined in the future to optimize therapy based on individual profiles of key patient pathophysiological traits.

  6. Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

    International Nuclear Information System (INIS)

    Matos, Tadeja; Cufer, Tanja; Cervek, Jozica; Borstnar, Simona; Kragelj, Borut; Zumer-Pregelj, Mirjana

    2000-01-01

    Purpose: The results of bladder sparing approach for the treatment of muscle-invasive bladder cancer, using a combination of transurethral resection (TUR), chemotherapy, and radiotherapy, are encouraging. The survival of patients treated by this method is similar to the survival of patients treated by radical cystectomy. The aim of our study was to find out which pretreatment characteristics influence the survival of patients treated by organ sparing approach that would enable us to identify the patients most suitable for this type of treatment. Methods and Materials: The prognostic value of different factors, such as age, gender, performance status, hemoglobin level, clinical stage, histologic grade, presence of obstructive uropathy, and completeness of TUR, has been studied in 105 patients with invasive bladder cancer, who received a bladder sparing treatment in the period from 1988 to 1995. They were treated with a combination of TUR, followed by 2-4 cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders the treatment was completed by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas nonresponders underwent cystectomy whenever feasible. Results: Our study has confirmed an independent prognostic value of performance status, histologic grade, and obstructive uropathy, for the disease-specific survival (DSS) of bladder cancer patients treated by a conservative approach. We believe that performance status best reflects the extent of disease and exerts significant influence on the extent and course of treatment, while obstructive uropathy is a good indicator of local spread of the disease, better than clinical T-stage. Our finding that histologic grade is one of the strongest prognostic factors shows that tumor biology also is a very important prognostic factor in patients treated by conservative approach. Conclusion: Patients with muscle-invasive bladder cancer who are most likely to benefit

  7. Combined modality treatment is the treatment of choice for stage I/IE intermediate and high grade non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Noordijk, E.M.; Thomas, J.; Raemaekers, J.M.M.; Meerwaldt, J.H.

    1998-01-01

    Background and purpose: In a retrospective study, the efficacy of radiotherapy alone was compared with combined modality treatment in patients with stage I/IE non-Hodgkin's lymphoma (NHL). Patients and methods: Between 1980 and 1994, 296 patients with stage I/IE non-Hodgkin's lymphoma of intermediate or high grade malignancy (according to the Working Formulation) were treated in four different institutions. All patients were included except patients that presented with NHLs localized in the central nervous system, testis or skin. Two hundred two patients were treated with radiation therapy alone and 94 patients were treated with combined modality treatment. Results: Increasing age and radiation as a single treatment (versus combined modality treatment) were highly significant adverse prognostic factors by multivariate analysis. The actuarial 10-year rates for progression-free and overall survival were 83 and 70%, respectively, for the patients treated with combined modality treatment and 47 and 43%, respectively, for the patients treated with radiation therapy alone. Conclusion: Combined modality treatment is the treatment of choice for patients with stage I/IE intermediate and high grade non-Hodgkin's lymphomas. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  8. Biomarkers of histone deacetylase inhibitor activity in a phase 1 combined-modality study with radiotherapy.

    Directory of Open Access Journals (Sweden)

    Anne Hansen Ree

    Full Text Available Following the demonstration that histone deacetylase inhibitors enhanced experimental radiation-induced clonogenic suppression, the Pelvic Radiation and Vorinostat (PRAVO phase 1 study, combining fractionated radiotherapy with daily vorinostat for pelvic carcinoma, was designed to evaluate both clinical and novel biomarker endpoints, the latter relating to pharmacodynamic indicators of vorinostat action in clinical radiotherapy.Potential biomarkers of vorinostat radiosensitizing action, not simultaneously manifesting molecular perturbations elicited by the radiation itself, were explored by gene expression array analysis of study patients' peripheral blood mononuclear cells (PBMC, sampled at baseline (T0 and on-treatment two and 24 hours (T2 and T24 after the patients had received vorinostat.This strategy revealed 1,600 array probes that were common for the comparisons T2 versus T0 and T24 versus T2 across all of the patients, and furthermore, that no significantly differential expression was observed between the T0 and T24 groups. Functional annotation analysis of the array data showed that a significant number of identified genes were implicated in gene regulation, the cell cycle, and chromatin biology. Gene expression was validated both in patients' PBMC and in vorinostat-treated human carcinoma xenograft models, and transient repression of MYC was consistently observed.Within the design of the PRAVO study, all of the identified genes showed rapid and transient induction or repression and therefore, in principle, fulfilled the requirement of being pharmacodynamic biomarkers of vorinostat action in fractionated radiotherapy, possibly underscoring the role of MYC in this therapeutic setting.

  9. LSPR and Interferometric Sensor Modalities Combined Using a Double-Clad Optical Fiber.

    Science.gov (United States)

    Muri, Harald Ian; Bano, Andon; Hjelme, Dag Roar

    2018-01-11

    We report on characterization of an optical fiber-based multi-parameter sensor concept combining localized surface plasmon resonance (LSPR) signal and interferometric sensing using a double-clad optical fiber. The sensor consists of a micro-Fabry-Perot in the form of a hemispherical stimuli-responsive hydrogel with immobilized gold nanorods on the facet of a cleaved double-clad optical fiber. The swelling degree of the hydrogel is measured interferometrically using the single-mode inner core, while the LSPR signal is measured using the multi-mode inner cladding. The quality of the interferometric signal is comparable to previous work on hydrogel micro-Fabry-Perot sensors despite having gold nanorods immobilized in the hydrogel. We characterize the effect of hydrogel swelling and variation of bulk solution refractive index on the LSPR peak wavelength. The results show that pH-induced hydrogel swelling causes only weak redshifts of the longitudinal LSPR mode, while increased bulk refractive index using glycerol and sucrose causes large blueshifts. The redshifts are likely due to reduced plasmon coupling of the side-by-side configuration as the interparticle distance increases with increasing swelling. The blueshifts with increasing bulk refractive index are likely due to alteration of the surface electronic structure of the gold nanorods donated by the anionic polymer network and glycerol or sucrose solutions. The recombination of biotin-streptavidin on gold nanorods in hydrogel showed a 7.6 nm redshift of the longitudinal LSPR. The LSPR response of biotin-streptavidin recombination is due to the change in local refractive index (RI), which is possible to discriminate from the LSPR response due to changes in bulk RI. In spite of the large LSPR shifts due to bulk refractive index, we show, using biotin-functionalized gold nanorods binding to streptavidin, that LSPR signal from gold nanorods embedded in the anionic hydrogel can be used for label-free biosensing. These

  10. Differences in Perception of Musical Stimuli among Acoustic, Electric, and Combined Modality Listeners.

    Science.gov (United States)

    Prentiss, Sandra M; Friedland, David R; Nash, John J; Runge, Christina L

    2015-05-01

    Cochlear implants have shown vast improvements in speech understanding for those with severe to profound hearing loss; however, music perception remains a challenge for electric hearing. It is unclear whether the difficulties arise from limitations of sound processing, the nature of a damaged auditory system, or a combination of both. To examine music perception performance with different acoustic and electric hearing configurations. Chord discrimination and timbre perception were tested in subjects representing four daily-use listening configurations: unilateral cochlear implant (CI), contralateral bimodal (CIHA), bilateral hearing aid (HAHA) and normal-hearing (NH) listeners. A same-different task was used for discrimination of two chords played on piano. Timbre perception was assessed using a 10-instrument forced-choice identification task. Fourteen adults were included in each group, none of whom were professional musicians. The number of correct responses was divided by the total number of presentations to calculate scores in percent correct. Data analyses were performed with Kruskal-Wallis one-way analysis of variance and linear regression. Chord discrimination showed a narrow range of performance across groups, with mean scores ranging between 72.5% (CI) and 88.9% (NH). Significant differences were seen between the NH and all hearing-impaired groups. Both the HAHA and CIHA groups performed significantly better than the CI groups, and no significant differences were observed between the HAHA and CIHA groups. Timbre perception was significantly poorer for the hearing-impaired groups (mean scores ranged from 50.3-73.9%) compared to NH (95.2%). Significantly better performance was observed in the HAHA group as compared to both groups with electric hearing (CI and CIHA). There was no significant difference in performance between the CIHA and CI groups. Timbre perception was a significantly more difficult task than chord discrimination for both the CI and CIHA

  11. LSPR and Interferometric Sensor Modalities Combined Using a Double-Clad Optical Fiber

    Directory of Open Access Journals (Sweden)

    Harald Ian Muri

    2018-01-01

    Full Text Available We report on characterization of an optical fiber-based multi-parameter sensor concept combining localized surface plasmon resonance (LSPR signal and interferometric sensing using a double-clad optical fiber. The sensor consists of a micro-Fabry-Perot in the form of a hemispherical stimuli-responsive hydrogel with immobilized gold nanorods on the facet of a cleaved double-clad optical fiber. The swelling degree of the hydrogel is measured interferometrically using the single-mode inner core, while the LSPR signal is measured using the multi-mode inner cladding. The quality of the interferometric signal is comparable to previous work on hydrogel micro-Fabry-Perot sensors despite having gold nanorods immobilized in the hydrogel. We characterize the effect of hydrogel swelling and variation of bulk solution refractive index on the LSPR peak wavelength. The results show that pH-induced hydrogel swelling causes only weak redshifts of the longitudinal LSPR mode, while increased bulk refractive index using glycerol and sucrose causes large blueshifts. The redshifts are likely due to reduced plasmon coupling of the side-by-side configuration as the interparticle distance increases with increasing swelling. The blueshifts with increasing bulk refractive index are likely due to alteration of the surface electronic structure of the gold nanorods donated by the anionic polymer network and glycerol or sucrose solutions. The recombination of biotin-streptavidin on gold nanorods in hydrogel showed a 7.6 nm redshift of the longitudinal LSPR. The LSPR response of biotin-streptavidin recombination is due to the change in local refractive index (RI, which is possible to discriminate from the LSPR response due to changes in bulk RI. In spite of the large LSPR shifts due to bulk refractive index, we show, using biotin-functionalized gold nanorods binding to streptavidin, that LSPR signal from gold nanorods embedded in the anionic hydrogel can be used for label

  12. Combined modality therapy for thoracic and head and neck cancers: a review of updated literature based on a consensus meeting.

    Science.gov (United States)

    Franco, Pierfrancesco; Fiorentino, Alba; Dionisi, Francesco; Fiore, Michele; Chiesa, Silvia; Vagge, Stefano; Cellini, Francesco; Caravatta, Luciana; Tombolini, Mario; De Rose, Fiorenza; Meattini, Icro; Mortellaro, Gianluca; Apicella, Giuseppina; Marino, Lorenza; Greto, Daniela

    2016-10-13

    Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial. The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress. The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial. Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.

  13. Carcinoma showing thymus-like element (CASTLE) of thyroid: combined modality treatment in 3 patients with locally advanced disease.

    Science.gov (United States)

    Chow, S M; Chan, J K C; Tse, L L Y; Tang, D L C; Ho, C M; Law, S C K

    2007-02-01

    To examine the value of chemotherapy, radiotherapy and surgery for treatment of locally advanced carcinoma showing thymus-like element (CASTLE) of the thyroid. Retrospective analysis of 3 Chinese patients in a tertiary referral center in Hong Kong. CASTLE is a rare thyroid malignancy with a frequency of only 0.15% (3/2033 patients) in our center. Three patients (M:F=2:1) aged 43, 49 and 62 years were studied. All 3 patients had advanced T4 disease with extensive tracheal infiltration and airway compression. None had lymph node or distant metastasis. Total thyroidectomy, combined with chemotherapy and radiotherapy, was effective in local control and symptom relief. Etoposide and carboplatin were tried in 2 patients with positive response. Neoadjuvant chemotherapy shrank the tumor rapidly and relieved symptoms of airway compression. All 3 patients had external radiotherapy resulting in good local control. In a patient with inoperable disease, chemotherapy and radiotherapy rendered the disease operable. All 3 patients were symptom-free and alive at 6, 2.5 and 1.8 years after diagnosis. CASTLE is locally infiltrative and presents at advanced T stage in this small series. Chemotherapy and radiotherapy, apart from surgery, are effective treatment modalities. In cases of inoperable disease or advanced local disease, they can be employed in combination with surgery. Organ preservation of larynx and trachea may be achieved. Chemotherapy can be very useful for rapid relief of symptoms, especially in shrinking tumor to prevent airway obstruction.

  14. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    Directory of Open Access Journals (Sweden)

    Malini Olivo

    2010-05-01

    Full Text Available Photodynamic therapy (PDT has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS, which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS, that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  15. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

    Science.gov (United States)

    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  16. Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

    International Nuclear Information System (INIS)

    Kinsella, T.J.; Loeffler, J.S.; Fraass, B.A.; Tepper, J.

    1983-01-01

    A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. Local control was achieved in nine patients (90%) with a follow-up of 30 to 119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients

  17. Combined effect of external damper and cross-tie on the modal response of hybrid two-cable networks

    Science.gov (United States)

    Ahmad, Javaid; Cheng, Shaohong; Ghrib, Faouzi

    2018-03-01

    Combining external dampers and cross-ties into a hybrid system to control bridge stay cable vibrations can address deficiencies associated with these two commonly used vibration control solutions while retaining their respective merits. Despite successful implementation of this strategy on a few cable-stayed bridges, behavior of such a structural system is still not fully understood. In the current study, an analytical model of a hybrid system consisting of two parallel taut cables interconnected by a transverse linear flexible cross-tie, with one cable also equipped with a transverse linear viscous damper close to one end support, is developed. The proposed model is validated by an experimental work in the literature and an independent numerical simulation. A parametric study is conducted to comprehend the impact of main design parameters on the performance of a hybrid system in terms of the in-plane frequency, the damping and the degree of mode localization of the system's fundamental mode. In addition, the concept of isoquant curve is applied not only to appreciate the effect of simultaneous variation in main design parameters on the modal behavior of a hybrid system, but also to identify the optimal ranges of these parameters to achieve the required cable vibration control effect.

  18. Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Solanki AA

    2013-08-01

    Full Text Available Abhishek A Solanki,1 Daniel T Chang,2 Stanley L Liauw11Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA; 2Department of Radiation Oncology, Stanford University, Stanford, CA, USAAbstract: Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT, followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision. Approximately 15% of patients can have a pathologic complete response (pCR at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT.Keywords: rectal cancer, chemoradiotherapy, total mesorectal excision, nonoperative management, organ preservation

  19. Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: a decision analysis.

    Science.gov (United States)

    Prica, Anca; Chan, Kelvin; Cheung, Matthew C

    2012-09-01

    In immunocompetent patients with primary central nervous system (CNS) lymphoma, combined modality therapy (CMT) using high-dose methotrexate and whole brain radiotherapy has improved response rates compared to chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity. A Markov decision-analytic model compared CMT to chemotherapy alone in patients with primary CNS lymphoma. Baseline probabilities were derived from a systematic literature review. Outcomes were life expectancy and quality-adjusted life expectancy. Sensitivity analyses were performed. The life expectancy was 2·69 years for CMT and 2·77 years for chemotherapy alone. The quality-adjusted life expectancies for the two strategies were 1·70 and 1·67 quality-adjusted life years (QALYs) respectively. In younger patients <60 years of age, CMT yielded a quality-adjusted life expectancy of 2·71 QALYs, compared to 2·09 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0·62 QALYs or 7·4 quality-adjusted months. There was no difference between the strategies in the older group. The model was robust to key variables for the younger group. The preferred induction strategy for younger patients appears to be CMT, maximizing life expectancy, and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone. © 2012 Blackwell Publishing Ltd.

  20. [Remote results of using prostaglandins E1 and immunotherapy in combined modality treatment of various-aetiology trophic ulcers].

    Science.gov (United States)

    Alekhin, D I; Mikhaĭlova, O A; Sumnaia, D B; Dodonov, N P; Baltrushevich, O A

    2010-01-01

    The purpose of this study was to assess short- and long-term efficacy of combined-modality therapy (comprising PGE1-group preparations and immunocorrection) used to treat indolent trophic ulcers in patients presenting with chronic venous insufficiency (CVI) and cutaneous angiitis. Examined herein were both immediate and remote therapeutic outcomes obtained in patients suffering from indolent trophic ulcers secondary to CVI (post-thrombophlebic disease [PTPD] and varicose disease [VD]), as well as ulcers resulting from vasculitis or vasculopathy. The conventional therapy was supplemented with infusion of PGE1-group preparations and immunocorrection. Also investigated were the indices of microcirculation and the immune status, the percentage of the trophic ulcers having healed, the trophic-ulcer recurrence rate in the remote period, feasibility offurther performing a radical surgical intervention, the patients' quality of life after the treatment, and the need for repeat therapeutic courses according to the regimen proposed. The use of PGE1-group preparations in a combination with immunocorrection confirmed high efficacy of the treatment for various-aetiology trophic ulcers (with the preserved arterial blood flow). The trophic ulcers were observed to epithelialize rapidly following the initiation of treatment, thus making it possible to appropriately prepare the patient suffering from varicose disease for further surgical management. The remote-period evidence clearly showed that the use of the proposed therapeutic regimen had eventually led to a considerable improvement in the patients' quality of life, dramatically decreasing the recurrence rate of trophic ulcers in patients with PTPD and vasculopathies, and thus may safely be recommended both for prevention of ulcer relapses and as part of maintaining therapeutic courses. The detected deviations in the immune status of the patients afflicted with vasculitis and those suffering from CVI confirmed the need for

  1. Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

    International Nuclear Information System (INIS)

    Beal, Kathryn; Abrey, Lauren E; Gutin, Philip H

    2011-01-01

    Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

  2. What Modals Are: Modal Verbs, Modal Words, and Auxiliary Modals

    Directory of Open Access Journals (Sweden)

    Fazira A. Kakzhanova

    2013-01-01

    Full Text Available The modals are a complicated grammatical phenomenon. As of today, the status of modals is still not precisely defined in the linguistics literature, and they are described under different names: modal verbs, modal words, auxiliary modals, or defective verbs. Modals express the result of the conversion of thought processes (deep structure about the realization of actions into surface structure. As articles determine the status of nouns as indefinite or definite things, modals determine the relation of a person to actions or the quality of an action as realizable or unrealizable. Modals cannot truly be ‘modal verbs’, because they lack the morphological characteristics of verbs (aspect, voice, mood, and tense, and the term ‘defective verb’ is flawed for the same reason. Furthermore, they cannot be ‘auxiliary modals’, because they don’t neutralize their main meanings when they become auxiliary. Thus, I propose to refer to these elements only as modals or modal words.

  3. [Neuroprotective effects of curcumin].

    Science.gov (United States)

    Li, Yong; Wang, Pengwen

    2009-12-01

    Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

  4. Modal concord

    NARCIS (Netherlands)

    Zeijlstra, H.; Gibson, M.; Friedman, T.

    2008-01-01

    Sentences containing two (or more) modal elements of the same modal type and quantificational force often yield a concord reading, where the semantics of the sentence seems to contain only one modal operator, rather than a cumulative reading. In this paper I have argued that Modal Concord is a

  5. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Vashistha, Vishal [Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Wang, Hanzhang [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Mazzone, Andrew [Rush Medical College, Rush University Medical Center, Chicago, Illinois (United States); Liss, Michael A.; Svatek, Robert S. [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Schleicher, Mary [Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Kaushik, Dharam, E-mail: Kaushik@uthscsa.edu [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2017-04-01

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

  6. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

    International Nuclear Information System (INIS)

    Vashistha, Vishal; Wang, Hanzhang; Mazzone, Andrew; Liss, Michael A.; Svatek, Robert S.; Schleicher, Mary; Kaushik, Dharam

    2017-01-01

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

  7. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Vashistha, Vishal; Wang, Hanzhang; Mazzone, Andrew; Liss, Michael A; Svatek, Robert S; Schleicher, Mary; Kaushik, Dharam

    2017-04-01

    To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT-radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and ClinicalTrials.gov) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

    Science.gov (United States)

    Jackson, Matthew W; Rusthoven, Chad G; Jones, Bernard L; Kamdar, Manali; Rabinovitch, Rachel

    2016-05-01

    Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared. © 2016 Wiley Periodicals, Inc.

  9. Improving cytotoxicity against cancer cells by chemo-photodynamic combined modalities using silver-graphene quantum dots nanocomposites

    Directory of Open Access Journals (Sweden)

    Habiba K

    2015-12-01

    Full Text Available Khaled Habiba,1,2 Joel Encarnacion-Rosado,2,3 Kenny Garcia-Pabon,2,4 Juan C Villalobos-Santos,2,5 Vladimir I Makarov,1 Javier A Avalos,2,6 Brad R Weiner,2,7,8 Gerardo Morell1,2,7 1Department of Physics, University of Puerto Rico – Rio Piedras Campus, 2Molecular Sciences Research Center, University of Puerto Rico, 3Department of Biology, 4Faculty of Education, University of Puerto Rico – Rio Piedras Campus, San Juan, 5Department of Biology, 6Department of Physics, University of Puerto Rico – Bayamon Campus, Bayamon, 7Institute for Functional Nanomaterials, University of Puerto Rico, 8Department of Chemistry, University of Puerto Rico – Rio Piedras Campus, San Juan, PR, USA Abstract: The combination of chemotherapy and photodynamic therapy has emerged as a promising strategy for cancer therapy due to its synergistic effects. In this work, PEGylated silver nanoparticles decorated with graphene quantum dots (Ag-GQDs were tested as a platform to deliver a chemotherapy drug and a photosensitizer, simultaneously, in chemo-photodynamic therapy against HeLa and DU145 cancer cells in vitro. Ag-GQDs have displayed high efficiency in delivering doxorubicin as a model chemotherapy drug to both cancer cells. The Ag-GQDs exhibited a strong antitumor activity by inducing apoptosis in cancer cells without affecting the viability of normal cells. Moreover, the Ag-GQDs exhibited a cytotoxic effect due to the generation of the reactive singlet oxygen upon 425 nm irradiation, indicating their applicability in photodynamic therapy. In comparison with chemo or photodynamic treatment alone, the combined treatment of Ag-GQDs conjugated with doxorubicin under irradiation with a 425 nm lamp significantly increased the death in DU145 and HeLa. This study suggests Ag-GQDs as a multifunctional and efficient therapeutic system for chemo-photodynamic modalities in cancer therapy. Keywords: multifunctional nanoparticles, silver nanoparticles, cancer therapy, drug

  10. The evaluation of radiation therapy and combined-modality therapy for non-small-cell lung cancer in elderly

    International Nuclear Information System (INIS)

    Yoon, Won Sup; Yang, Dae Sik; Kim, Chul Yong

    2007-01-01

    To compare radiation therapy alone to combined modality therapy about survival rate and tolerance of elderly patients (70 = or ≥) with non-small-cell lung cancer (NSCLC). Between 1998 and 2002, 57 patients given radiation therapy due to NSCLC (Stage III) were analysed retrospectively. Radiation therapy alone (RT), concurrent chemoradiation (CRT), and sequential chemoradiation (SCRT) was done to 33, 16 and 8 patients, respectively. Patient's median age was 74 (range 70 ∼ 85). Male and female are 51 patients and 6 patients, respectively. 23 patients were stage IIIa and 34 were stage IIIb. Patients' characteristic distribution of RT and CRT was not significantly different except mass size that RT has a bigger than CRT. The fraction size of radiation therapy was 1.8 Gy in CRT and 1.8 ∼ 3 Gy in other groups. Total radiation dose was 51 ∼ 63 Gy according to the fraction size. If the prescribed total radiation dose was successfully irradiated, we stated that it was completion of radiation therapy. 52 patients was dead. Median period of radiation therapy was as follow: RT, 35 days, CRT, 60.5 days and SCRT, 35 days. Overall median survival time (MST) was 10.1 months. The 1 yr-and 2 yr-overall survival rate was 39.8% and 17.6%, respectively. MST of RT, CRT and SCRT was 8.9, 8.2 and 11.7 months, respectively. The 1 yr survival rate of RT, CRT and SCRT was 38.4%, 37.5% and 50% (not significant). Patients given incomplete radiation therapy were 12 (RT, 5 CRT, 6 SCRT, 1). N stage (ρ = 0.081) and the difference of treatment methods (ρ = 0.079) were the factors affecting incompletion of radiation therapy, but it was not significant. In case of combined-agents chemotherapy, 4 of 8 ceased radiation therapy. T stage (T ≥ 3), mass size (≥ 5 cm), Karnofsky performance scale (≤ 70) and completion of radiation therapy were the prognostic factors in uni-and multi-variate analysis. In elderly patients wit NSCLC, radiation therapy alone was a treatment method with similar

  11. Neuroprotection in glaucoma

    Directory of Open Access Journals (Sweden)

    Azadeh Doozandeh

    2016-01-01

    Full Text Available Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies. A few agents (such as brimonidine or memantine with neuroprotective effects in experimental studies have advanced to clinical trials; however the results of clinical trials for these agents have not been conclusive. Nevertheless, lack of compelling clinical evidence has not prevented the off-label use of some of these compounds in glaucoma practice. Stem cell transplantation has been reported to halt experimental neurodegenerative disease processes in the absence of cell replacement. It has been hypothesized that transplantation of some types of stem cells activates multiple neuroprotective pathways via secretion of various factors. The advantage of this approach is a prolonged and targeted effect. Important concerns in this field include the secretion of unwanted harmful mediators, graft survival issues and tumorigenesis. Neuroprotection in glaucoma, pharmacologically or by stem cell transplantation, is an interesting subject waiting for broad and multidisciplinary collaborative studies to better clarify its role in clinical practice.

  12. Treatment Outcomes in Very High-risk Prostate Cancer Treated by Dose-escalated and Combined-Modality Radiation Therapy.

    Science.gov (United States)

    Shilkrut, Mark; McLaughlin, Patrick W; Merrick, Gregory S; Vainshtein, Jeffrey M; Hamstra, Daniel A

    2016-04-01

    The aim of this study was to report treatment outcomes in patients with very high-risk prostate cancer (VHRPC) treated with dose-escalated radiotherapy. We conducted a retrospective multi-institutional review on patients with VHRPC (those with at least 2 high-risk factors of prostate-specific antigen >20 ng/mL, Gleason score 8 to 10, or clinical T3 to T4 stage), treated with either dose-escalated external-beam radiotherapy (EBRT) or combined-modality radiotherapy (CMRT) consisting of pelvic irradiation and permanent interstitial brachytherapy. A total of 238 patients with VHRPC were identified. Of them, 69% of patients received EBRT and 31% received CMRT; 88% received androgen-deprivation therapy (ADT), 56% for ≥24 months (long-term ADT). The majority (69%) of patients were above 65 years old and were less likely to receive CMRT than younger patients (25% vs. 43%, P=0.006), although they did not differ from younger patients in tumor characteristics. Median follow-up was 61 months (interquartile range, 38 to 93 mo). Biochemical progression-free survival (BPFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) for all patients at 8 years were (±SE): 50.6%±4.7%, 68.5%±4.3%, 78.7%±3.8%, respectively, and were similar for patients 65 years and below versus above 65 years old (BPFS: HR=0.88, P=0.56; DMFS: HR=0.79, P=0.40; CSS HR=0.99, P=0.99). After adjustment for patient, tumor, and treatment-related covariates on multivariate analysis, CMRT was associated with improved BPFS (HR=0.44, P=0.012) with trends for DMFS (HR=0.52, P=0.10) and CSS (HR=0.55, P=0.21), whereas long-term ADT was independently associated with improved BPFS (HR=0.40, P=0.019), CSS (HR=0.20, P=0.002), and PCSM (HR=0.25, P=0.004). Dose-escalated EBRT or CMRT with long-term ADT resulted in favorable clinical outcomes for patients with VHRPC.

  13. Neuroprotective Mechanisms of Taurine against Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Janet Menzie

    2013-06-01

    Full Text Available Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke.

  14. [A long-term survival case of hepatocellular carcinoma recurrence after the patient received a living donor liver transplantation treated by combined modality therapy].

    Science.gov (United States)

    Hama, Naoki; Marubashi, Shigeru; Dono, Keizo; Kobayashi, Shogo; Kim, Chiwan; Asaoka, Tadafumi; Takeda, Yutaka; Nagano, Hiroaki; Umeshita, Koji; Monden, Morito; Doki, Yuichiro; Mori, Masaki

    2008-11-01

    We report a case of hepatocellular carcinoma (HCC) recurrence after the patient received a living donor liver transplantation, which was treated by combined modality therapy. The patient survived for 67 months. A 61-year-old male was diagnosed as HCC with alcoholic cirrhosis and was transplanted the liver from a living donor. The number of tumors was about 50, the maximum tumor size was 3.3 cm and histology of the tumor was poorly differentiated hepatocellular carcinoma with portal invasion (Vp2). HCC recurred at the peritoneum 12 months after the liver transplantation and was surgically resected. Then, multiple HCC recurred in the liver graft and the patient was treated by systemic chemotherapy, and local therapy such as RFA, PEIT and TAE. Now 67 months after the transplantation, he additionally has a HCC metastasis to the spleen and lung and is treated by combined modality therapy. This case suggested that a combined modality therapy might have improved the survival of the patient after recurrence in the liver transplantation for advanced HCC.

  15. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-30

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

  16. [Retrospective analysis of 856 cases with stage 0 to III rectal cancer underwent curative surgery combined modality therapy].

    Science.gov (United States)

    Chen, Pengju; Yao, Yunfeng; Zhao, Jun; Li, Ming; Peng, Yifan; Zhan, Tiancheng; Du, Changzheng; Wang, Lin; Chen, Nan; Gu, Jin

    2015-07-01

    =0.000, HR=1.349, 95% CI: 1.260 to 1.444) and lymphovascular invasion (P=0.001, HR=1.715, 95% CI: 1.258 to 2.342) are the independent prognostic factors for rectal cancer. Age, surgical approach, differentiation, TNM stage and lymphovascular invasion are independent prognostic factors for rectal cancer. Preoperative evaluation and combined modality therapy can significant reduce the local recurrence and improve overall survival for rectal cancer patients.

  17. Statins: Mechanisms of neuroprotection

    NARCIS (Netherlands)

    van der Most, Peter J.; Dolga, Amalia; Nijholt, Ingrid M.; Luiten, Paul G. M.; Eisel, Ulrich L. M.

    Clinical trials report that the class of drugs known as statins may be neuroprotective in Alzheimer's and Parkinson's disease, and further trials are currently underway to test whether these drugs are also beneficial in multiple sclerosis and acute stroke treatment. Since statins are well tolerated

  18. Breathing, feeding, and neuroprotection

    National Research Council Canada - National Science Library

    Homma, Ikuo; Shioda, S

    2006-01-01

    ... of knowledge of brain functions and morphology. Akiyoshi Hosoyamada, M.D., Ph.D. President Showa University, Tokyo 142-8555, Japan December 2005Preface Brain research is on the march, with several advanced technical developments and new findings uncovered almost daily. Within the brain-research fields, we focus on breathing, neuroprotection, an...

  19. Adenocarcinoma of the esophagus and esophago-gastric junction: The effects of single and combined modalities on the survival and patterns of failure following treatment

    International Nuclear Information System (INIS)

    Whittington, R.; Coia, L.R.; Haller, D.G.; Rubenstein, J.H.; Rosato, E.F.

    1990-01-01

    One hundred sixty-five patients with localized adenocarcinomas of the esophagus or esophago-gastric (EG) junction were treated with surgery alone, radiation therapy alone, chemotherapy alone, surgery followed by post-operative radiation therapy, chemotherapy, or chemosensitized radiation therapy, and chemosensitized radiation therapy alone. Patients were retrospectively evaluated for survival, control of tumor within the mediastinum, post-operative swallowing function, patterns of failure, and treatment-related morbidity. Follow-up of survivors ranges from 9-88 months (median 23 months). Chemotherapy and radiation therapy as single modalities were associated with a recurrence rate of 100%. Combined modality therapy significantly reduced the risk of local recurrence in all patient groups. Chemosensitized radiation therapy alone reduced the local recurrence rate to 48%, and surgery followed by radiation therapy reduced the local failure rate to 24%. When chemotherapy or chemosensitization was added to surgery plus radiation, the risk was further reduced to 15%. The use of combined modality therapy was also found to extend the survival of patients without excessive toxicity. Median survival was shortest among the group treated with radiation alone (5 months) and intermediate among patients following chemosensitized radiation alone (10 months) or complete surgical resection alone (15 months). Patients treated with all three modalities had the longest median survival (21 months). Based on this experience, the optimum treatment of these patients appears to include aggressive attempts at surgical resection with chemosensitized radiation therapy. Excellent pallination can also be achieved in unresectable patients with chemosensitized radiation therapy with a smaller chance for long term survival

  20. The Progressive in Modal Semantics.

    Science.gov (United States)

    Portner, Paul

    1998-01-01

    Presents a semantic analysis of English progressive as an intentional operator within the framework of modal semantics. The treatment allows a combination of the central idea that the progressive's meaning has a major modal component with insights of other theories. Using a more sophisticated background theory of modality allows natural solutions…

  1. The Influence of Patient-related Constutional and Environmental Factors on Early Results of a Combined Modality Therapy of Esophageal Cancer.

    Science.gov (United States)

    Pudło, Kamil; Błotniak, Alan; Skoczylas, Tomasz; Dąbrowski, Andrzej; Szawłowski, Andrzej; Kozłowski, Mirosław; Lampe, Paweł; Wallner, Grzegorz

    2016-10-01

    Among many various factors affecting the outcome of cancer treatment one can distinguish patient, tumor- and treatment-related factors. The association of patient-related factors and results of a combined modality therapy of esophageal cancer has not been extensively explored. The aim of the study was to analyze the impact of patient-related constitutional and environmental factors on early results of combined modality therapy of esophageal squamous cell carcinoma. We retrospectively analyzed prospectively collected data of 84 patients with esophageal cancer randomly assigned to a combined modality treatment. We evaluated the relationship between early outcome of neoadjuvant therapy (overall toxic events, serious toxic events, treatment-related mortality, clinical and pathological response to the treatment) or surgical treatment (postoperative morbidity, mortality and curative resections - R0) and constitutional (age, gender, height, body mass index, Karnofski Performance Status - KPS, blood type) or environmental (inhabitation, smoking duration and intensity, frequency and amount of alcohol consumption and occupational exposure) patient-related factors. Significantly more neoadjuvant therapy related deaths were found in patients with KPS 70-80 (p=0.0016). Interestingly, significantly more toxic events (p=0.0034) after neoadjuvant therapy and a higher postoperative morbidity rate (p=0.0293) were observed in nonsmokers. Similarly, significantly more toxic events (p=0.0029) after neoadjuvant therapy and a higher postoperative mortality rate (p=0.0405) were found in light drinkers. Smoking and consumption of excessive amount of alcohol may attenuate toxic effect of neoadiuvant and surgical therapy in patients treated due to esophageal cancer. The information regarding the mentioned above addictions should not result in giving up an attempt to provide a curative treatment.

  2. Refocusing Neuroprotection in Cerebral Reperfusion Era: New Challenges and Strategies

    Directory of Open Access Journals (Sweden)

    Xiao-Yi Xiong

    2018-04-01

    Full Text Available Pathophysiological processes of stroke have revealed that the damaged brain should be considered as an integral structure to be protected. However, promising neuroprotective drugs have failed when translated to clinical trials. In this review, we evaluated previous studies of neuroprotection and found that unsound patient selection and evaluation methods, single-target treatments, etc., without cerebral revascularization may be major reasons of failed neuroprotective strategies. Fortunately, this may be reversed by recent advances that provide increased revascularization with increased availability of endovascular procedures. However, the current improved effects of endovascular therapy are not able to match to the higher rate of revascularization, which may be ascribed to cerebral ischemia/reperfusion injury and lacking of neuroprotection. Accordingly, we suggest various research strategies to improve the lower therapeutic efficacy for ischemic stroke treatment: (1 multitarget neuroprotectant combinative therapy (cocktail therapy should be investigated and performed based on revascularization; (2 and more efforts should be dedicated to shifting research emphasis to establish recirculation, increasing functional collateral circulation and elucidating brain–blood barrier damage mechanisms to reduce hemorrhagic transformation. Therefore, we propose that a comprehensive neuroprotective strategy before and after the endovascular treatment may speed progress toward improving neuroprotection after stroke to protect against brain injury.

  3. Assessment of the therapeutic aspect of systemic non-biologic anti-psoriatic treatment modalities used in combination with methotrexate

    Directory of Open Access Journals (Sweden)

    Kamran Balighi

    2016-01-01

    Full Text Available Introduction: Psoriasis is a common skin disease affecting 1% to 3% of the population worldwide. Combination therapy with traditional systemic anti-psoriatic agents offers a promising method for managing severe or recalcitrant psoriasis. Aims and Objectives: Lack of documented data regarding the efficacy and safety of combination therapy with methotrexate and other anti-psoriatic drugs in Iranian patients prompted us to design a study to investigate this issue in an Iranian educational hospital. Materials and Methods: Records of psoriatic patients in Razi Hospital were reviewed retrospectively from October 2008 to March 2012. Forty-six patients who had received methotrexate in combination with other systemic anti-psoriatic agents were included in this study. Response to treatment was evaluated by PASI. Adverse reactions and the type of combination were recorded for all patients. Results: Methotrexate was most frequently administered in combination with acitretin (n = 21 followed by cyclosporine (n = 11, and NB-UVB and PUVA (n = 6. Combinations were effective in the majority of patients; 46% showed good response (21 patients, 26% showed moderate response (12 patients and 28% (13 patients showed poor response who therefore switched to another treatment. The treatments were generally tolerable. Thirty-two patients experienced adverse events although none was severe or required hospitalization. The relative frequencies of adverse reactions were different among groups of patients receiving various therapeutic regimens. Conclusions: Methotrexate-combination therapy can offer an effective therapeutic regimen. However, the patients should be monitored for potential adverse effects. More studies are needed to determine the long-term safety and efficacy of these combinations.

  4. Diagnostic role of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for early and atypical bone metastases.

    Science.gov (United States)

    Chen, Xiao-Liang; Li, Qian; Cao, Lin; Jiang, Shi-Xi

    2014-01-01

    The bone metastasis appeared early before the bone imaging for most of the above patients. (99)Tc(m)-MDP ((99)Tc(m) marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi (99)Tc(m)-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.

  5. The long term follow-up of early stage follicular lymphoma treated with radiotherapy, chemotherapy or combined modality treatment.

    Science.gov (United States)

    Sancho, Juan-Manuel; García, Olga; Mercadal, Santiago; Pomares, Helena; Fernández-Alvarez, Rubén; González-Barca, Eva; Tapia, Gustavo; González-García, Esther; Moreno, Miriam; Domingo-Domènech, Eva; Sorigué, Marc; Navarro, José-Tomás; Motlló, Cristina; Fernández-de-Sevilla, Alberto; Feliu, Evarist; Ribera, Josep-Maria

    2015-08-01

    Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observation). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p=0.179), and 37% (40/107) of patients in complete response relapsed (RT 42%, COMBINED 27%, CHEMO 41%, p=0.371). Progression-free survival (PFS) and overall survival (OS) probabilities at 10 years were similar in RT, COMBINED and CHEMO patients (PFS 41%, 61% and 39% [p=0.167], and OS 77%, 81% and 72% [p=0.821], respectively), while the COMBINED group showed a trend to better time-to-progression (TTP 43%, 72% and 47% [p=0.055]). On multivariate analysis, only a FLIPI score ≥2 showed a trend to influence PFS (HR 2.1 [95% confidence interval 0.9-4.6], p=0.067), and OS (HR 2.4 [0.9-6.5], p=0.084), while patients treated with radiotherapy plus chemotherapy (COMBINED group) showed a significantly better TTP compared with those receiving only RT (HR 0.3 [0.1-0.8], p=0.024). In our study no benefit was observed in survival with the use of systemic therapy compared with local radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The Promise of Neuroprotective Agents in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Judith ePotashkin

    2011-11-01

    Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

  7. Treatment-related fractures after combined modality therapy for soft tissue sarcomas of the proximal lower extremity: Can the risk be mitigated?

    Science.gov (United States)

    Bishop, Andrew J; Zagars, Gunar K; Allen, Pamela K; Moon, Bryan S; Lin, Patrick P; Lewis, Valerae O; Guadagnolo, B Ashleigh

    2016-01-01

    The purpose of this study was to investigate the incidence of and risk factors associated with femur fracture after combined modality therapy for soft tissue sarcomas (STS) of the proximal lower extremity. We reviewed the records of 596 patients with STS of the proximal lower extremity consecutively treated with surgery and radiation therapy (RT) from 1966 to 2012. One hundred ninety-seven patients (33%) received 50 Gy to the entire femur circumference (n = 197, 33%); 265 patients (45%) received perioperative chemotherapy, and during surgery, 155 patients (26%) had bone exposure, whereas 82 patients (14%) had the periosteum stripped. The Kaplan-Meier method was used to estimate actuarial outcome rates, and both Cox regression modeling and competing risk analyses using the method of Fine and Gray were performed. Median follow-up time was 110 months (range, 6-470 months). The actuarial 10-year local control and overall survival rates were 88% (95% confidence interval [CI], 84%-90%) and 62% (95% CI, 57%-66%). Twelve patients had pathologic fractures, which were associated with 50 Gy to the entire bone circumference (P modalities contributes to the overall risk, and a multidisciplinary approach to mitigating fracture risk is needed. Although avoiding circumferential bone coverage with the 50-Gy isodose line may be a valuable dosimetric parameter, more rigorous dosimetric studies are required. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  8. Combination treatment of physical modalities in the treatment of musculoskeletal pain syndromes: a prospective-controlled study

    Directory of Open Access Journals (Sweden)

    Karin Pieber

    2010-12-01

    Full Text Available The aim of the study was to evaluate the effect of combinations of several physical therapies in the treatment of musculoskeletal pain syndromes by a prospective, controlled study. Forty patients (5 men and 35 women, 18-80 years with musculoskeletal pain syndrome were included. Thirty patients were assigned to the intervention group and 10 patients to the control group. The intervention group received a combination of physical therapies according to the clinical needs (electrotherapy, fango packs, mud packs, ultrasound, massage, exercise therapy. Treatment consisted of 10 sessions. The control group did not receive any physical therapy in the waiting period. The intervention group was examined at the beginning and the end of the treatment period. The control group was evaluated at the beginning and the end of the waiting period (before their physical therapy treatment started. Main outcome measurements were: Visual analogue scale for pain (VAS; Timed Get up and Go Test (TUG; Functional Reach Test (FRT. In addition bodily, emotional and social functioning was accessed by selected ICF-Items and items of the SF-36 health survey (SF-36. The main outcome measures showed significant improvement in the intervention group compared to the control group. Furthermore, ICF- and SF-36-Items also improved. In conclusion significant pain relief and improvement of function was achieved by a combination treatment of physical therapies in patients with musculoskeletal pain syndromes.

  9. Dual-Modality Imaging of the Human Finger Joint Systems by Using Combined Multispectral Photoacoustic Computed Tomography and Ultrasound Computed Tomography.

    Science.gov (United States)

    Liu, Yubin; Wang, Yating; Yuan, Zhen

    2016-01-01

    We developed a homemade dual-modality imaging system that combines multispectral photoacoustic computed tomography and ultrasound computed tomography for reconstructing the structural and functional information of human finger joint systems. The fused multispectral photoacoustic-ultrasound computed tomography (MPAUCT) system was examined by the phantom and in vivo experimental tests. The imaging results indicate that the hard tissues such as the bones and the soft tissues including the blood vessels, the tendon, the skins, and the subcutaneous tissues in the finger joints systems can be effectively recovered by using our multimodality MPAUCT system. The developed MPAUCT system is able to provide us with more comprehensive information of the human finger joints, which shows its potential for characterization and diagnosis of bone or joint diseases.

  10. Dual-Modality Imaging of the Human Finger Joint Systems by Using Combined Multispectral Photoacoustic Computed Tomography and Ultrasound Computed Tomography

    Directory of Open Access Journals (Sweden)

    Yubin Liu

    2016-01-01

    Full Text Available We developed a homemade dual-modality imaging system that combines multispectral photoacoustic computed tomography and ultrasound computed tomography for reconstructing the structural and functional information of human finger joint systems. The fused multispectral photoacoustic-ultrasound computed tomography (MPAUCT system was examined by the phantom and in vivo experimental tests. The imaging results indicate that the hard tissues such as the bones and the soft tissues including the blood vessels, the tendon, the skins, and the subcutaneous tissues in the finger joints systems can be effectively recovered by using our multimodality MPAUCT system. The developed MPAUCT system is able to provide us with more comprehensive information of the human finger joints, which shows its potential for characterization and diagnosis of bone or joint diseases.

  11. A case report of successful intraoperative photo- dynamic therapy as the step of combined modality treatment in patient with stage IIIb breast cancer

    Directory of Open Access Journals (Sweden)

    E. К. Saribekyan

    2013-01-01

    Full Text Available The case of successful combined modality treatment in patient with stage IIIB T4bN1M0 breast cancer is reported. The first step included 2 courses of neoadjuvant polychemotherapy in CAF regimen with decrease of tumor size. The second step was irradiation (total dose of 45 Gy of breast and areas of regional metastasis. The third step was radical mastectomy by Madden with polypositional intraoperative photodynamic therapy with photosens (the output laser power 1500 mW, light dose 30 J/cm2, total time of irradiation – 25.6 min. The histological study of surgical specimen showed infiltrative ductal carcinoma with metastases in 3 nodes without fat invasion. In the post-operative period the patient had 3 courses of adjuvant chemotherapy in CAF regimen. Currently the duration of recurrence-free survival after treatment is 4 years. 

  12. Ghost cell odontogenic carcinoma with suspected cholesterol granuloma of the maxillary sinus in a patient treated with combined modality therapy: A case report and the review of literature.

    Science.gov (United States)

    Qin, You; Lu, Yanwei; Zheng, Liduan; Liu, Hong

    2018-02-01

    Ghost cell odontogenic carcinoma (GCOC) is a rare malignant odontogenic tumor with aggressive growth characteristics. A 41-year-old Chinese male visited our hospital in 2013, with a 4-month history of bloody purulent rhinorrhea with a peculiar smell in the right nasal cavity. The patient suffered from recurrent GCOC with suspected cholesterol granuloma of the maxillary sinus. The patient was incorrectly diagnosed with a calcifying epithelial odontogenic tumor at his first recurrence. Physical examination, radiological examination, and histopathology were used to identify GCOC. Considering the recurrence of GCOC and poor effects of single surgery, postoperative adjuvant chemotherapy and concurrent chemoradiotherapy were performed after radical surgical excision. So far, no significant evidence has suggested recurrence or metastasis after a long-term follow-up. We advocate wide surgery with clean margins at the first accurate diagnosis. Combined modality therapy could be taken for the recurrent GCOC. We expect to provide a new treatment strategy to prevent the growth of this neoplasm.

  13. [A case of advanced gastric cancer diagnosed as stage IV responding to combined modality therapy and surviving for a long duration].

    Science.gov (United States)

    Shimada, Masanari; Murakami, Nozomu; Tanada, Yasuko; Endo, Naoki; Kadoya, Shinichi; Yamada, Tetsuji; Kurumatani, Hiroshi; Doyama, Hisashi

    2013-05-01

    A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.

  14. [A Case of Locally Advanced Thoracic Esophageal Cancer with Larynx Preservation and Curative Resection via Combined Modality Therapy].

    Science.gov (United States)

    Iwama, Mitsuru; Kimura, Yutaka; Shiraishi, Osamu; Kato, Hiroaki; Hiraki, Yoko; Tanaka, Yumiko; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

    2017-11-01

    Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

  15. [Approximately four years of survival benefits for a case of gastric cancer postoperative carcinomatous peritonitis by combined modality therapy].

    Science.gov (United States)

    Katayama, Kazuhisa; Nishino, Takashi; Takahashi, Yuji; Tanaka, Takashi; Okitsu, Hiroshi; Okitsu, Natsu

    2013-05-01

    Carcinomatous peritonitis may develop after operation for gastric cancer. As ascites are difficult to control, especially for gastric cancer postoperative carcinomatous peritonitis, many cases are difficult to treat. The present case was a female patient with carcinomatous peritonitis that occurred 2 years post-surgery. Administration of docetaxel (DOC)and S-1 combination therapy achieved a complete response. However, she had a relapse of carcinomatous peritonitis 3 years post-surgery. She underwent bypass operation, followed by DOC and S-1 combination therapy again. She achieved a good quality of life for more than two years. As side effects in patients worsen with the repeated exposure to chemotherapy, continuing the same treatment is difficult. Therefore, we changed the therapy method to irinotecan(CPT-11)/cisplatin(CDDP)therapy, weekly paclitaxel(PTX)and methotrexate(MTX)/5-fluorouracil(5-FU)therapy, and bypass operation when necessary. Rapid progression of her condition was sequentially suppressed, allowing her to continue her everyday life. Overall, this treatment method provided survival benefits of approximately four years following the recurrence of carcinomatous peritonitis.

  16. Ipsilateral lung dose volume parameters predict radiation pneumonitis in addition to classical dose volume parameters in locally advanced NSCLC treated with combined modality therapy

    Directory of Open Access Journals (Sweden)

    Sushma Agrawal

    2014-01-01

    Full Text Available Purpose: The purpose was to determine the correlation of clinical factors and lung dose volume parameters with significant radiation pneumonitis (RP in non-small cell lung cancer patients treated with combined modality therapy. Materials and Methods: Between January 2008 and December 2010, 52 patients of non-small cell lung cancer were treated with combined modality therapy with radical intent. Radiation pneumonitis was correlated with ipsilateral (V 20 ipsi, V 5 ipsi and MLD ipsi and whole lung (V 20 , V 5 , and MLD dose volume parameters. Clinical factors like pulmonary function tests (PFT, site of tumor, planning target volume, and type of treatment were also correlated with incidence of significant pneumonitis. Results: Out of 52 patients, 35.3% developed grade 2 or more pneumonitis. On univariate analysis, factors significantly correlating with radiation pneumonitis were V 5 (P = 0.002, V 5 ipsi (P = 0.000, V 20 (P = 0.019, V 20 ipsi (P = 0.004, MLD (P = 0.008 and MLD ipsi (P = 0.008. On multivariate analysis, V 5 ipsi was retained as the most significant factor. Concurrent chemoradiation caused significantly more RP than neoadjuvant chemoradiation (P = 0.004. A cutoff of 65% for V 5 ipsi had a sensitivity of 65% and a specificity of 91%. Conclusion: The correlation between pneumonitis and dosimetric constraints has been validated. Adding ipsilateral V 20 , V 5 , and MLD to the classical total lung constraints identifies patients likely to develop pulmonary toxicity in patients undergoing chemoradiation.

  17. Combined-Modality Therapy With Radiation and Chemotherapy for Elderly Patients With Glioblastoma in the Temozolomide Era: A National Cancer Database Analysis.

    Science.gov (United States)

    Rusthoven, Chad G; Koshy, Matthew; Sher, David J; Ney, Douglas E; Gaspar, Laurie E; Jones, Bernard L; Karam, Sana D; Amini, Arya; Ormond, D Ryan; Youssef, A Samy; Kavanagh, Brian D

    2016-07-01

    The optimal management for elderly patients with glioblastoma (GBM) is controversial. Following maximal safe resection or biopsy, accepted treatment paradigms for elderly patients with GBM include combined-modality therapy (CMT) with both radiotherapy (RT) and chemotherapy (CT), RT alone, and CT alone. To evaluate the overall survival (OS) outcomes associated with RT, CT, and CMT for elderly patients with GBM in the modern temozolomide era. In this retrospective cohort study of a prospectively maintained, multi-institutional national cancer registry, the National Cancer Database was queried for elderly patients (≥65 years) with newly diagnosed GBM from January 1, 2005, through December 31, 2011, with complete data sets for RT, CT, tumor resection, Charlson-Deyo comorbidity scores, age, sex, and year of diagnosis. Data analysis was performed from October 2015 through December 2015. Combined-modality therapy, RT, CT. Survival by treatment cohort was estimated using the Kaplan-Meier method and analyzed using the log rank test, univariate and multivariate Cox models, and propensity score-matched analyses. A total of 16 717 patients (median [range] age, 73 [65-≥90 y]; 8870 [53%] male) were identified. The median OS by treatment was 9.0 (95% CI, 8.8-9.3) months with CMT (8435 patients), 4.7 (95% CI, 4.5-5.0) months with RT alone (1693 patients), 4.3 (95% CI, 4.0-4.7) months with CT alone (1018 patients), and 2.8 (95% CI, 2.8-2.9) months with no therapy (5571 patients) (P therapy for elderly patients with GBM, OS was superior with CMT compared with CT alone and RT alone. Survival was similar between CT alone and RT alone, and both CT alone and RT alone were superior to no therapy. This analysis supports the use of CMT for suitable elderly candidates.

  18. Modal Indicators for Operational Modal Identification

    DEFF Research Database (Denmark)

    Zhang, L.; Brincker, Rune; Andersen, P.

    2001-01-01

    modes become more significant than in traditional modal analysis. The two major modal indicators, i.e. Modal Confidence Factor (MCF) and Modal Amplitude Coherence (MAmC) are extended to two-stage time domain modal identification algorithms, together with a newly developed indicator, named as Modal...

  19. [A case of long-term survival due to combined modality therapy for liver metastasis of colon cancer].

    Science.gov (United States)

    Hasegawa, Hirofumi; Hashimoto, Takashi; Nakamura, Toshihiko; Kitagawa, Masaru; Kudo, Kensuke; Shoji, Fumihiro; Kabashima, Akira; Teramoto, Seiichi; Kitamura, Masayuki

    2012-11-01

    The patient was a 68-year-old man. Because sigmoid colon cancer and metastatic liver cancer was diagnosed in August 2009, an indwelling central venous port and sigmoid colon resection were implemented. The metastatic liver cancer was a huge tumor occupying the right hepatic lobe and caudate lobe. In consideration of the risk associated with the resection and the possibility of early recurrence, the postoperative chemotherapy was selected. He underwent 9 courses of bevacizumab (Bev)+FOLFOX. The tumor was observed to reduce but continued to occupy the right lobe and caudate lobe. At this point, the surgical treatment was selected because the tumor has been shrunk and there is no appearance of new metastases. In order to preserve residual liver function, he underwent percutaneous transhepatic portal embolization and then resection of the right lobe of the liver in February 2010. Although the Bev+FOLFOX treatment was started again after surgery as adjuvant chemotherapy, the metastatic liver cancer recurred in the remnant liver in August 2010. Because it was about 6 months from the first recurrence of liver resection, we decided to continue chemotherapy immediately without resection. However, the chemotherapy was insufficient to shrink the tumor, which increased because it was present at 3 locations in the liver. Therefore, partial hepatectomy at the 3 locations with positron-emission tomography was performed in February 2011. Since then, chemotherapy has not been performed in patients, and there is no recurrence as of March 2012. In the guideline for the treatment of liver metastasis of colorectal cancer, even though chemotherapy is currently developed, the surgical procedure is recommended for patients who are responsive to local therapy. If the cancer recur immediately after resection, it is difficult to decide whether to re-resect. We report the case in which the tumor-free status can be observed as a result of a combination of systemic chemotherapy and local

  20. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Flampouri, Stella [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Zaiden, Robert [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Slayton, William [Department of Pediatrics, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Sandler, Eric [Department of Pediatrics, Division of Hematology/Oncology Nemours Children' s Clinic, Jacksonville, Florida (United States); Ozdemir, Savas [Department of Radiology, Division of Functional and Molecular Imaging, University of Florida College of Medicine, Jacksonville, Florida (United States); Dang, Nam H.; Lynch, James W. [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P. [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

    2014-08-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

  1. Involved-node proton therapy in combined modality therapy for Hodgkin lymphoma: results of a phase 2 study.

    Science.gov (United States)

    Hoppe, Bradford S; Flampouri, Stella; Zaiden, Robert; Slayton, William; Sandler, Eric; Ozdemir, Savas; Dang, Nam H; Lynch, James W; Li, Zuofeng; Morris, Christopher G; Mendenhall, Nancy P

    2014-08-01

    This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy. Copyright

  2. Population-based estimates of survival benefit associated with combined modality therapy in elderly patients with locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Davidoff, Amy J; Gardner, James F; Seal, Brian; Edelman, Martin J

    2011-05-01

    Combined modality therapy (CMT; radiation and chemotherapy) is indicated for fit, elderly patients with inoperable, locally advanced non-small cell lung cancer. We used population level data to examine effects of CMT on survival. Medicare patients who are 66 years or older with locally advanced non-small cell lung cancer (stages IIIA and IIIB without pleural effusion) from 1997 to 2002 were identified in Surveillance Epidemiology and End Results-Medicare. Detailed insurance claims were used to characterize treatment modality (none, chemotherapy only, radiotherapy only [XRT-ONLY], or CMT). CMT was further categorized as sequential (CMT-SEQ), or concurrent chemoradiation alone (CMT-ONLY), with induction (CMT-IND), or with consolidation chemotherapy (CMT-CON). Nonparametric models estimated survival effects of treatment regimens, controlling for patient characteristics, including claims-based indicators of performance status. Propensity score analysis adjusted for treatment selection. Of the 6325 patients, 66% received therapy, with 41% (N = 1745) receiving XRT-ONLY and 45% (N = 1909) receiving CMT (12.5% CMT-SEQ, 35.3% CMT-ONLY, 11.3% CMT-IND, and 20.3% with CMT-CON). CMT had a survival benefit relative to XRT-ONLY (hazard ratio: 0.782, 95% confidence interval: 0.750-0.816; additional 4.4 months median survival; adjusted 10.7% increase in 1-year survival). Relative to CMT-SEQ, concurrent CMT-ONLY was associated with an increased mortality risk, whereas CMT-IND regimens provided a survival benefit (hazard ratio: 0.731, 95% confidence interval: 0.600-0.891; additional 3.8 months; and adjusted 14.4% increase in 1-year survival). Survival benefits associated with CMT in clinical trials can extend to the elderly in routine care settings. CMT-ONLY is associated with the greatest mortality risk, suggesting that more gradual strategies (CMT-IND) may be more appropriate for the elderly population.

  3. Neuroprotective Properties of the Marine Carotenoid Astaxanthin and Omega-3 Fatty Acids, and Perspectives for the Natural Combination of Both in Krill Oil

    Directory of Open Access Journals (Sweden)

    Marcelo P. Barros

    2014-03-01

    Full Text Available The consumption of marine fishes and general seafood has long been recommended by several medical authorities as a long-term nutritional intervention to preserve mental health, hinder neurodegenerative processes, and sustain cognitive capacities in humans. Most of the neurological benefits provided by frequent seafood consumption comes from adequate uptake of omega-3 and omega-6 polyunsaturated fatty acids, n-3/n-6 PUFAs, and antioxidants. Optimal n-3/n-6 PUFAs ratios allow efficient inflammatory responses that prevent the initiation and progression of many neurological disorders. Moreover, interesting in vivo and clinical studies with the marine antioxidant carotenoid astaxanthin (present in salmon, shrimp, and lobster have shown promising results against free radical-promoted neurodegenerative processes and cognition loss. This review presents the state-of-the-art applications of n-3/n-6 PUFAs and astaxanthin as nutraceuticals against neurodegenerative diseases associated with exacerbated oxidative stress in CNS. The fundamental “neurohormesis” principle is discussed throughout this paper. Finally, new perspectives for the application of a natural combination of the aforementioned anti-inflammatory and antioxidant agents (found in krill oil are also presented herewith.

  4. Comparative evaluation of efficacy of three treatment modalities – tetracycline fibers, scaling and root planing, and combination therapy: A clinical study

    Directory of Open Access Journals (Sweden)

    Aashima Bajaj Dang

    2016-01-01

    Full Text Available Background: Tetracycline is one of the primary antibiotics prescribed for antimicrobial therapy in periodontics. It has a broad spectrum of activity being effective against most bacteria as well as spirochetes. Due to limitations of systemic drug therapy, recent formulations of the drug for local administration in the subgingival area have been introduced, including collagen fibers impregnated with tetracycline. Aims and Objective: To compare the effectiveness of tetracycline fibers alone or in combination with scaling and root planing (SRP on clinical parameters in chronic periodontitis patients. Materials and Methods: A total of twenty patients comprising of both sexes in the age group of 35-60 years with chronic periodontitis were selected. Split-mouth design was used, and three teeth from each patient with periodontal pocket measuring > 5 mm were selected which were treated with different treatment modality. They were randomly divided into site A (SRP, site B (tetracycline fibers only, and site C (combination therapy. Clinical parameters of plaque index (PI, gingival index (GI, pocket probing depth, and clinical attachment level (CAL were recorded at 0, 30, and 45 days. The data obtained was compiled and put to statistical analysis. Results: All the three groups showed improvement in PI, GI, probing pocket depth, and CAL. Results of the study showed greater improvements in clinical parameters in Group C compared to Group A and Group B. Conclusion: The results indicate that the adjunctive use of tetracycline fibers with SRP is a clinically effective and simple nonsurgical treatment method to improve periodontal health.

  5. Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin’s lymphoma

    International Nuclear Information System (INIS)

    Verhappen, Marieke H.; Poortmans, Philip M.P.; Raaijmakers, Esther; Raemaekers, John M.M.

    2013-01-01

    Background and purpose: This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL. Patients and methods: We included 258 patients with stage I/II aggressive NHL who received combined modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose of 30–40 Gy in 15–20 fractions IFRT or INRT. We compared survival, relapse pattern, radiation-related toxicity and quality of life for both RT techniques. Results: Type of RT was not related to the outcome in either the uni- or multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of which 47 (80%) were documented as distant recurrence only. Failure of the INRT technique was noted in one patient. There was no significant difference in acute radiation-related toxicity between RT-groups but IFRT showed a significantly higher incidence of higher grade toxicities. Patients treated with INRT had a significantly better physical functioning and global quality of life compared to the IFRT group. Conclusions: Given the retrospective nature of this study, no solid conclusions can be drawn. However, in view of the equivalent efficacy and more favorable toxicity profile, the replacement of IFRT by INRT in combination with chemo-(immuno)-therapy looks very attractive for patients with early stage aggressive NHL

  6. Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin's lymphoma.

    Science.gov (United States)

    Verhappen, Marieke H; Poortmans, Philip M P; Raaijmakers, Esther; Raemaekers, John M M

    2013-10-01

    This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL. We included 258 patients with stage I/II aggressive NHL who received combined modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose of 30-40 Gy in 15-20 fractions IFRT or INRT. We compared survival, relapse pattern, radiation-related toxicity and quality of life for both RT techniques. Type of RT was not related to the outcome in either the uni- or multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of which 47 (80%) were documented as distant recurrence only. Failure of the INRT technique was noted in one patient. There was no significant difference in acute radiation-related toxicity between RT-groups but IFRT showed a significantly higher incidence of higher grade toxicities. Patients treated with INRT had a significantly better physical functioning and global quality of life compared to the IFRT group. Given the retrospective nature of this study, no solid conclusions can be drawn. However, in view of the equivalent efficacy and more favorable toxicity profile, the replacement of IFRT by INRT in combination with chemo-(immuno)-therapy looks very attractive for patients with early stage aggressive NHL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Neuroprotection by flavonoids

    Directory of Open Access Journals (Sweden)

    Dajas F.

    2003-01-01

    Full Text Available The high morbidity, high socioeconomic costs and lack of specific treatments are key factors that define the relevance of brain pathology for human health and the importance of research on neuronal protective agents. Epidemiological studies have shown beneficial effects of flavonoids on arteriosclerosis-related pathology in general and neurodegeneration in particular. Flavonoids can protect the brain by their ability to modulate intracellular signals promoting cellular survival. Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin showed a marked cytoprotective capacity in in vitro experimental conditions in models of predominantly apoptotic death such as that induced by medium concentrations (200 µM of H2O2 added to PC12 cells in culture. Nevertheless, quercetin did not protect substantia nigra neurons in vivo from an oxidative insult (6-hydroxydopamine, probably due to difficulties in crossing the blood-brain barrier. On the other hand, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that preparations that help to cross the blood-brain barrier may be critical for the expression of the effects of flavonoids on the brain. The hypothesis is advanced that a group of quercetin-related flavonoids could become lead molecules for the development of neuroprotective compounds with multitarget anti-ischemic effects.

  8. [Multidisciplinary treatment of leptomeningeal metastasis in patients with lung adenocarcinoma: the triple modality combination of EGFR-TKI, VP shunt and irradiation].

    Science.gov (United States)

    Mitsuya, Koichi; Nakasu, Yoko; Mizokami, Yoshihito; Takahashi, Toshiaki; Nakamura, Yukiko; Ono, Akira; Toda, Yoko; Yamamoto, Nobuyuki; Harada, Hideyuki; Nishimura, Tetsuo

    2012-06-01

    Leptomeningeal metastasis (LM) is a devastating complication of systemic cancers. New therapies that have beneficial effects on primary cancers outside the central nervous system (CNS) have underscored the significance of LM. Intrathecal chemotherapy plus radiation therapy are less effective for LM from lung adenocarcinoma. We retrospectively studied outcomes of patients with LM from lung adenocarcinoma who underwent multidisciplinary treatments in our institute. Four patients with LM from lung adenocarcinoma treated with EGFR-TKI, VP shunt and irradiation. Of those four, two presented with increased intracranial pressure, one with epilepsy, and the other with truncal ataxia. Treatment was indicated when LM was confirmed by MR images or cytology, and Karnofsky Performance Status scale was more than 40%, and life expectancy was more than three months if LM was controlled. EGFR mutation was not examined, because of the unsettled approval of Japanese public health insurance at the time of this study. The patients selected for treatment by EGFR-TKI were all Asian women who had never smoked. Treatment sequence was based on clinical symptoms depending on the individual situation. The mean time from diagnosis of lung adenocarcinoma to LM onset was 28 (24 to 36) months. Mean survival time from LM diagnosis was 9 months. All patients died of LM. No patients suffered from peritoneal carcinomatosis or infection after VP shunt. The triple modality combination of EGFR-TKI, VP shunt and radiation therapy may improve outcomes and symptoms of patients with LM from lung adenocarcinoma.

  9. Radiation, chemotherapy or combined modality therapy in adjuvant treatment for stage III endometrial carcinoma in lower southern Thailand: disease recurrence and overall survival.

    Science.gov (United States)

    Pichatechaiyoot, Aroontorn; Buhachat, Rakchai; Boonyapipat, Sathana; Kanjanapradit, Kanet

    2014-03-01

    To survey disease-free survival (DFS) and overall survival (OS) of patients with stage III endometrial carcinoma treated with post-operative radiation and/or chemotherapy The medical records of patients with surgical stage III endometrial carcinoma, and receiving adjuvant treatment between January 2003 and December 2012 were reviewed DFS and OS were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Of the 54 eligible patients, 61% underwent radiation, 19% chemotherapy, and 20% chemotherapy with radiation. The median DFS was 36.7 months. The 3-year DFS and OS was 51.9% (95% CI 36.3-74.1%) and 70.6% (95% CI 57.4-86.8%), respectively. There was no significant difference in DFS and OS among treatment groups. Cox regression analysis showed grade 2-3 tumors and menopause were associated with poor DFS and OS. The DFS and OS in stage III endometrial carcinoma receiving postoperative adjuvant therapy were quite good and were not different among radiation therapy, chemotherapy, and combined treatment groups. The multi-center randomized prospective study was needed to determine the standard modality.

  10. [A case of hepatic metastases from colorectal cancer in a long-term survivor undergoing local combined modality therapy for repeated local recurrences].

    Science.gov (United States)

    Kaneko, Jun; Isogai, Jun; Yoshida, Tsuyoshi; Hasegawa, Kumi; Matsui, Toshihiro; Aoyagi, Haruhiko; Maejima, Shizuaki

    2014-11-01

    Herein, we report of a long-term survivor who underwent local combined modality therapy for local hepatic recurrences detected 10 years after initial surgery for colorectal cancer and 7 years after metachronous liver metastasis. In the third year after surgery for colorectal cancer, a solitary liver metastasis was detected, and curative surgical resection was performed. However, because local recurrence developed 3 years later, curative resection was repeated. When local recurrence developed again 1.5 years later, the patient declined surgery and systemic chemotherapy, and radiofrequency ablation was performed. However, because of the development of another local recurrence 6 months later, hepatic arterial infusion chemotherapy was initiated. This therapy has been continued for 1.5 years to date, with successful local disease control and no adverse events. Although surgical resection is the first choice for resectable liver metastases of colorectal cancer, thermocoagulation and hepatic arterial infusion chemotherapy can also be valid options for patients who are inoperable or refuse surgery as well as for those who are not suitable for or refuse systemic chemotherapy. Notwithstanding, the guidelines for the treatment of colorectal cancer (2014 edition) now include the following statement: thermocoagulation is not recommended as an alternative to surgical resection. Hepatic arterial infusion chemotherapy appears to be a promising treatment strategy associated with antitumor effects with few adverse events. It is also relatively less expensive than systemic chemotherapy.

  11. Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: a cost-effectiveness analysis.

    Science.gov (United States)

    Prica, A; Chan, K; Cheung, M

    2014-10-01

    In immunocompetent patients with primary central nervous system lymphoma (PCNSL), combined modality therapy (CMT) using high-dose methotrexate and radiotherapy (WBRT) has improved response rates compared with chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity (NT). A cost-effectiveness analysis using a Markov model compared CMT with chemotherapy alone in age-stratified patients with PCNSL. Baseline probabilities were derived from a systematic literature review. Direct and lost productivity costs were collected from a Canadian perspective and presented in Can$ in 2011. Outcomes were life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. The quality-adjusted life expectancy was 1.55 QALYs for CMT and 1.53 QALYs for chemotherapy alone. In younger patients (aged <60 years), CMT yielded 2.44 QALYs, compared with 1.89 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0.55 QALYs or 6.6 quality-adjusted months. The CMT strategy dominated in younger patients, as it was Can$11 951 less expensive than chemotherapy alone. The chemotherapy-alone strategy dominated in older patients, as it was Can$11 244 less expensive than CMT, and there was no difference in QALYs between the strategies. The model was robust in sensitivity analyses of key variables tested through the plausible ranges obtained from costing sources and published literature. The preferred induction strategy for younger patients with PCNSL appears to be CMT, which minimized cost while maximizing life expectancy and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Interval to biochemical failure predicts clinical outcomes in patients with high-risk prostate cancer treated by combined-modality radiation therapy.

    Science.gov (United States)

    Shilkrut, Mark; McLaughlin, P William; Merrick, Gregory S; Vainshtein, Jeffrey M; Feng, Felix Y; Hamstra, Daniel A

    2013-07-15

    To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, Ptherapy regimen or ADT use. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Laser cellulite treatment and laser-assisted lipoplasty of the thighs and buttocks: Combined modalities for single stage contouring of the lower body.

    Science.gov (United States)

    Petti, Christine; Stoneburner, Jacqueline; McLaughlin, Laura

    2016-01-01

    Cellulite and lipodystrophy are often found together, especially in areas of the buttocks and thighs, causing skin surface irregularities. Each of these conditions is currently treated independently as two separate surgical procedures. In our practice, we developed a novel combined approach for the simultaneous treatment of cellulite and lipodystrophy, as a single stage procedure in the same anatomic area. For the treatment of cellulite, we used the Nd:YAG laser at a wavelength of 1,440-nm, along with an innovative 1,000-micron directional side-firing fiber optic laser system. For the treatment of lipodystrophy, the Nd:YAG laser with a 1,440 nm wavelength, along with a fiber optic laser system was used. The objective of this study is to determine the efficacy and safety of a combined approach for the simultaneous treatment of cellulite and lipodystrophy. In 2012, 16 subjects with noticeable cellulite, Grade II and Grade III, accompanied by mild-to-moderate lipodystrophy of the lower body received single treatments of the Nd:YAG laser at a wavelength of 1,440-nm along with the 1,000-micron side-firing fiber optic laser system for simultaneous treatments of both cellulite and lipodystrophy. Patients were assessed at baseline and 3-6 months post-treatment by a modified Nurnberger-Muller scale utilized to quantify the cellulite severity. Additionally, patient satisfaction and a global aesthetic improvement scale were used to measure the improvement in lipodystrophy. Blinded reviewers identified the correct baseline photographs 97% of the time when presented with a set of photographs. The median modified Nurnberger-Muller scale score at baseline was 4.75 ± 1.2 and the average improvement was 2.0 ± 1.2. Global aesthetic improvement scores ranged from 1 to 3 with an average of 1.58 indicating a much-improved overall appearance. Satisfaction was high for both physicians and patients with scores corresponding to extremely satisfied/satisfied. Precise, effective

  14. Neuroprotection in Glaucoma: A Review

    African Journals Online (AJOL)

    Alasia Datonye

    preventable visual disability, is a progressive neurodegenerative .... Glutamate Excitotoxicity. Oxidative Stress. Protein Misfolding. Awoyesuku E.A, Fiebai B — Neuroprotection in Glaucoma feature of many neurodegenerative diseases, including ... facilitate nascent and stress-induced protein folding and unfolding, and ...

  15. Neuroprotective properties of GLP-1

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Burcelin, Remy; Nathanson, Esther

    2011-01-01

    emptying. Furthermore, data are beginning to emerge that indicate a potential role for GLP-1 in neuroprotection. The increased risk of Alzheimer's disease, Parkinson's disease and stroke in people with type 2 diabetes suggests that shared mechanisms/pathways of cell death, possibly related to insulin...

  16. General anesthetics in children: neurotoxic or neuroprotective?

    Directory of Open Access Journals (Sweden)

    Jéssica Farias Rebouças

    2017-02-01

    Full Text Available Introduction: general anesthetics are involved in neuroprotection in adults after ischemic events and cognitive impairment, thus, they also may be associated with learning disorders in children exposed to them before three years of age. Objective: Describe about the neurotoxic effects of general anesthetics in experimental animals and children. Method: This is a systematic review, performed from search in databases and on PubMed using the keywords "neurotoxicity" and "general anesthetics," and "general anesthetics," "neurotoxicity", "children", "young child "and" pediatric ". Results: The search resulted in 185 articles. Out of these, 78 met our inclusion criteria. We found that there was a significant evidence of neurotoxicity induced by general anesthetics in experimental animals that were just born, resulting in late and permanent cognitive deficits. This effect was associated with multiple exposures, exposure length of time and combination of drugs. However, some studies found cognitive impairment after a single exposure to anesthetic. Conclusion: There is insufficient evidence to state that general anesthetics are neurotoxic and have the potential to trigger learning and behavior disabilities in children. However, we suggest caution in indicating surgery in children under three years old, analyzing risk-benefit and inserting the family in the decision process.   Keywords: Neurotoxicity; Neuroprotection; Cognitive Impairment; Children; General Anesthesics

  17. Interval to Biochemical Failure Predicts Clinical Outcomes in Patients With High-Risk Prostate Cancer Treated by Combined-Modality Radiation Therapy

    International Nuclear Information System (INIS)

    Shilkrut, Mark; McLaughlin, P. William; Merrick, Gregory S.; Vainshtein, Jeffrey M.; Feng, Felix Y.; Hamstra, Daniel A.

    2013-01-01

    Purpose: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). Methods and Materials: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Results: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). Conclusions: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation

  18. Interval to Biochemical Failure Predicts Clinical Outcomes in Patients With High-Risk Prostate Cancer Treated by Combined-Modality Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shilkrut, Mark; McLaughlin, P. William [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States); Merrick, Gregory S. [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, West Virginia (United States); Vainshtein, Jeffrey M.; Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States); Hamstra, Daniel A., E-mail: dhamm@med.umich.edu [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States)

    2013-07-15

    Purpose: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). Methods and Materials: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Results: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). Conclusions: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation

  19. An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma.

    Science.gov (United States)

    Hay, A E; Klimm, B; Chen, B E; Goergen, H; Shepherd, L E; Fuchs, M; Gospodarowicz, M K; Borchmann, P; Connors, J M; Markova, J; Crump, M; Lohri, A; Winter, J N; Dörken, B; Pearcey, R G; Diehl, V; Horning, S J; Eich, H T; Engert, A; Meyer, R M

    2013-12-01

    Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques. Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses. With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects. The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11

  20. Electrical stimulation and tinnitus: neuroplasticity, neuromodulation, neuroprotection.

    Science.gov (United States)

    Abraham, Shulman; Barbara, Goldstein; Arnold, Strashun

    2013-01-01

    Neuroplasticity (NPL), neuromodulation (NM), and neuroprotection (NPT) are ongoing biophysiological processes that are linked together in sensory systems, the goal being the maintenance of a homeostasis of normal sensory function in the central nervous system. It is hypothesized that when the balance between excitatory - inhibitory action is broken in sensory systems, predominantly due to neuromodulatory activity with reduced induced inhibition and excitation predominates, sensory circuits become plastic with adaptation at synaptic levels to environmental inputs(1). Tinnitus an aberrant auditory sensation, for all clinical types, is clinically considered to reflect a failure of NPL, NM, and NPT to maintain normal auditory function at synaptic levels in sensory cortex and projected to downstream levels in the central auditory system in brain and sensorineural elements in ear. Clinically, the tinnitus sensation becomes behaviorally manifest with varying degrees of annoyance, reflecting a principle of sensory physiology that each sensation has components, i.e. sensory, affect/behavior, psychomotor and memory. Modalities of tinnitus therapies, eg instrumentation, pharmacology, surgery, target a particular component of tinnitus, with resultant activation of neuromodulators at multiple neuromodulatory centers in brain and ear. Effective neuromodulation at sensory neuronal synaptic levels results in NPL in sensory cortex, NPT and tinnitus relief. Functional brain imaging, metabolic (PET brain) and electrophysiology quantitative electroencephalography (QEEG) data in a cochlear implant soft failure patient demonstrates what is clinically considered to reflect NPL, NM, NPT. The reader is provided with a rationale for tinnitus diagnosis and treatment, with a focus on ES, reflecting the biology underlying NPL, NM, NPT.

  1. Long-term outcome of combined modality therapy in retroperitoneal and deep-trunk soft-tissue sarcoma: analysis of prognostic factors

    International Nuclear Information System (INIS)

    Youssef, Emad; Fontanesi, James; Mott, Michael; Kraut, Michael; Lucas, David; Mekhael, Hany; Ben-Josef, Edgar

    2002-01-01

    Purpose: To evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival. Methods and Materials: Between January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control. Results: The actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p=0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p=0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs

  2. Combined modality treatment with chemotherapy, radiation therapy, bevacizumab, and erlotinib in patients with locally advanced squamous carcinoma of the head and neck: a phase II trial of the Sarah Cannon oncology research consortium.

    Science.gov (United States)

    Hainsworth, John D; Spigel, David R; Greco, F Anthony; Shipley, Dianna L; Peyton, James; Rubin, Mark; Stipanov, Michael; Meluch, Anthony

    2011-01-01

    : The aim of the study was to evaluate the feasibility and efficacy of adding bevacizumab and erlotinib to concurrent chemoradiation therapy for first-line treatment of patients with locally advanced squamous carcinoma of the head and neck. : Sixty previously untreated patients with squamous carcinoma of the head and neck (36 with oropharyngeal primaries; 83% men; median age, 56 years; 73% stage IV) received induction chemotherapy with 6 weeks of paclitaxel, carboplatin, infusional 5-fluorouracil, and bevacizumab; this treatment was followed by radiation therapy, weekly paclitaxel, bevacizumab, and erlotinib. : After a median follow up of 32 months, the estimated 3-year progression-free and overall survival rates are 71% and 82%, respectively. Sixty-five percent of patients had major responses after induction therapy; after completion of therapy, 95% of patients had either partial or complete response radiographically. As expected, grade 3/4 mucosal toxicity occurred frequently (88%) during combined modality; no unexpected toxicity resulted from the addition of bevacizumab and erlotinib. : The addition of bevacizumab and erlotinib to first-line combined modality therapy was feasible in a community-based setting, producing toxicity comparable to other effective combined modality regimens for head and neck cancer. The high level of efficacy suggests that incorporation of these targeted agents into first-line therapy should be further explored.

  3. Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Zoe eFonseca-Kelly

    2012-05-01

    Full Text Available Resveratrol is a naturally-occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis. In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for multiple sclerosis.

  4. Implementation of the Scanning Laser Doppler Vibrometer Combined with a Light-Weight Pneumatic Artificial Muscle Actuator for the Modal Analysis of a Civil Structure

    Directory of Open Access Journals (Sweden)

    K. Deckers

    2012-01-01

    Full Text Available The identification of the modal parameters of bridges and other large civil constructions has become an important research issue. Different approaches have been proposed depending on the excitation used: ambient excitations (due to wind, traffic, … or artificial excitations (e.g. impact test with heavy drop weights. In practice it turns out that not all modes are well excited by the ambient forces. Hence the application of an artificial actuator is advisable. The problem is that larger constructions often require large and heavy excitation devices, which are hard to manipulate. Another difficulty encountered in performing a modal analysis on large civil constructions is the necessity for a large number of high sensitivity sensors. Consequently a large number of cables has to be installed resulting in a large setup time.

  5. Additive Neuroprotective Effect of Borneol with Mesenchymal Stem Cells on Ischemic Stroke in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Guang Zhang

    2018-01-01

    Full Text Available Intravenous stem cell transplantation initiates neuroprotection related to the secretion of trophic factor. Borneol, a potential herbal neuroprotective agent, is a penetration enhancer. Here, we aimed to investigate whether they have additive neuroprotective effect on cerebral ischemia. Borneol was given to mice by gavage 3 days before middle cerebral artery occlusion (MCAO induction until the day when the mice were sacrificed. Mesenchymal stem cells (MSCs were intravenously injected at 24 h after MCAO induction. Neurological deficits, infarct volume, cell death, and neurogenesis were evaluated. Combined use of MSCs and borneol could more effectively reduce infarction volume and cell apoptosis, enhance neurogenesis, and improve the functional recovery than that of MSCs alone. The findings showed that combined use of borneol and stem cells provided additive neuroprotective effect on cerebral ischemia. However, the supposed effect of borneol on the improved MSC penetration still needs further direct evidence.

  6. Urban Modality

    Directory of Open Access Journals (Sweden)

    Jorge Gil

    2016-02-01

    Full Text Available This thesis proposes a framework for evaluating the mobility potential and performance of urban areas in the city region, as an instrument to support urban development that contributes positively to regional sustainable mobility objectives. The research takes a quantitative approach, modelling and measuring the characteristics of a city-region and of its individual urban areas, in terms of travel patterns and socioeconomic characteristics of the resident population, and in terms of built environment characteristics. It then explores how the built environment defines the affordances of urban areas for travelling by particular modes of transport, i.e. its walk-ability, cycleability, drive-ability and transit-ability, by developing a typology of what I call their ‘urban modality’. And finally the work combines this typology with the socio-economic characteristics of urban areas to determine their sustainable mobility potential and performance. It focuses on the case of the Randstad region of the Netherlands and its VINEX neighbourhoods, which are an emblematic example of new urban areas created under a policy programme with sustainable mobility objectives. A key stance in this work is the understanding that the location of an urban area in the region can be indicative of its population’s travel patterns, because the built environment (infrastructural and socio-economic characteristics are interrelated and present strong regional spatial patterns. What types of urban areas support sustainable travel patterns, and what are their spatial characteristics? How do new neighbourhoods compare to the best performing urban areas, and to other areas of the same ‘modality’ type? These are some of the questions addressed in this study. There are two main contributions of this research: the methods for building and analysing integrated multimodal network models, and the framework for contextual performance evaluation using urban area typologies. The

  7. Modal Epistemology and Conceivability

    DEFF Research Database (Denmark)

    Steffensen, Asger Bo Skjerning

    Philosophical argumentation often depends on modal facts, i.e. facts about what is possible, contingent, or necessary. For thought and cognition outside the domain of philosophy modal facts are also often decisive. It seems we have an easy access to modal facts, but how so? Through a presentation...... of the state-of-the-art in modal epistemology I wish to outline a research project based on conceivability that will try to explain how we come to know modal facts....

  8. A combined modality of carboplatin and photodynamic therapy suppresses epithelial-mesenchymal transition and matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in HEp-2 human laryngeal cancer cells via ROS-mediated inhibition of MEK/ERK signalling pathway.

    Science.gov (United States)

    Mao, Wenjing; Sun, Yan; Zhang, Huankang; Cao, Luhong; Wang, Jiajia; He, Peijie

    2016-11-01

    Photodynamic therapy (PDT) has been developed as a promising treatment modality for laryngeal cancer. 9-Hydroxypheophorbide α (9-HPbD), a novel chlorophyll-derived photosensitizer, has a longer absorption wavelength, which increases the penetration of light to malignant tissues. Carboplatin (CBDCA), a second-generation platinum derivative, also has gained more popularity for the treatment of laryngeal cancer. Our previous studies have elucidated that 9-HPbD-PDT could inhibit the migration and invasion of HEp-2 cells. The objective of this study is to investigate the change of migration and invasion of HEp-2 cells induced by a combined modality of CBDCA and 9-HPbD-PDT in vitro. A wound healing assay, cell migration assay and Matrigel invasion assay were used to evaluate the cellular migration and invasion. Reactive oxygen species (ROS) and Western blots for epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin), MMPs (MMP-2 and MMP-9) and MEK/ERK signalling pathway were performed to investigate the possible mechanisms that may be involved. We observed that CBDCA and 9-HPbD-PDT administration synergistically inhibited the migration and invasion of HEp-2 cells. Moreover, the combined modality cooperatively repressed the EMT process and down-regulated expressions of MMP-2 and MMP-9 via ROS-mediated inhibition of phosphorylation in the MEK/ERK signalling pathway. Our results suggested that the combination of CBDCA and 9-HPbD-PDT might be a promising therapeutic strategy for laryngeal cancer metastasis.

  9. Cross-Modal Semantic Priming.

    Science.gov (United States)

    Tabossi, Patrizia

    1996-01-01

    Describes the cross-modal semantic priming paradigm, including its underlying rationale and the different tasks with which it is combined. Introduces the type of stimuli used and the dependent and independent variables typically manipulated; discusses the paradigm's main advantages and drawbacks; and considers its most important areas of…

  10. Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms

    DEFF Research Database (Denmark)

    Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja

    2017-01-01

    BACKGROUND: Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to m...

  11. Parametric modal transition systems

    DEFF Research Database (Denmark)

    Beneš, Nikola; Křetínský, Jan; Larsen, Kim Guldstrand

    2011-01-01

    in the refinement process like exclusive, conditional and persistent choices. We introduce a new model called parametric modal transition systems (PMTS) together with a general modal refinement notion that overcome many of the limitations and we investigate the computational complexity of modal refinement checking....

  12. Cannabidiol, neuroprotection and neuropsychiatric disorders.

    Science.gov (United States)

    Campos, Alline C; Fogaça, Manoela V; Sonego, Andreza B; Guimarães, Francisco S

    2016-10-01

    Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has possible therapeutic effects over a broad range of neuropsychiatric disorders. CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions. It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors. Moreover, CBD affects synaptic plasticity and facilitates neurogenesis. The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets. In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders. Copyright © 2016. Published by Elsevier Ltd.

  13. An investigation of developmental changes in interpretation and construction of graphic AAC symbol sequences through systematic combination of input and output modalities.

    Science.gov (United States)

    Trudeau, Natacha; Sutton, Ann; Morford, Jill P

    2014-09-01

    While research on spoken language has a long tradition of studying and contrasting language production and comprehension, the study of graphic symbol communication has focused more on production than comprehension. As a result, the relationships between the ability to construct and to interpret graphic symbol sequences are not well understood. This study explored the use of graphic symbol sequences in children without disabilities aged 3;0 to 6;11 (years; months) (n=111). Children took part in nine tasks that systematically varied input and output modalities (speech, action, and graphic symbols). Results show that in 3- and 4-year-olds, attributing meaning to a sequence of symbols was particularly difficult even when the children knew the meaning of each symbol in the sequence. Similarly, while even 3- and 4-year-olds could produce a graphic symbol sequence following a model, transposing a spoken sentence into a graphic sequence was more difficult for them. Representing an action with graphic symbols was difficult even for 5-year-olds. Finally, the ability to comprehend graphic-symbol sequences preceded the ability to produce them. These developmental patterns, as well as memory-related variables, should be taken into account in choosing intervention strategies with young children who use AAC.

  14. Rapamycin/DiR loaded lipid-polyaniline nanoparticles for dual-modal imaging guided enhanced photothermal and antiangiogenic combination therapy.

    Science.gov (United States)

    Wang, Jinping; Guo, Fang; Yu, Meng; Liu, Li; Tan, Fengping; Yan, Ran; Li, Nan

    2016-09-10

    Imaging-guided photothermal therapy (PTT) has promising application for treating tumors. Nevertheless, so far imaging-guided photothermal drug-delivery systems have been developed with limited success for tumor chemo-photothermal therapy. In this study, as the proof-of-concept, a stimuli-responsive tumor-targeting rapamycin/DiR loaded lipid-polyaniline nanoparticle (RDLPNP) for dual-modal imaging-guided enhanced PTT efficacy is reported for the first time. In this system, polyaniline (PANI) with π-π electronic conjugated system and effective photothermal efficiency is chosen as the appropriate model receptor of fluorescence resonance energy transfer (FRET), and loaded cyanine probe (e.g., 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide, DiR) acts as the donor of near-infrared fluorescence (NIRF). In addition, rapamycin (RAPA), which is used as the antiangiogenesis chemotherapeutic drug, can cutdown the tumor vessels and delay tumor growth obviously. After intravenous treatment of RDLPNPs into Hela tumor bearing mice, fluorescent (from DiR) and enhanced photoacoustic (from DLPNPs) signals were found in tumor site over time, which reached to peak at the 6h time point. After irradiating with an NIR laser, a good anti-tumor effect was observed owing to the enhanced photothermal and antiangiogenic effect of RDLPNPs. These results show that the multifunctional nanoparticle can be used as a promising imaging-guided photothermal drug delivery nanoplatform for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Neuroprotective effects of Lepidium meyenii (Maca).

    Science.gov (United States)

    Pino-Figueroa, Alejandro; Nguyen, Diane; Maher, Timothy J

    2010-06-01

    The neuroprotective activity of the plant Lepidium meyenii (Maca) was studied in two experimental models: in vitro and in vivo. Crayfish neurons were pretreated with vehicle or the pentane extract from Maca, subjected to H(2)O(2), and their viability determined microscopically and chemically. A significant concentration-neuroprotective effect relationship was demonstrated. The pentane extract was then administered intravenously to rats prior to and following middle cerebral artery occlusion. While infarct volumes were decreased for the lower dose, higher doses increased infarct volumes compared to controls. These results suggest a potential application of Maca as a neuroprotectant.

  16. Conservative treatment modalities in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Bhavna Chawla

    2013-01-01

    Full Text Available Retinoblastoma is the most common primary intraocular malignancy of childhood. A potentially curable cancer, its treatment has improved significantly over the last few decades. The purpose of this article is to review the literature on various conservative treatment modalities available for the treatment of retinoblastoma and their effectiveness, when used alone or in combination. Pubmed, Medline, Embase, and the Cochrane library were searched through 2012 for published peer reviewed data on conservative treatment modalities for retinoblastoma. Various studies show that while enucleation remains the standard of care for advanced intraocular tumors, conservative modalities that can result in globe salvage and preservation of useful vision are being increasingly employed. Such modalities include systemic chemotherapy, focal consolidation with transpupillary thermotherapy, laser photocoagulation and cryotherapy, plaque brachytherapy, and delivery of local chemotherapy using subconjunctival, sub-tenon, or intra-arterial routes. When used alone or in combination, these treatment modalities can help in avoidance of external beam radiotherapy or enucleation, thus reducing the potential for long-term side effects, while salvaging useful vision. Radioactive plaque brachytherapy has an established role in selected patients with intraocular retinoblastoma. Local injections of chemotherapeutic agents via the sub-tenon or sub-conjunctival route have been used with varying degrees of success, usually as an adjunct to systemic chemotherapy. Intra-arterial ophthalmic artery delivery of melphalan has shown promising results. It is important to recognize that today, several treatment options are available that can obviate the need for enucleation, and cure the cancer with preservation of functional vision. A thorough knowledge and understanding of these conservative treatment modalities is essential for appropriate management.

  17. Conservative treatment modalities in retinoblastoma

    Science.gov (United States)

    Chawla, Bhavna; Jain, Amit; Azad, Rajvardhan

    2013-01-01

    Retinoblastoma is the most common primary intraocular malignancy of childhood. A potentially curable cancer, its treatment has improved significantly over the last few decades. The purpose of this article is to review the literature on various conservative treatment modalities available for the treatment of retinoblastoma and their effectiveness, when used alone or in combination. Pubmed, Medline, Embase, and the Cochrane library were searched through 2012 for published peer reviewed data on conservative treatment modalities for retinoblastoma. Various studies show that while enucleation remains the standard of care for advanced intraocular tumors, conservative modalities that can result in globe salvage and preservation of useful vision are being increasingly employed. Such modalities include systemic chemotherapy, focal consolidation with transpupillary thermotherapy, laser photocoagulation and cryotherapy, plaque brachytherapy, and delivery of local chemotherapy using subconjunctival, sub-tenon, or intra-arterial routes. When used alone or in combination, these treatment modalities can help in avoidance of external beam radiotherapy or enucleation, thus reducing the potential for long-term side effects, while salvaging useful vision. Radioactive plaque brachytherapy has an established role in selected patients with intraocular retinoblastoma. Local injections of chemotherapeutic agents via the sub-tenon or sub-conjunctival route have been used with varying degrees of success, usually as an adjunct to systemic chemotherapy. Intra-arterial ophthalmic artery delivery of melphalan has shown promising results. It is important to recognize that today, several treatment options are available that can obviate the need for enucleation, and cure the cancer with preservation of functional vision. A thorough knowledge and understanding of these conservative treatment modalities is essential for appropriate management. PMID:24104705

  18. High serum levels of vascular endothelial growth factor-A and transforming growth factor-β1 before neoadjuvant chemoradiotherapy predict poor outcomes in patients with esophageal squamous cell carcinoma receiving combined modality therapy.

    Science.gov (United States)

    Cheng, Jason Chia-Hsien; Graber, Madeline S; Hsu, Feng-Ming; Tsai, Chiao-Ling; Castaneda, Leon; Lee, Jang-Ming; Chang, Daniel T; Koong, Albert C

    2014-07-01

    This study was aimed at using proximity ligation assay (PLA) followed by enzyme-linked immunosorbent assay (ELISA) to identify serum biomarkers that predict treatment response and survival for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy. Seventy-nine patients with ESCC receiving CCRT of taxane-based/5-fluorouracil-based chemotherapy and 40 Gy followed by surgery were enrolled. Serum samples were collected before and combined high pre-CCRT VEGF-A and TGF-β1 levels (greater than or equal to the median), independent of pathological response, had significantly worse DFS (11 months vs. median not reached; p = 0.007) and OS (16 vs. 46 months; p = 0.07). Pre-CCRT serum VEGF-A and TGF-β1 levels may be used to predict pathological response and survivals for ESCC patients receiving combined-modality therapy.

  19. Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke.

    Science.gov (United States)

    Karsy, Michael; Brock, Andrea; Guan, Jian; Taussky, Phillip; Kalani, M Yashar S; Park, Min S

    2017-04-01

    Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade. Results of historical research trials involving N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonists, clomethiazole, antioxidants, citicoline, nitric oxide, and immune regulators have laid the groundwork for current progress. In addition, more recent studies involving therapeutic hypothermia, magnesium, albumin, glyburide, uric acid, and a variety of other treatments have provided more options. The use of neuroprotective agents in combination or with existing thrombolytic treatments may be one of many exciting areas of further development. Although past trials of neuroprotective agents in ischemic stroke have been limited, significant insights into mechanisms of stroke, animal models, and trial design have incrementally improved approaches for future therapies.

  20. Radiotherapy and cis-diammine dichloroplatinum (II) as a combined treatment modality for inoperable non-small cell lung cancer: a dose finding study

    NARCIS (Netherlands)

    Schaake-Koning, C.; Bartelink, H.; Adema, B. H.; Schuster-Uitterhoeve, L.; van Zandwijk, N.

    1986-01-01

    A dose finding study was carried out to establish the dose of cis-diammine dichloroplatinum (II), cDDP, that can be combined with high dose radiotherapy routinely in patients with inoperable non-small cell lung cancer. The patients were irradiated over a period of 2 weeks, 5 fractions a week,

  1. A combined salt-hard templating approach for synthesis of multi-modal porous carbons used for probing the simultaneous effects of porosity and electrode engineering on EDLC performance

    KAUST Repository

    Bhandari, Nidhi

    2015-06-01

    A new approach, based on a combination of salt and hard templating for producing multi-modal porous carbons is demonstrated. The hard template, silica nanoparticles, generate mesopores (∼22 nm), and in some cases borderline-macropores (∼64 nm), resulting in high pore volume (∼3.9 cm3/g) while the salt template, zinc chloride, generates borderline-mesopores (∼2 nm), thus imparting high surface area (∼2100 m2/g). The versatility of the proposed synthesis technique is demonstrated using: (i) dual salt templates with hard template resulting in magnetic, nanostructured-clay embedded (∼27% clay content), high surface area (∼1527 m2/g) bimodal carbons (∼2 and 70 nm pores), (ii) multiple hard templates with salt template resulting in tri-modal carbons (∼2, 12 and 28 nm pores), (iii) low temperature (450 °C) synthesis of bimodal carbons afforded by the presence of hygroscopic salt template, (iv) easy coupling with physical activation approaches. A selected set of thus synthesized carbons were used to evaluate, for the first time, the simultaneous effects of carbon porosity and pressure applied during electrode fabrication on EDLC performance. Electrode pressing was found to be more favorable for carbons containing hard-templated mesopores (∼87% capacitance retention at current density of 40 A/g) as compared to those without (∼54% capacitance retention). © 2015 Elsevier Ltd. All rights reserved.

  2. Use of Adjuvant Chemotherapy, Radiation Therapy, or Combined Modality Therapy and the Impact on Survival for Uterine Carcinosarcoma Limited to the Pelvis.

    Science.gov (United States)

    Wong, Andrew T; Lee, Yi-Chun; Schwartz, David; Lee, Anna; Shao, Meng; Han, Peter; Choi, Kwang; Schreiber, David

    2017-07-01

    Clinical outcomes for patients with uterine carcinosarcoma are poor after surgical management alone. Adjuvant therapies including chemotherapy (CT) and/or radiation therapy (RT) have been previously investigated, but the optimal management of this disease remains controversial. The purposes of this study were to analyze the patterns of use of adjuvant CT and RT and to assess the impact on survival of each of these treatment regimens using the National Cancer Data Base. The National Cancer Data Base was queried for patients given a diagnosis of uterine carcinosarcoma confined to the pelvis who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011. Patients were excluded if they survived less than 4 months after diagnosis. Data regarding CT and RT use were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to evaluate the effect of covariates on OS. A total of 4906 patients were included in this study. Median age was 67 years (interquartile range, 60-75 years). Median follow-up was 28.9 months (interquartile range, 15.4-52.9 months). There were 1777 patients (36.2%) who received no adjuvant treatment, 971 (19.8%) who received CT alone, 1060 (21.6%) who received RT alone, and 1098 (22.4%) who received both RT and CT. The 5-year OS for patients receiving no adjuvant therapy, adjuvant RT alone, adjuvant CT alone, and combined CT and RT were 44.9%, 47.1%, 47.5%, and 62.9%, respectively. On pairwise analysis, combined CT and RT was associated with improved survival compared with all other subgroups (P combined CT and RT (hazard ratio, 0.50; 95% confidence interval, 0.44-0.57; P Combination therapy with CT and RT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone.

  3. Advances in Modal Logic

    DEFF Research Database (Denmark)

    Modal logic is a subject with ancient roots in the western logical tradition. Up until the last few generations, it was pursued mainly as a branch of philosophy. But in recent years, the subject has taken new directions with connections to topics in computer science and mathematics. This volume...... is the proceedings of the conference of record in its fi eld, Advances in Modal Logic. Its contributions are state-of-the-art papers. The topics include decidability and complexity results for specifi c modal logics, proof theory of modal logic, logics for reasoning about time and space, provability logic, dynamic...... epistemic logic, and the logic of evidence....

  4. Combined modality doxorubicin-based chemotherapy and chitosan-mediated p53 gene therapy using double-walled microspheres for treatment of human hepatocellular carcinoma.

    Science.gov (United States)

    Xu, Qingxing; Leong, Jiayu; Chua, Qi Yi; Chi, Yu Tse; Chow, Pierce Kah-Hoe; Pack, Daniel W; Wang, Chi-Hwa

    2013-07-01

    The therapeutic efficiency of combined chemotherapy and gene therapy on human hepatocellular carcinoma HepG2 cells was investigated using double-walled microspheres that consisted of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(L-lactic acid) (PLLA) shell layer and fabricated via the precision particle fabrication (PPF) technique. Here, double-walled microspheres were used to deliver doxorubicin (Dox) and/or chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53), loaded in the core and shell phases, respectively. Preliminary studies on chi-DNA nanoparticles were performed to optimize gene transfer to HepG2 cells. The transfection efficiency of chi-DNA nanoparticles was optimal at an N/P ratio of 7. In comparison to the 25-kDa branched polyethylenimine (PEI), chitosan showed no inherent toxicity towards the cells. Next, the therapeutic efficiencies of Dox and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins. Overall, the combined Dox and chi-p53 treatment exhibited enhanced cytotoxicity as compared to either Dox or chi-p53 treatments alone. Moreover, the antiproliferative effect was more substantial when cells were treated with microspheres than those treated with free drugs. High p53 expression was maintained during a five-day period, and was largely due to the controlled and sustained release of the microspheres. Moreover, increased activation of caspase 3 was observed, and was likely to have been facilitated by high levels of p53 expression. Overall, double-walled microspheres present a promising dual anticancer delivery system for combined chemotherapy and gene therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    Directory of Open Access Journals (Sweden)

    Zanatta Daniela B

    2010-06-01

    Full Text Available Abstract Background Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods B16 (mouse melanoma and C6 (rat glioma cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet

  6. Combined modality treatment of the rhabdomyosarcoma R1H of the rat: tumor and normal tissue response after cisplatin and conventional or accelerated irradiation treatment

    International Nuclear Information System (INIS)

    Wuerschmidt, Florian; Beck-Bornholdt, Hans-Peter

    1995-01-01

    Purpose: To test the importance of the sequence of cisplatin and irradiation, either conventional or accelerated fractionated. Methods and Materials: 30 fractions of 2 Gy were given in 6 or 3 weeks preceded or followed by (time interval between cisplatin and radiotherapy: 3 days) a single IP dose of 5 mg/kg cisplatin in the rhabdomyosarcoma R1H of the rat. Survival curves were generated, and comparisons were made by the log-rank test. Results: After 60 Gy in 6 weeks, no local tumor controls were observed. If cisplatin was injected 3 days before start of 60 Gy/6 weeks, 11 ± 10% (mean ± SE) of the tumors were controlled. Cisplatin after radiotherapy resulted in 50 ± 14% local controls. The difference was significant (p 0.01) for cisplatin after radiotherapy in comparison to radiotherapy alone where no local controls were observed. After accelerated fractionation, 57 ± 19% of the animals were cured with or without cisplatin before radiotherapy. If the drug was injected after end of 60 Gy/3 weeks, 86 ± 13% survived recurrence free. The difference to accelerated radiotherapy alone was not significant. Accelerated radiotherapy produced significantly higher control rates than conventional radiotherapy (p < 0.001). Conclusions: Accelerated radiotherapy resulted in higher local tumor control rates as compared to conventional fractionated irradiation. Cisplatin combined with radiotherapy showed significantly better results if given after but not before irradiation, either conventional or accelerated fractionated

  7. Long-term results from a randomized phase II trial of neoadjuvant combined-modality therapy for locally advanced rectal cancer

    Directory of Open Access Journals (Sweden)

    Oblak Irena

    2010-09-01

    Full Text Available Abstract Background This study evaluated the effectiveness and safety of preoperative chemoradiotherapy with capecitabine in patients with locally advanced resectable rectal cancer. This report summarizes the results of the phase II study together with long-term (5-year follow-up. Methods Between June 2004 and January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of the rectum entered the study. Radiation dose was 45 Gy delivered as 25 fractions of 1.8 Gy. Concurrent chemotherapy with oral capecitabine 825 mg/m2 twice daily was administered during radiotherapy and at weekends. Surgery was scheduled 6 weeks after the completion of the chemoradiotherapy. Patients received four cycles of postoperative chemotherapy comprising either capecitabine 1250 mg/m2 bid days 1-14 every 3 weeks or bolus i.v. 5-fluorouracil 425 mg/m2/day and leucovorin 20 mg/m2/day days 1-5 every 4 weeks (choice was at the oncologist's discretion. Study endpoints included complete pathological remission, proportion of R0 resections and sphincter-sparing procedures, toxicity, survival parameters and long-term (5-year rectal and urogenital morbidity assessment. Results One patient died after receiving 27 Gy because of a pulmonary embolism. Fifty-six patients completed radiochemotherapy and had surgery. Median follow-up time was 62 months. No patients were lost to follow-up. R0 resection was achieved in 55 patients. A complete pathological response was observed in 5 patients (9.1%; T-, N- and overall downstaging rates were 40%, 52.9% and 49.1%, respectively. The 5-year overall survival rate, recurrence-free survival, and local control was 61.4% (95% CI: 48.9-73.9%, 52.4% (95% CI: 39.3-65.5%, and 87.4% (95% CI: 75.0-99.8%, respectively. In 5 patients local relapse has occurred; dissemination was observed in 19 patients and secondary malignancies have occurred in 2 patients. The most frequent side-effect of the preoperative combined therapy was dermatitis

  8. Extending Modal Transition Systems with Structured Labels

    DEFF Research Database (Denmark)

    Bauer, Sebastian S.; Juhl, Line; Larsen, Kim Guldstrand

    2012-01-01

    We introduce a novel formalism of label-structured modal transition systems that combines the classical may/must modalities on transitions with structured labels that represent quantitative aspects of the model. On the one hand, the specification formalism is general enough to include models like...... weighted modal transition systems and allows the system developers to employ more complex label refinement than in the previously studied theories. On the other hand, the formalism maintains the desirable properties required by any specification theory supporting compositional reasoning. In particular, we...

  9. 111In-cetuximab-F(ab')2 SPECT and 18F-FDG PET for prediction and response monitoring of combined-modality treatment of human head and neck carcinomas in a mouse model.

    Science.gov (United States)

    van Dijk, Laura K; Boerman, Otto C; Franssen, Gerben M; Kaanders, Johannes H A M; Bussink, Johan

    2015-02-01

    Treatment of head and neck squamous cell carcinomas with radiotherapy and the epidermal growth factor receptor (EGFR) inhibitor cetuximab shows an improved response in a subgroup of patients. The aim of this study was to noninvasively monitor treatment response by visualizing systemically accessible EGFR with (111)In-cetuximab-F(ab')2 while simultaneously evaluating tumor metabolism with (18)F-FDG PET during combined-modality treatment. Eighty mice with patient-derived head and neck squamous cell carcinomas xenografts, SCCNij202 or SCCNij185, were imaged with SPECT/CT using (111)In-cetuximab-F(ab')2 (5 μg, 28 ± 6.1 MBq, 24 h after injection), followed by PET imaging with (18)F-FDG (9.4 ± 2.9 MBq, 1 h after injection). Scans were acquired on mice 10 d before treatment with either single-dose irradiation (10 Gy), cetuximab alone, or cetuximab-plus-irradiation combined or on untreated control mice. Scans were repeated 18 d after treatment. Tumor growth was monitored up to 120 d after treatment. EGFR expression was evaluated immunohistochemically. SCCNij202 responded to combined treatment (P combined treatment (P therapy. A positive response to treatment significantly correlated with a reduced tracer uptake in the tumor in the second SPECT scan, compared with the first scan (P therapy was characterized by a significantly increased (111)In-cetuximab-F(ab')2 tumor uptake; tumor-to-liver ratio was 2.2 ± 0.6 to 3.5 ± 1.2, P therapies. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  10. Epigenetics and Therapeutic Targets Mediating Neuroprotection

    Science.gov (United States)

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

    The rapidly evolving science of epigenetics is transforming our understanding of the nervous system in health and disease and holds great promise for the development of novel diagnostic and therapeutic approaches targeting neurological diseases. Increasing evidence suggests that epigenetic factors and mechanisms serve as important mediators of the pathogenic processes that lead to irrevocable neural injury and of countervailing homeostatic and regenerative responses. Epigenetics is, therefore, of considerable translational significance to the field of neuroprotection. In this brief review, we provide an overview of epigenetic mechanisms and highlight the emerging roles played by epigenetic processes in neural cell dysfunction and death and in resultant neuroprotective responses. PMID:26236020

  11. Metallothionein-I+II in neuroprotection

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Jensen, Rikke; Pedersen, Dan S

    2009-01-01

    Metallothionein (MT)-I+II synthesis is induced in the central nervous system (CNS) in response to practically any pathogen or disorder, where it is increased mainly in reactive glia. MT-I+II are involved in host defence reactions and neuroprotection during neuropathological conditions, in which MT...... and scavenging of reactive oxygen species (ROS) leading to cellular redox control. By regulating metal ions, MT-I+II can control metal-containing transcription factors, zinc-finger proteins and p53. However, the neuroprotective functions of MT-I+II also involve an extracellular component. MT-I+II protects...

  12. Wine Polyphenols: Potential Agents in Neuroprotection

    Science.gov (United States)

    Basli, Abdelkader; Soulet, Stéphanie; Chaher, Nassima; Mérillon, Jean-Michel; Chibane, Mohamed; Monti, Jean-Pierre; Richard, Tristan

    2012-01-01

    There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson's or Alzheimer's diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols. PMID:22829964

  13. Normal modal preferential consequence

    CSIR Research Space (South Africa)

    Britz, K

    2012-12-01

    Full Text Available beyond the basic (propositional) KLM postulates, thereby making use of the additional expressivity provided by modal logic. In particular, we show that the additional constraints we impose on the preferential semantics ensure that the rule...

  14. Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities

    Energy Technology Data Exchange (ETDEWEB)

    Kolk, A. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Oral and Maxillofacial Surgery, Munich (Germany); Klinikum rechts der Isar, Technische Universitaet Muenchen, Klinik und Poliklinik fuer Mund-Kiefer und Gesichtschirurgie, Muenchen (Germany); Schuster, T. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Institute of Medical Statistics and Epidemiology, Munich (Germany); Chlebowski, A.; Kesting, M.; Bissinger, O.; Weitz, J. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Oral and Maxillofacial Surgery, Munich (Germany); Lange, P. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Diagnostic Radiology, Munich (Germany); Scheidhauer, K.; Schwaiger, M.; Dinges, J. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany)

    2014-07-15

    Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with {sup 99m}Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent {sup 99m}Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data

  15. Nonparametric modal regression

    OpenAIRE

    Chen, Yen-Chi; Genovese, Christopher R.; Tibshirani, Ryan J.; Wasserman, Larry

    2016-01-01

    Modal regression estimates the local modes of the distribution of $Y$ given $X=x$, instead of the mean, as in the usual regression sense, and can hence reveal important structure missed by usual regression methods. We study a simple nonparametric method for modal regression, based on a kernel density estimate (KDE) of the joint distribution of $Y$ and $X$. We derive asymptotic error bounds for this method, and propose techniques for constructing confidence sets and prediction sets. The latter...

  16. Modality effects in implicit artificial grammar learning: An EEG study.

    Science.gov (United States)

    Silva, Susana; Folia, Vasiliki; Inácio, Filomena; Castro, São Luís; Petersson, Karl Magnus

    2018-05-15

    Recently, it has been proposed that sequence learning engages a combination of modality-specific operating networks and modality-independent computational principles. In the present study, we compared the behavioural and EEG outcomes of implicit artificial grammar learning in the visual vs. auditory modality. We controlled for the influence of surface characteristics of sequences (Associative Chunk Strength), thus focusing on the strictly structural aspects of sequence learning, and we adapted the paradigms to compensate for known frailties of the visual modality compared to audition (temporal presentation, fast presentation rate). The behavioural outcomes were similar across modalities. Favouring the idea of modality-specificity, ERPs in response to grammar violations differed in topography and latency (earlier and more anterior component in the visual modality), and ERPs in response to surface features emerged only in the auditory modality. In favour of modality-independence, we observed three common functional properties in the late ERPs of the two grammars: both were free of interactions between structural and surface influences, both were more extended in a grammaticality classification test than in a preference classification test, and both correlated positively and strongly with theta event-related-synchronization during baseline testing. Our findings support the idea of modality-specificity combined with modality-independence, and suggest that memory for visual vs. auditory sequences may largely contribute to cross-modal differences. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Combined Modality Therapy for Rectal Cancer.

    Science.gov (United States)

    Patel, Sagar A; Ryan, David P; Hong, Theodore S

    2016-01-01

    The primary therapy for any potentially curative rectal cancer is surgery. For locally advanced tumors (i.e., T3-4 and/or node positive), the very high rate of local and distant recurrences has necessitated a standard adjuvant regimen of preoperative chemoradiation and postoperative chemotherapy. Several controversies regarding this approach remain, including the technique and fractionation scheme of radiation therapy prior to surgery, the choice of concomitant chemotherapy, and whether all patients require postoperative systemic therapy. Furthermore, in an era of improving staging imaging and surgical techniques, an opportunity for de-escalation of therapy to improve patient morbidity and quality of life may arise. At the same time, advances in radiation and systemic therapy may help facilitate less invasive, sphincter-preserving surgery. This review addresses these questions and others that remain areas of active clinical investigation.

  18. Neuroprotective effect of paeonol against isoflurane- induced ...

    African Journals Online (AJOL)

    Purpose: To investigate whether paeonol affords neuroprotection against isoflurane-induced neurotoxicity. Methods: Separate ... significant improvement in the general behaviour and working memory of the rats. Conclusion: Paeonol significantly .... any visual impairments and/or swimming difficulties. The pool was covered ...

  19. Ischemic Stroke and Neuroprotection | Onwuekwe | Annals of ...

    African Journals Online (AJOL)

    Stroke is a major cause of morbidity and mortality in both developed and developing countries of the world. Greater understanding of the pathophysiology of neuronal damage in ischemic stroke has generated interest in neuroprotection as a management strategy. This paper aims to review the current concept and place of ...

  20. NAP (davunetide) provides functional and structural neuroprotection.

    Science.gov (United States)

    Gozes, Illana

    2011-01-01

    NAP (davunetide) is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo. In human clinical trials, NAP has been shown to increase memory scores in patients suffering from amnestic mild cognitive impairment, a precursor to Alzheimer's disease and to enhance functional daily behaviors in schizophrenia patients. NAP is derived from activity-dependent neuroprotective protein (ADNP) a molecule that is essential for brain formation, interacting with chromatin associated protein alpha and the chromatin remodeling complex SWI/SNF and regulating >400 genes during embryonic development. Partial loss in ADNP results in cognitive deficits and pathology of the microtubule associated protein tau (tauopathy) that is ameliorated in part by NAP replacement therapy. Recent studies increased the scope of NAP neuroprotection and provided further insights into the NAP mechanisms of action. Thus, it has been hypothesized that the presence of tau on axonal microtubules renders them notably less sensitive to the microtubule-severing protein katanin, and NAP was shown to protect microtubules from katanin disruption in the face of reduced tau expression. Parallel studies showed that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. The interaction of these disparate yet complementary pathways is the subject of future studies toward human brain neuroprotection in the clinical scenario.

  1. Neuroprotective effect of paeonol against isofluraneinduced ...

    African Journals Online (AJOL)

    Purpose: To investigate whether paeonol affords neuroprotection against isoflurane-induced neurotoxicity. Methods: Separate groups of neonatal rat pups were administered paeonol (20, 40 or 80 mg/kg) from post-natal day 3 (P3) to post-natal day 15. On post-natal day 7, the pups were exposed to 6 h of isoflurane (0.75 ...

  2. Proliferative Activity and Neuroprotective Effect of Ligustrazene ...

    African Journals Online (AJOL)

    Proliferative Activity and Neuroprotective Effect of. Ligustrazene Derivative by Irritation of Vascular. Endothelial Growth Factor Expression in Middle Cerebral. Artery Occlusion Rats. Zhang Huazheng1, Wang Penglong2, Ren Liwei1, Wang Xiaobo2, Li Guoliang2,. Wang Mina1, Chu Fuhao2, Gong Yan2, Xu Bing2, Bi Siling1, ...

  3. Toward predicate approaches to modality

    CERN Document Server

    Stern, Johannes

    2016-01-01

    In this volume, the author investigates and argues for, a particular answer to the question: What is the right way to logically analyze modalities from natural language within formal languages? The answer is: by formalizing modal expressions in terms of predicates. But, as in the case of truth, the most intuitive modal principles lead to paradox once the modal notions are conceived as predicates. The book discusses the philosophical interpretation of these modal paradoxes and argues that any satisfactory approach to modality will have to face the paradoxes independently of the grammatical category of the modal notion. By systematizing modal principles with respect to their joint consistency and inconsistency, Stern provides an overview of the options and limitations of the predicate approach to modality that may serve as a useful starting point for future work on predicate approaches to modality. Stern also develops a general strategy for constructing philosophically attractive theories of modal notions conce...

  4. Modal Specifications for Probabilistic Timed Systems

    Directory of Open Access Journals (Sweden)

    Tingting Han

    2013-06-01

    Full Text Available Modal automata are a classic formal model for component-based systems that comes equipped with a rich specification theory supporting abstraction, refinement and compositional reasoning. In recent years, quantitative variants of modal automata were introduced for specifying and reasoning about component-based designs for embedded and mobile systems. These respectively generalize modal specification theories for timed and probabilistic systems. In this paper, we define a modal specification language for combined probabilistic timed systems, called abstract probabilistic timed automata, which generalizes existing formalisms. We introduce appropriate syntactic and semantic refinement notions and discuss consistency of our specification language, also with respect to time-divergence. We identify a subclass of our models for which we define the fundamental operations for abstraction, conjunction and parallel composition, and show several compositionality results.

  5. Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

    Directory of Open Access Journals (Sweden)

    Hiroshi Sameshima

    2013-01-01

    Full Text Available Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

  6. The modal study

    International Nuclear Information System (INIS)

    Cook, J.R.

    1988-01-01

    The term ''Modal Study'' refers to a research program conducted for the Nuclear Regulatory Commission (NRC) on the level of protection provided by NRC-certified packages during the shipment of spent nuclear fuel form U.S. power reactors. The objective of the study was to examine the response of the packages to actual highway and railway accident conditions. The Modal Study results show that NRC-certified spent fuel casks would perform their safety functions under severe, actual accident conditions. The study also explains how NRC's cask design conditions, which are expressed in engineering terms, relate to actual accident conditions, with which the public is more familiar. The Modal Study, along with other transportation studies, physical testing of casks, and the spent fuel shipment safety record confirm the view that casks provide a high level of public safety during spent fuel transport

  7. trans-Resveratrol as A Neuroprotectant

    Directory of Open Access Journals (Sweden)

    Ellen L. Robb

    2010-03-01

    Full Text Available Epidemiological evidence indicates that nutritionally-derived polyphenols such as resveratrol (RES have neuroprotective properties. Administration of RES to culture media protects a wide variety of neuronal cell types from stress-induced death. Dietary supplementation of RES can ameliorate neuronal damage and death resulting from both acute and chronic stresses in rodents. The specific molecular mechanisms by which RES acts at the cellular level remain incompletely understood. However, many experimental data indicate that RES reduces or prevents the occurrence of oxidative damage. Here we discuss possible mechanisms by which RES might exert protection against oxidative damage and cell death. Evidence suggesting that RES’s chemical antioxidant potential is not sufficient explanation for its effects is discussed. Putative biological activities, including interactions with estrogen receptors and sirtuins are critically discussed. We provide a synthesis of how RES’s phytoestrogenic properties might mediate the neuronal stress resistance underlying its observed neuroprotective properties.

  8. Wine Polyphenols: Potential Agents in Neuroprotection

    Directory of Open Access Journals (Sweden)

    Abdelkader Basli

    2012-01-01

    Full Text Available There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson’s or Alzheimer’s diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols.

  9. MODAL MANUSIA DAN PRODUKTIVITAS

    Directory of Open Access Journals (Sweden)

    Erlinda Puspita Sari

    2014-03-01

    Full Text Available Modal manusia dianggap sebagai salah satu faktor penentu produktivitas. Modal manusia merupakan dimensi kualitatif dari sumberdaya manusia, seperti keahlian dan keterampilan, yang akan memengaruhi kemampuan produktif manusia tersebut. Dimensi kualitatif tersebut diperoleh melalui pendidikan, pelatihan dan kesehatan. Penelitian ini bertujuan untuk menganaliss efek dari modal manusia terhadap tingkat produktivitas di provinsi-provinsi di Indonesia. Dalam penelitian ini, tingkat pendidikan diukur dengan beberapa indikator, yaitu; angka melek huruf dan angka partisipasi murni tingkat SD, SMP maupun SMA. Tingkat kesehatan diukur dengan angka kematian bayi. Data yang digunakan adalah data panel dari 25 provinsi di Indonesia selama perioede 1996-2010 yang dianalisis dengan menggunakan Model Panel Data Fixed Effect. Hasil analisis menunjukkan bahwa modal manusia yang diukur dari tingkat pendidikan (APM dan tingkat kesehatan (AKB merupakan faktor yang berpengaruh dan signifikan untuk menjelaskan variasi produktivitas meskipun magnitude-nya lebih kecil dibandingkan dengan modal fisik. Hasil analisis juga menunjukkan bahwa variabel pendidikan memiliki magnitude yang lebih besar dibandingkan dengan variabel kesehatan. Human capital is regarded as one of the determining factors of productivity. Human capital is qualitative dimension of human resource which includes skills and knowledge. These qualitative dimensions are internalized through education, training and health. This study aimed to analyze the effect of human capital on productivity level across provinces in Indonesia. In this study, the level of education was measured by literacy and school enrollment rate (in primary, secondary and high school. The level of health was measured by infant mortality rate. The study employed a panel data of 25 provinces in Indonesia during the period of 1996-2010. Using fixed effect method, the result showed that secondary school enrollment rate and infant mortality

  10. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233.

    Science.gov (United States)

    Mak, Raymond H; Hunt, Daniel; Shipley, William U; Efstathiou, Jason A; Tester, William J; Hagan, Michael P; Kaufman, Donald S; Heney, Niall M; Zietman, Anthony L

    2014-12-01

    Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies. Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903). Overall survival (OS) was estimated using the Kaplan-Meier method, and disease-specific survival (DSS), muscle-invasive and non-muscle-invasive local failure (LF), and distant metastasis (DM) were estimated by the cumulative incidence method. The median age of patients was 66 years (range, 34 to 93 years), and clinical T stage was T2 in 61%, T3 in 35%, and T4a in 4% of patients. Complete response to CMT was documented in 69% of patients. With a median follow-up of 4.3 years among all patients and 7.8 years among survivors (n = 205), the 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and 10-year DSS rates were 71% and 65%, respectively. The 5- and 10-year estimates of muscle-invasive LF, non-muscle-invasive LF, and DM were 13% and 14%, 31% and 36%, and 31% and 35%, respectively. This pooled analysis of multicenter, prospective RTOG bladder-preserving CMT protocols demonstrates long-term DSS comparable to modern immediate cystectomy studies, for patients with similarly staged MIBC. Given the low incidence of late recurrences with long-term follow-up, CMT can be considered as an alternative to radical cystectomy, especially in elderly patients not well suited for surgery. © 2014 by American Society of Clinical Oncology.

  11. A Modal Model to Simulate Typical Structural Dynamic Nonlinearity

    Energy Technology Data Exchange (ETDEWEB)

    Pacini, Benjamin Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mayes, Randall L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Roettgen, Daniel R [Univ. of Wisconsin, Madison, WI (United States)

    2015-10-01

    Some initial investigations have been published which simulate nonlinear response with almost traditional modal models: instead of connecting the modal mass to ground through the traditional spring and damper, a nonlinear Iwan element was added. This assumes that the mode shapes do not change with amplitude and there are no interactions between modal degrees of freedom. This work expands on these previous studies. An impact experiment is performed on a structure which exhibits typical structural dynamic nonlinear response, i.e. weak frequency dependence and strong damping dependence on the amplitude of vibration. Use of low level modal test results in combination with high level impacts are processed using various combinations of modal filtering, the Hilbert Transform and band-pass filtering to develop response data that are then fit with various nonlinear elements to create a nonlinear pseudo-modal model. Simulations of forced response are compared with high level experimental data for various nonlinear element assumptions.

  12. The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Edward C. Lauterbach

    2012-01-01

    Full Text Available Neuroprotective treatments in Parkinson's disease (PD have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R, although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS, reactive nitrogen species (RNS, apoptosis, inflammation, and trophic factors including GDNF and BDNF.

  13. The modality effect and echoic persistence.

    Science.gov (United States)

    Watkins, O C; Watkins, M J

    1980-09-01

    The modality effect refers to the higher level of recall of the last few items of a list when presentation is auditory as opposed to visual. It is usually attributed to echoic memory. The effect may be sharply reduced by an ostensibly irrelevant auditory item appended to the end of the list. Previous research suggests that this "suffix effect" arises only when the suffix item occurs within 2 sec of the last list item. This finding strengthens the widely held assumption that echoic information decays within 2 sec, and has led to the assumption that if echoic information is to be useful in serial recall it must first be encoded into a more durable modality-independent form. Both assumptions conflict with the research reported here. The first two experiments demonstrate substantial suffix effects with suffix delays of 2 and 4 sec, indicating that echoic information lasts at least 4 sec. This finding implies that echoic information may aid recall directly, an implication that was supported in Experiments 3 and 4. In Experiment 3 serial recall was interrupted with a brief distractor task. The modality effect was smaller when this task was auditory than when it was visual, suggesting that echoic information was still available immediately prior to recency recall. In Experiment 4 list presentation was broken by a 4-sec pause; the modalities of the list halves were combined factorially. Interest focused on the recency positions of the first half. A modality effect was found at these positions when the second half was visual but not when it was auditory. This is contrary to the hypothesis that echoic information is encoded before recall, but is consistent with the hypothesis that echoic information is encoded before recall, but is consistent with the alternative hypothesis that echoic information is used directly at recall. The final two experiments concern the modality effect found when a delay is interpolated between list presentation and recall. Experiment 5 showed that

  14. Constructions, pragmatics and modality

    Directory of Open Access Journals (Sweden)

    Antonio Fortin

    2013-05-01

    Full Text Available This paper rejects the commonplace view that the semantics of certain modal deverbal adjectives (MDAs, which have traditionally been assumed to be non-compositional, require complex lexical or syntactic encoding (cf. e.g. Riehemann 1994 and 1998, Booij 2007 and 2010a. Instead, it shows that productive MDA formation is semantically compositional, and that the prima facie idiosyncratic meanings are, in fact, conversational implicatures.

  15. Preferential reasoning for modal logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-11-01

    Full Text Available representation results for both preferential and rational consequence, which paves the way for effective decision procedures for modal preferential reasoning. They then illustrate applications of their constructions to modal logics widely used in AI, notably...

  16. Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

    Science.gov (United States)

    2014-06-02

    Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for traumatic brain injury. Front Neuroendocrinol...Taylor).Marcus K. Taylor a,b,c,⇑, Michael Stone a,c, Heidemarie K. Laurent b, d , Mitchell J. Rauh a,c, Douglas A. Granger b,e aBiobehavioral Sciences...and neurogenesis [20]. Regarding neuroprotection, DHEA(S) is thought to exert pro-survival effects by modulating gamma-ami- nobutyric acid [18

  17. Cerium and yttrium oxide nanoparticles are neuroprotective

    International Nuclear Information System (INIS)

    Schubert, David; Dargusch, Richard; Raitano, Joan; Chan, S.-W.

    2006-01-01

    The responses of cells exposed to nanoparticles have been studied with regard to toxicity, but very little attention has been paid to the possibility that some types of particles can protect cells from various forms of lethal stress. It is shown here that nanoparticles composed of cerium oxide or yttrium oxide protect nerve cells from oxidative stress and that the neuroprotection is independent of particle size. The ceria and yttria nanoparticles act as direct antioxidants to limit the amount of reactive oxygen species required to kill the cells. It follows that this group of nanoparticles could be used to modulate oxidative stress in biological systems

  18. Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni

    2005-01-01

    neuroprotective effect when tested in an oxygen glucose deprivation (OGD) cell culture test. The same compounds were preliminarily assayed using Xenopus oocytes expressing cloned rat NMDA receptors containing the NR1 subunit in combination with either NR2A, NR2B, NR2C, or NR2D subunit. In this assay, all three...

  19. Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with neuroprotective activity.

    Science.gov (United States)

    Garcia, Ignacio; Vior, Natalia M; González-Sabín, Javier; Braña, Alfredo F; Rohr, Jürgen; Moris, Francisco; Méndez, Carmen; Salas, José A

    2013-08-22

    Collismycin A is a member of the 2,2'-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Short-Term Memory in Mathematics-Proficient and Mathematics-Disabled Students as a Function of Input-Modality/Output-Modality Pairings.

    Science.gov (United States)

    Webster, Raymond E.

    1980-01-01

    A significant two-way input modality by output modality interaction suggested that short term memory capacity among the groups differed as a function of the modality used to present the items in combination with the output response required. (Author/CL)

  1. Neuroprotective effect of apocynin nitrone in oxygen glucose ...

    African Journals Online (AJOL)

    Purpose: To investigate the neuroprotective potential of apocynin nitrone (AN-1), a nitrone analogue of apocynin, in rat brain tissue as a novel candidate for ischemic stroke treatment. Methods: In vitro neuroprotection of AN-1 was studied in SH-SY5Y cells treated with oxygen glucose deprivation (OGD). Cell viability was ...

  2. Evaluation of neuroprotective properties of two synthetic prenylated ...

    African Journals Online (AJOL)

    cell death. Determination of MNTD is crucial prior to subsequent neuroprotection assay so that the compound would not pose any neurotoxicity during treatment. This similar approach of MNTD determination first has been used in numerous neuroprotection assays of natural products, such as orientin [9] and edible bird nest ...

  3. Neuroprotective Effects of Lutein in the Retina

    Science.gov (United States)

    Ozawa, Yoko; Sasaki, Mariko; Takahashi, Noriko; Kamoshita, Mamoru; Miyake, Seiji; Tsubota, Kazuo

    2012-01-01

    Although a large variety of pharmaceutical therapies for treating disease have been developed in recent years, there has been little progress in disease prevention. In particular, the protection of neural tissue is essential, because it is hardly regenerated. The use of nutraceuticals for maintaining the health has been supported by several clinical studies, including cross-sectional and interventional studies for age-related macular disease. However, mechanistic evidence for their effects at the molecular level has been very limited. In this review, we focus on lutein, which is a xanthophyll type of carotenoid. Lutein is not synthesized in mammals, and must be obtained from the diet. It is delivered to the retina, and in humans, it is concentrated in the macula. Here, we describe the neuroprotective effects of lutein and their underlying molecular mechanisms in animal models of vision-threatening diseases, such as innate retinal inflammation, diabetic retinopathy, and light-induced retinal degeneration. In lutein-treated mouse ocular disease models, oxidative stress in the retina is reduced, and its downstream pathological signals are inhibited. Furthermore, degradation of the functional proteins, rhodopsin (a visual substance) and synaptophysin (a synaptic vesicle protein also influenced in other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease), the depletion of brain-derived neurotrophic factor (BDNF), and DNA damage are prevented by lutein, which preserves visual function. We discuss the possibility of using lutein, an antioxidant, as a neuroprotective treatment for humans. PMID:22211688

  4. Nutraceutical Antioxidants as Novel Neuroprotective Agents

    Directory of Open Access Journals (Sweden)

    Daniel A. Linseman

    2010-11-01

    Full Text Available A variety of antioxidant compounds derived from natural products (nutraceuticals have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1 flavonoid polyphenols like epigallocatechin 3-gallate (EGCG from green tea and quercetin from apples; (2 non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3 phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4 organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2 transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.

  5. Mitochondrial preconditioning: a potential neuroprotective strategy

    Directory of Open Access Journals (Sweden)

    Sónia C Correia

    2010-08-01

    Full Text Available Mitochondria have long been known as the powerhouse of the cell. However, these organelles are also pivotal players in neuronal cell death. Mitochondrial dysfunction is a prominent feature of chronic brain disorders, including Alzheimer's and Parkinson's diseases, and cerebral ischemic stroke. Data derived from morphologic, biochemical and molecular genetic studies indicate that mitochondria constitute a convergence point for neurodegeneration. Conversely, mitochondria have also been implicated in the neuroprotective signaling processes of preconditioning. Despite the precise molecular mechanisms underlying preconditioning-induced brain tolerance are still unclear, mitochondrial reactive oxygen species generation and mitochondrial ATP-sensitive potassium channels activation have been shown to be involved in the preconditioning phenomenon. This review intends to discuss how mitochondrial malfunction contributes to the onset and progression of cerebral ischemic stroke and Alzheimer’s and Parkinson’s diseases, two major neurodegenerative disorders. The role of mitochondrial mechanisms involved in the preconditioning-mediated neuroprotective events will be also discussed. Mitochondrial targeted preconditioning may represent a promising therapeutic weapon to fight neurodegeneration.

  6. Metaphysical Modality, Modality of Predicate and the Theory of

    Directory of Open Access Journals (Sweden)

    l nabavi

    2010-05-01

    This paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  7. Anesthetic Preconditioning as Endogenous Neuroprotection in Glaucoma

    Directory of Open Access Journals (Sweden)

    Tsung-Han Chou

    2018-01-01

    Full Text Available Blindness in glaucoma is the result of death of Retinal Ganglion Cells (RGCs and their axons. RGC death is generally preceded by a stage of reversible dysfunction and structural remodeling. Current treatments aimed at reducing intraocular pressure (IOP are ineffective or incompletely effective in management of the disease. IOP-independent neuroprotection or neuroprotection as adjuvant to IOP lowering in glaucoma remains a challenge as effective agents without side effects have not been identified yet. We show in DBA/2J mice with spontaneous IOP elevation and glaucoma that the lifespan of functional RGCs can be extended by preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age that temporary blocks RGC axonal transport. The contralateral, PBS-injected eye served as control. Lidocaine-induced impairment of axonal transport to superior colliculi was assessed by intravitreal injection of cholera toxin B. Long-term (nine months effect of lidocaine were assessed on RGC electrical responsiveness (PERG, IOP, expression of relevant protein (BDNF, TrkB, PSD95, GFAP, Synaptophysin, and GAPDH and RGC density. While lidocaine treatment did not alter the age-related increase of IOP, TrkB expression was elevated, GFAP expression was decreased, RGC survival was improved by 35%, and PERG function was preserved. Results suggest that the lifespan of functional RGCs in mouse glaucoma can be extended by preconditioning RGCs in early stages of the disease using a minimally invasive treatment with retrobulbar lidocaine, a common ophthalmologic procedure. Lidocaine is inexpensive, safe and is approved by Food and Drug Administration (FDA to be administered intravenously.

  8. NGF steers microglia toward a neuroprotective phenotype.

    Science.gov (United States)

    Rizzi, Caterina; Tiberi, Alexia; Giustizieri, Michela; Marrone, Maria Cristina; Gobbo, Francesco; Carucci, Nicola Maria; Meli, Giovanni; Arisi, Ivan; D'Onofrio, Mara; Marinelli, Silvia; Capsoni, Simona; Cattaneo, Antonino

    2018-02-23

    Microglia are the sentinels of the brain but a clear understanding of the factors that modulate their activation in physiological and pathological conditions is still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on microglia by steering them toward a neuroprotective and anti-inflammatory phenotype. We show that microglial cells express functional NGF receptors in vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia, NGF treatment leads to a modulation of motility, phagocytosis and degradation pathways. At the functional level, NGF induces an increase in membrane dynamics and macropinocytosis and, in vivo, it activates an outward rectifying current that appears to modulate glutamatergic neurotransmission in nearby neurons. Since microglia are supposed to be a major player in Aβ peptide clearance in the brain, we tested the effects of NGF on its phagocytosis. NGF was shown to promote TrkA-mediated engulfment of Aβ by microglia, and to enhance its degradation. Additionally, the proinflammatory activation induced by Aβ treatment is counteracted by the concomitant administration of NGF. Moreover, by acting specifically on microglia, NGF protects neurons from the Aβ-induced loss of dendritic spines and inhibition of long term potentiation. Finally, in an ex-vivo setup of acute brain slices, we observed a similar increase in Aβ engulfment by microglial cells under the influence of NGF. Our work substantiates a role for NGF in the regulation of microglial homeostatic activities and points toward this neurotrophin as a neuroprotective agent in Aβ accumulation pathologies, via its anti-inflammatory activity on microglia. © 2018 The Authors GLIA Published by Wiley Periodicals, Inc.

  9. Neuroprotection for treatment of glaucoma in adults.

    Science.gov (United States)

    Sena, Dayse F; Lindsley, Kristina

    2017-01-25

    Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 August 2016. We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow-up time was four years. Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we

  10. Mimicry for all modalities.

    Science.gov (United States)

    Dalziell, Anastasia H; Welbergen, Justin A

    2016-06-01

    Mimicry is a canonical example of adaptive signal design. In principle, what constitutes mimicry is independent of the taxonomic identity of the mimic, the ecological context in which it operates, and the sensory modality through which it is expressed. However, in practice the study of mimicry is inconsistent across research fields, with theoretical and empirical advances often failing to cross taxonomic and sensory divides. We propose a novel conceptual framework whereby mimicry evolves if a receiver perceives the similarity between a mimic and a model and as a result confers a selective benefit onto the mimic. Here, misidentification and/or deception are no longer formal requirements, and mimicry can evolve irrespective of the underlying proximate mechanisms. The centrality of receiver perception in this framework enables us to formally distinguish mimicry from perceptual exploitation and integrate mimicry and multicomponent signalling theory for the first time. In addition, it resolves inconsistencies in our understanding of the role of learning in mimicry evolution, and shows that imperfect mimicry is expected to be the norm. Mimicry remains a key model for understanding signal evolution and cognition, and we recommend the adoption of a unified approach to stimulate future interdisciplinary developments in this fascinating area of research. © 2016 John Wiley & Sons Ltd/CNRS.

  11. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well as re...

  12. Modal Logics for Cryptographic Processes

    DEFF Research Database (Denmark)

    Frendrup, U.; Huttel, Hans; Jensen, N. J.

    2002-01-01

    We present three modal logics for the spi-calculus and show that they capture strong versions of the environment sensitive bisimulation introduced by Boreale et al. Our logics differ from conventional modal logics for process calculi in that they allow us to describe the knowledge of an attacker ...

  13. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

    Science.gov (United States)

    Jayaraman, Anusha; Pike, Christian J

    2014-03-25

    Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Neuroprotection against oxidative stress by serum from heat acclimated rats.

    Science.gov (United States)

    Beit-Yannai, E; Trembovler, V; Horowitz, M; Lazarovici, P; Kohen, R; Shohami, E

    1998-09-25

    Exposure of PC12 cells, to 1% serum derived from normothermic (CON) rats resulted in 79% cell death. Sister cultures treated with 1% serum derived from heat acclimated (ACC) rats, were neuroprotected and expressed a significant reduction in cell death. In PC12 cells exposed to a free radical generator causing an oxidative stress, 90% cell death was measured in CON serum treated cultures, while ACC serum treated cultures were neuroprotected. Xanthine oxidase activity and uric acid (UA) levels were lower in ACC serum compared to CON. Addition of UA to both sera abolished the difference in cell viability, and toxicity of ACC serum reached that of CON. These findings suggest a causal relationship between the lower levels of UA in ACC and the neuroprotective effect observed. The present study proposes heat acclimation as an experimental and/or clinical tool for the achievement of neuroprotection.

  15. Potential of neuroprotective antioxidant-based therapeutics from ...

    African Journals Online (AJOL)

    derived antioxidants for the control of neurodegenerative disorders. Antioxidants may have neuroprotective (preventing apoptosis) and neuroregenerative roles, by reducing or reversing cellular damage and by slowing progression of neuronal cell ...

  16. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

    OpenAIRE

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-01

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on m...

  17. Neuroprotection by resveratrol in diabetic neuropathy: concepts & mechanisms.

    Science.gov (United States)

    Kumar, A; Negi, G; Sharma, S S

    2013-01-01

    Resveratrol is a naturally occurring phytoalexin found in many plants, nuts and fruits and is abundant in grapes and red wine. Resveratrol possesses a wide range of biological activities which include antioxidant, anti-inflammatory, chemoprotective, chemopreventive etc. Resveratrol has been investigated extensively in diabetes and its complications which suggest its anti-diabetic activity and protective effect against various diabetic complications. Neurons are extremely susceptible to oxidant-induced damage which may be due to their high rate of oxygen consumption and low levels of antioxidant defence enzymes. Traditionally, it was thought that the protective actions of resveratrol in diabetic neuropathy are due to its intrinsic radical scavenger properties. However, recently many other associated or separate mechanisms like upregulation of Nrf2, SIRT1 and inhibition of NF-κB, AP-1 have been proposed for its beneficial effect against nerve dysfunction. This present review discusses the neuroprotective effects of resveratrol that have been observed in experimental diabetic neuropathy and possible mechanistic explanations, as these effects may provide directions for the development of newer therapies. Futuristic therapies can be based on either resveratrol or its analogs with better bioavailability, or combining the resveratrol with existing therapies.

  18. Operational Modal Analysis of the Cablestayed Footbridge

    Science.gov (United States)

    Kortiš, Ján; Daniel, Ľuboš; Farbák, Matúš; Maliar, Lukáš; Škarupa, Milan

    2017-12-01

    Modern architecture leads to design subtle bridge structures that are more sensitive to increased dynamic loading than the massive ones. This phenomenon can be especially observed on lightweight steel structures such as suspended footbridges. As a result, it is necessary to know precisely its dynamic characteristics, such as natural frequencies, natural shapes and damping of construction. This information can be used for further analysis such as damage detection, system identification, health monitoring, etc. or also for the design of new types of construction. For this purpose, classical modal analysis using trigger load or harmonic vibration exciter in combination with acceleration sensors is used in practice. However, there are many situations where it is not possible to stop the traffic or operation of the bridge. The article presents an experimental measurement of the dynamic parameters of the structure at the operating load using the operational modal analysis.

  19. Mobile Education: Towards Affective Bi-modal Interaction for Adaptivity

    Directory of Open Access Journals (Sweden)

    Efthymios Alepis

    2009-04-01

    Full Text Available One important field where mobile technology can make significant contributions is education. However one criticism in mobile education is that students receive impersonal teaching. Affective computing may give a solution to this problem. In this paper we describe an affective bi-modal educational system for mobile devices. In our research we describe a novel approach of combining information from two modalities namely the keyboard and the microphone through a multi-criteria decision making theory.

  20. Many-dimensional modal logics theory and applications

    CERN Document Server

    Gabbay, D M; Wolter, F; Zakharyaschev, M

    2003-01-01

    Modal logics, originally conceived in philosophy, have recently found many applications in computer science, artificial intelligence, the foundations of mathematics, linguistics and other disciplines. Celebrated for their good computational behaviour, modal logics are used as effective formalisms for talking about time, space, knowledge, beliefs, actions, obligations, provability, etc. However, the nice computational properties can drastically change if we combine some of these formalisms into a many-dimensional system, say, to reason about knowledge bases developing in time or moving objects.

  1. Endocannabinoid signaling in neurotoxicity and neuroprotection.

    Science.gov (United States)

    Pope, C; Mechoulam, R; Parsons, L

    2010-09-01

    The cannabis plant and products produced from it, such as marijuana and hashish, have been used for centuries for their psychoactive properties. The mechanism for how Delta(9)-tetrahydrocannabinol (THC), the active constituent of cannabis, elicits these neurological effects remained elusive until relatively recently, when specific G-protein coupled receptors were discovered that appeared to mediate cellular actions of THC. Shortly after discovery of these specific receptors, endogenous ligands (endocannabinoids) were identified. Since that time, an extensive number of papers have been published on the endocannabinoid signaling system, a widespread neuromodulatory mechanism that influences neurotransmission throughout the nervous system. This paper summarizes presentations given at the 12th International Neurotoxicology Association meeting that described the potential role of endocannabinoids in the expression of neurotoxicity. Dr. Raphael Mechoulam first gave an overview of the discovery of exogenous and endogenous cannabinoids and their potential for neuroprotection in a variety of conditions. Dr. Larry Parsons then described studies suggesting that endocannabinoid signaling may play a selective role in drug reinforcement. Dr. Carey Pope presented information on the role that endocannabinoid signaling may have in the expression of cholinergic toxicity following anticholinesterase exposures. Together, these presentations highlighted the diverse types of neurological insults that may be modulated by endocannabinoids and drugs/toxicants which might influence endocannabinoid signaling pathways. Copyright © 2009 Elsevier Inc. All rights reserved.

  2. Neuroprotection and visual function after optic neuritis.

    Science.gov (United States)

    Petzold, Axel

    2017-02-01

    This article discusses the advantages and pitfalls of testing neuroprotective treatment strategies in patients suffering from optic neuritis. Spectral domain optical coherence tomography now permits for automated segmentation of individual retinal layers. The peripapillary retinal nerve fibre layer (pRNFL) has been used in 13 of the 15 trials reviewed. Twelve trials also made use of electrophysiology. Overestimation of good visual recovery in the past has recently been recognized. Assessment of low contrast visual acuity and colour vision are now mainstream. The availability of highly accurate and robust trial outcome measures has facilitated research on this topic. A single long-term structural outcome measurement of the pRNFL is sufficient. For shorter term, assessments of the ganglion cell/inner plexiform layer and axonal birefringence are promising. Longitudinal blood levels of neurofilament proteins permit to recognize axonal loss at presentation and monitor changes longitudinally. Inner nuclear layer volume changes relate to inflammatory disease activity.Pitfalls are related to the timing of events. Hyperacute recruitment is needed for future trials. The onset of demyelination is not known, which complicates timing of electrophysiological recordings. Optic disc oedema precludes the use of the pRNFL from the affected eye as a baseline variable. The concomitant use of corticosteroids complicates interpretation of trial data.

  3. A Causal Theory of Modality

    Directory of Open Access Journals (Sweden)

    José Tomás Alvarado

    2009-08-01

    Full Text Available This work presents a causal conception of metaphysical modality in which a state of affairs is metaphysically possible if and only if it can be caused (in the past, the present or the future by current entities. The conception is contrasted with what is called the “combinatorial” conception of modality, in which everything can co-exist with anything else. This work explains how the notion of ‘causality’ should be construed in the causal theory, what difference exists between modalities thus defined from nomological modality, how accessibility relations between possible worlds should be interpreted, and what is the relation between the causal conception and the necessity of origin.

  4. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials

    NARCIS (Netherlands)

    Noordijk, Evert M.; Carde, Patrice; Dupouy, Noëlle; Hagenbeek, Anton; Krol, Augustinus D. G.; Kluin-Nelemans, Johanna C.; Tirelli, Umberto; Monconduit, Mathieu; Thomas, José; Eghbali, Houchingue; Aleman, Berthe M. P.; Bosq, Jacques; Vovk, Marjeta; Verschueren, Tom A. M.; Pény, Anne-Marie; Girinsky, Théodore; Raemaekers, John M. M.; Henry-Amar, Michel

    2006-01-01

    PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and

  5. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma : Long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials

    NARCIS (Netherlands)

    Noordijk, Evert M.; Carde, Patrice; Dupouy, Noelle; Hagenbeek, Anton; Krol, Augustinus D. G.; Kluin-Nelemans, Johanna C.; Tirelli, Umberto; Monconduit, Mathieu; Thomas, Jose; Eghbali, Houchingue; Aleman, Berthe M. P.; Bosq, Jacques; Vovk, Marjeta; Verschueren, Tom A. M.; Peny, Anne-Marie; Girinsky, Theodore; Raemaekers, John M. M.; Henry-Amar, Michel

    2006-01-01

    Purpose In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and

  6. Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions.

    Science.gov (United States)

    Pifarré, Paula; Gutierrez-Mecinas, María; Prado, Judith; Usero, Lorena; Roura-Mir, Carme; Giralt, Mercedes; Hidalgo, Juan; García, Agustina

    2014-01-01

    In addition to detrimental inflammation, widespread axon degeneration is an important feature of multiple sclerosis (MS) pathology and a major correlate for permanent clinical deficits. Thus, treatments that combine immunomodulatory and neuroprotective effects are beneficial for MS. Using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of MS, we recently showed that daily treatment with the phosphodiesterase 5 (PDE5) inhibitor sildenafil at peak disease rapidly ameliorates clinical symptoms and neuropathology (Pifarre et al., 2011). We have now investigated the immunomodulatory and neuroprotective actions of sildenafil treatment from the onset of EAE when the immune response prevails and show that early administration of the drug prevents disease progression. Ultrastructural analysis of spinal cord evidenced that sildenafil treatment preserves axons and myelin and increases the number of remyelinating axons. Immunostaining of oligodendrocytes at different stages of differentiation showed that sildenafil protects immature and mature myelinating oligodendrocytes. Brain-derived neurotrophic factor (BDNF), a recognized neuroprotectant in EAE, was up-regulated by sildenafil in immune and neural cells suggesting its implication in the beneficial effects of the drug. RNA microarray analysis of spinal cord revealed that sildenafil up-regulates YM-1, a marker of the alternative macrophage/microglial M2 phenotype that has neuroprotective and regenerative properties. Immunostaining confirmed up-regulation of YM-1 while the classical macrophage/microglial activation marker Iba-1 was down-regulated. Microarray analysis also showed a notable up-regulation of several members of the granzyme B cluster (GrBs). Immunostaining revealed expression of GrBs in Foxp3+-T regulatory cells (Tregs) suggesting a role for these proteases in sildenafil-induced suppression of T effector cells (Teffs). In vitro analysis of

  7. Neuroprotección en la encefalopatia hipóxico isquémica perinatal: Tratamientos con eficacia clínica demostrada y perspectivas futuras Neuroprotection in perinatal hypoxic-ischemic encephalopathy: Effective treatment and future perspectives

    Directory of Open Access Journals (Sweden)

    Agustín Legido

    2007-01-01

    present the future perspectives of other clinical and basic research investigations. Therapies with demonstrated clinical efficacy: Allopurinol: It blocks the production of free radicals following hypoxia-ischemia. In a recent study, infants with hypoplastic left heart syndrome treated with allopurinol, but not those with other congenital cardiopathies, had significantly less number of complications than controls, including death, seizures, coma or cardiac events. Opioids: In another recent study, newborns with HIE treated with morphine or phentanyl, had less severe brain damage on MRI and a better neurological outcome. Hypothermia: Both local (head cooling or systemic (whole body hypothermia have a neuroprotective effect in selected newborns with HIE, Future perspectives: Antiepileptic drugs. They have multiple mechanisms of action that can block the biochemical cascade of neuronal damage in HIE. Other therapeutic modalities. Among them the following should be emphasized: combined neuroprotective treatments, growth factors, genetic therapies, stem cell transplant, and neuroprotective immunization. In conclusión, a better knowledge of the molecular mechanisms of HIE pathogenesis and better clinical studies of neuroprotective therapies will open new possibilities aplicable to clinical practice. These advances will undoubtedly improve the prognosis of newborns with HIE.

  8. Signaling modalities during oogenesis in mammals.

    Science.gov (United States)

    McGinnis, Lynda K; Limback, S Darlene; Albertini, David F

    2013-01-01

    During oogenesis in mammals, the germ line interacts with ovarian somatic cells as follicles assemble, grow, ovulate, and die. As a result, these interactions with granulosa cells determine germ cell fate as the oocyte undergoes hypertrophy, the final stages of meiosis, and preparations required for successful fertilization. Over the past 15 years, investigators using a range of experimental approaches have uncovered the existence of multiple modalities for signaling between the oocyte and companion granulosa cells that play essential and sometimes overlapping roles during the growth and maturative phases of oogenesis. Five modalities of intercellular signaling are considered in the context of regulating oocyte gene expression, metabolism, spatial patterning, and the cell cycle. While some forms of signaling predominate at specific stages of oogenesis, such as during the assembly of primordial follicles, it is apparent that combinations of modalities work in concert to control events associated with ovulation when both nuclear and cytoplasmic maturation occur. A final key feature of the signaling platform underscoring the protracted process of oogenesis is the existence of negative and positive feedback loops designed to coordinate the tempo of oogenesis and folliculogenesis at key developmental transitions. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. New biometric modalities using internal physical characteristics

    Science.gov (United States)

    Mortenson, Juliana (Brooks)

    2010-04-01

    Biometrics is described as the science of identifying people based on physical characteristics such as their fingerprints, facial features, hand geometry, iris patterns, palm prints, or speech recognition. Notably, all of these physical characteristics are visible or detectable from the exterior of the body. These external characteristics can be lifted, photographed, copied or recorded for unauthorized access to a biometric system. Individual humans are unique internally, however, just as they are unique externally. New biometric modalities have been developed which identify people based on their unique internal characteristics. For example, "BoneprintsTM" use acoustic fields to scan the unique bone density pattern of a thumb pressed on a small acoustic sensor. Thanks to advances in piezoelectric materials the acoustic sensor can be placed in virtually any device such as a steering wheel, door handle, or keyboard. Similarly, "Imp-PrintsTM" measure the electrical impedance patterns of a hand to identify or verify a person's identity. Small impedance sensors can be easily embedded in devices such as smart cards, handles, or wall mounts. These internal biometric modalities rely on physical characteristics which are not visible or photographable, providing an added level of security. In addition, both the acoustic and impedance methods can be combined with physiologic measurements such as acoustic Doppler or impedance plethysmography, respectively. Added verification that the biometric pattern came from a living person can be obtained. These new biometric modalities have the potential to allay user concerns over protection of privacy, while providing a higher level of security.*

  10. Differential neuroprotective activity of two different grape seed extracts.

    Directory of Open Access Journals (Sweden)

    Keishi Narita

    Full Text Available Glutamate excitotoxicity is one of the major events that takes place during various neurotoxic injuries such as brain ischemia. We prepared grape seed extracts, from two different varieties, containing high amounts of polyphenols but little resveratrol. Their neuroprotective effects were investigated using primary culture of neonatal mouse hippocampal neurons treated with an excitotoxic concentration of glutamate. Koshu, a white, local variety of V. vinifera, alleviated the acute inactivation of Erk1/2 and dendrite retraction in cultured hippocampal neurons exposed to a toxic concentration of glutamate (1.0 ng/ml. By contrast, Muscat Bailey A, a red, hybrid variety (Muscat Humburg × Bailey, failed to show any neuroprotective effect. Unlike brain-derived neurotrophic factor and other neuroprotective cytokines, Koshu extract did not induce Akt phosphorylation. Koshu extract also augmented neuron survival rate 24 hours after glutamate toxicity. The comparison of polyphenols between the two samples by liquid chromatography/time-of-flight mass spectrometry demonstrated that Koshu had higher amounts of low molecular weight polyphenols along with several Koshu-specific procyanidin oligomers. These data suggest the presence of high affinity molecular targets for polyphenols in hippocampal neurons, which induce neuroprotective effects in a manner different from BDNF, and the importance of low molecular weight polyphenols and/or procyanidin oligomers for neuroprotection.

  11. The Neuroprotective Functions of Transforming Growth Factor Beta Proteins

    Directory of Open Access Journals (Sweden)

    Gábor Lovas

    2012-07-01

    Full Text Available Transforming growth factor beta (TGF-β proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed.

  12. Neuroprotection for Stroke: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Christoph Kleinschnitz

    2012-09-01

    Full Text Available Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.

  13. Inhalation gases or gaseous mediators as neuroprotectants for cerebral ischaemia.

    Science.gov (United States)

    Sutherland, Brad A; Harrison, Joanne C; Nair, Shiva M; Sammut, Ivan A

    2013-01-01

    Ischaemic stroke is one of the leading causes of morbidity and mortality worldwide. While recombinant tissue plasminogen activator can be administered to produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic benefit is only achieved in a fraction of the subset of patients eligible for fibrinolytic intervention. Neuroprotective therapies attempting to restrict the extent of brain injury following cerebral ischaemia have not been successfully translated into the clinic despite overwhelming pre-clinical evidence of neuroprotection. Therefore, an adequate treatment for the majority of acute ischaemic stroke patients remains elusive. In the stroke literature, the use of therapeutic gases has received relatively little attention. Gases such as hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess biological effects that have shown to be neuroprotective in pre-clinical models of ischaemic stroke. There are significant advantages to using gases including their relative abundance, low cost and feasibility for administration, all of which make them ideal candidates for a translational therapy for stroke. In addition, modulating cellular gaseous mediators including nitric oxide, carbon monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke therapy. Inhalation of these gaseous mediators can also produce neuroprotection, but this strategy remains to be confirmed as a viable therapy for ischaemic stroke. This review highlights the neuroprotective potential of therapeutic gas therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic advantages of gaseous therapy offer new promising directions in breaking the translational barrier for ischaemic stroke.

  14. The Neuroprotective Functions of Transforming Growth Factor Beta Proteins

    Science.gov (United States)

    Dobolyi, Arpád; Vincze, Csilla; Pál, Gabriella; Lovas, Gábor

    2012-01-01

    Transforming growth factor beta (TGF-β) proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed. PMID:22942700

  15. Multi-Modality Phantom Development

    Energy Technology Data Exchange (ETDEWEB)

    Huber, Jennifer S.; Peng, Qiyu; Moses, William W.

    2009-03-20

    Multi-modality imaging has an increasing role in the diagnosis and treatment of a large number of diseases, particularly if both functional and anatomical information are acquired and accurately co-registered. Hence, there is a resulting need for multi modality phantoms in order to validate image co-registration and calibrate the imaging systems. We present our PET-ultrasound phantom development, including PET and ultrasound images of a simple prostate phantom. We use agar and gelatin mixed with a radioactive solution. We also present our development of custom multi-modality phantoms that are compatible with PET, transrectal ultrasound (TRUS), MRI and CT imaging. We describe both our selection of tissue mimicking materials and phantom construction procedures. These custom PET-TRUS-CT-MRI prostate phantoms use agargelatin radioactive mixtures with additional contrast agents and preservatives. We show multi-modality images of these custom prostate phantoms, as well as discuss phantom construction alternatives. Although we are currently focused on prostate imaging, this phantom development is applicable to many multi-modality imaging applications.

  16. [Selection of treatment modalities in patients with spasticity].

    Science.gov (United States)

    Ota, Tetsuo

    2014-09-01

    Spasticity is the most common abnormality of muscle tone. Typically, oral antispastic drugs, phenol blocks, motor-point blocks, selective dorsal rhizotomies, and selective peripheral neurotomies are used to reduce muscle tone and/or improve ranges of motion. Recently, botulinum toxin injections and intrathecal baclofen have been used as treatment modalities. The selection of the most appropriate treatment modality by doctors treating patients with spasticity is critical. Furthermore, rehabilitation techniques, such as physiotherapy, occupational therapy, therapeutic electrical nerve stimulation, and orthosis, are useful as combination therapy for the treatment of spasticity. The purpose of this study was to outline the various modalities that are currently used for the treatment of spasticity. Regardless of the modality selected, it is imperative that treatment goals are carefully identified. The reduction of spasticity is not an appropriate treatment goal. Appropriate goals include improving gait, activities of daily living, and the quality of life.

  17. The measurement of the modal strain fields using digital shearography

    Directory of Open Access Journals (Sweden)

    Gomes J.M.

    2010-06-01

    Full Text Available This work presents a Michelson shearography interferometer configuration associated with stroboscopic double illumination technique for the measurement of modal rotation fields and their strain fields on a clamped circular aluminium plate. The speckle pattern is frozen by the synchronization between the LASER illumination and the modal vibration of the object. The quantitative evaluation is performed for each digital shearogram using a time modulation technique. The setup of double illumination LASER with out-of-plane opposite sensitivity allows the two phase maps measurement of the modal spatial gradient. The modal rotation and strain fields are extracted by the combination of this two digital phase maps. Image processing techniques are applied on the phase maps to obtain full-field measurements using a dedicated post-processing algorithm. Finally, is presented a comparison between the experimental measurement and the numerical solution.

  18. Cycling, modality styles and variation by urban environment

    DEFF Research Database (Denmark)

    Olafsson, Anton Stahl; Nielsen, Thomas Alexander Sick; Carstensen, Trine Agervig

    The aim for this study is to improve the understanding of cycling usage in relation to other modes of transport and the urban environment. Modality styles, i.e. the mode of transport or set of modes that a person habitually uses, are revealed by data on seven days transport inventory on modes......, and leisure transport are most widespread in large urban areas, while retirement and car-based transport is most abundant in small urban areas, reflecting both differences in demographics and in the urban environment. The highest mode share of cycling is in education and leisure transport modality styles...... and transport purposes from a representative sample of Danes (n=1,957). A combined factor and cluster analysis is uses to define five modality styles (education transport; public transport; retirement transport; leisure transport; and car-based transport). Modality styles categorized as education, public...

  19. Stepchild or Prodigy? Neuroprotection in Multiple Sclerosis (MS) Research.

    Science.gov (United States)

    Rottlaender, Andrea; Kuerten, Stefanie

    2015-07-01

    Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) and characterized by the infiltration of immune cells, demyelination and axonal loss. Loss of axons and nerve fiber pathology are widely accepted as correlates of neurological disability. Hence, it is surprising that the development of neuroprotective therapies has been neglected for a long time. A reason for this could be the diversity of the underlying mechanisms, complex changes in nerve fiber pathology and the absence of biomarkers and tools to quantify neuroregenerative processes. Present therapeutic strategies are aimed at modulating or suppressing the immune response, but do not primarily attenuate axonal pathology. Yet, target-oriented neuroprotective strategies are essential for the treatment of MS, especially as severe damage of nerve fibers mostly occurs in the course of disease progression and cannot be impeded by immune modulatory drugs. This review shall depict the need for neuroprotective strategies and elucidate difficulties and opportunities.

  20. Stepchild or Prodigy? Neuroprotection in Multiple Sclerosis (MS Research

    Directory of Open Access Journals (Sweden)

    Andrea Rottlaender

    2015-07-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disorder of the central nervous system (CNS and characterized by the infiltration of immune cells, demyelination and axonal loss. Loss of axons and nerve fiber pathology are widely accepted as correlates of neurological disability. Hence, it is surprising that the development of neuroprotective therapies has been neglected for a long time. A reason for this could be the diversity of the underlying mechanisms, complex changes in nerve fiber pathology and the absence of biomarkers and tools to quantify neuroregenerative processes. Present therapeutic strategies are aimed at modulating or suppressing the immune response, but do not primarily attenuate axonal pathology. Yet, target-oriented neuroprotective strategies are essential for the treatment of MS, especially as severe damage of nerve fibers mostly occurs in the course of disease progression and cannot be impeded by immune modulatory drugs. This review shall depict the need for neuroprotective strategies and elucidate difficulties and opportunities.

  1. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro...

  2. Therapeutic modality: rehabilitation of the injured athlete.

    Science.gov (United States)

    Nyland, John; Nolan, Michael F

    2004-04-01

    Traditional therapeutic modalities include cryotherapy, sonotherapy, pulsed electrical stimulation, transcutaneous electrical nerve stimulation, high-volt pulsed current, and iotopheresis. Alternative modalities include acupuncture, magnetic field therapy, biofeedback,and massage. All therapeutic modalities should be considered adjuncts to progressive functional exercise. Controlled studies rarely reach consensus regarding the efficacy of therapeutic modalities,so their use should be individualized to the patient.

  3. Modalities in homotopy type theory

    DEFF Research Database (Denmark)

    Rijke, Egbert; Shulman, Michael; Spitters, Bas

    2017-01-01

    Univalent homotopy type theory (HoTT) may be seen as a language for the category of ∞-groupoids. It is being developed as a new foundation for mathematics and as an internal language for (elementary) higher toposes. We develop the theory of factorization systems, reflective subuniverses......, and modalities in homotopy type theory, including their construction using a "localization" higher inductive type. This produces in particular the (n-connected, n-truncated) factorization system as well as internal presentations of subtoposes, through lex modalities. We also develop the semantics...

  4. Vocabulary acquisition in aphasia: Modality can matter.

    Science.gov (United States)

    Tuomiranta, Leena; Grönroos, Ann-Mari; Martin, Nadine; Laine, Matti

    2014-11-01

    The present case study investigated modality-specific aspects of novel word acquisition in aphasia. It was prompted by recent aphasia case studies indicating great interindividual variability in the ability to learn and maintain novel words in aphasia. Moreover, two previous case studies revealed a striking effect of input modality by showing effective word learning and re-learning via visual input only (Kohen, Sola, Tuomiranta, Laine, & Martin, 2012; Tuomiranta et al., 2014). The present participant TS with chronic nonfluent aphasia and post-semantic anomia was administered novel word-referent learning tasks. In the first experiment, the learning phase included simultaneous phonological and orthographic input, while the follow-up was probed separately for spoken and written responses. In the second experiment, we studied the effect of four different input and output modality combinations on her ability to learn to name the novel items. In the first experiment, TS's spoken naming performance during the learning phase was just within the range of healthy controls. Maintenance declined and remained outside that range during the whole 6-month follow-up. However, TS maintained the learned words better in written than in spoken naming throughout the follow-up, and in written naming, her maintenance stayed within the control's range up to 8 weeks post-training. The second experiment indicated that the best learning outcome was achieved with orthographic input. Orthographic input combined with orthographic output resulted in fast and accurate learning of the novel words. Interestingly, TS's test profile was opposite to her learning profile, as she repeated better than she read aloud in the linguistic background assessment. The results from the present case highlight the importance of multiple learning channels for word acquisition in individuals with aphasia. Probing the functionality of different input and output channels for learning may also prove valuable in tailoring

  5. Electrotherapy modalities for adhesive capsulitis (frozen shoulder).

    Science.gov (United States)

    Page, Matthew J; Green, Sally; Kramer, Sharon; Johnston, Renea V; McBain, Brodwen; Buchbinder, Rachelle

    2014-10-01

    Adhesive capsulitis (also termed frozen shoulder) is a common condition characterised by spontaneous onset of pain, progressive restriction of movement of the shoulder and disability that restricts activities of daily living, work and leisure. Electrotherapy modalities, which aim to reduce pain and improve function via an increase in energy (electrical, sound, light, thermal) into the body, are often delivered as components of a physical therapy intervention. This review is one in a series of reviews which form an update of the Cochrane review 'Physiotherapy interventions for shoulder pain'. To synthesise the available evidence regarding the benefits and harms of electrotherapy modalities, delivered alone or in combination with other interventions, for the treatment of adhesive capsulitis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL Plus and the ClinicalTrials.gov and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) clinical trials registries up to May 2014, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials to identify any other potentially relevant trials. We included randomised controlled trials (RCTs) and controlled clinical trials using a quasi-randomised method of allocation that included adults with adhesive capsulitis and compared any electrotherapy modality to placebo, no treatment, a different electrotherapy modality, or any other intervention. The two main questions of the review focused on whether electrotherapy modalities are effective compared to placebo or no treatment, or if they are an effective adjunct to manual therapy or exercise (or both). The main outcomes of interest were participant-reported pain relief of 30% or greater, overall pain, function, global assessment of treatment success, active shoulder abduction, quality of life, and the number of participants experiencing any adverse event. Two review authors independently selected trials for inclusion

  6. Linear contextual modal type theory

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Abstract. When one implements a logical framework based on linear type theory, for example the Celf system [?], one is immediately con- fronted with questions about their equational theory and how to deal with logic variables. In this paper, we propose linear contextual modal type theory that gives...

  7. Fetal Neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application

    Directory of Open Access Journals (Sweden)

    Clément Chollat

    2018-04-01

    Full Text Available Despite improvements in perinatal care, preterm birth still occurs regularly and the associated brain injury and adverse neurological outcomes remain a persistent challenge. Antenatal magnesium sulfate administration is an intervention with demonstrated neuroprotective effects for preterm births before 32 weeks of gestation (WG. Owing to its biological properties, including its action as an N-methyl-d-aspartate receptor blocker and its anti-inflammatory effects, magnesium is a good candidate for neuroprotection. In hypoxia models, including hypoxia-ischemia, inflammation, and excitotoxicity in various species (mice, rats, pigs, magnesium sulfate preconditioning decreased the induced lesions’ sizes and inflammatory cytokine levels, prevented cell death, and improved long-term behavior. In humans, some observational studies have demonstrated reduced risks of cerebral palsy after antenatal magnesium sulfate therapy. Meta-analyses of five randomized controlled trials using magnesium sulfate as a neuroprotectant showed amelioration of cerebral palsy at 2 years. A meta-analysis of individual participant data from these trials showed an equally strong decrease in cerebral palsy and the combined risk of fetal/infant death and cerebral palsy at 2 years. The benefit remained similar regardless of gestational age, cause of prematurity, and total dose received. These data support the use of a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h to avoid potential deleterious effects. Antenatal magnesium sulfate is now recommended by the World Health Organization and many pediatric and obstetrical societies, and it is requisite to maximize its administration among women at risk of preterm delivery before 32 WG.

  8. Role modalities in Urban Health Education

    DEFF Research Database (Denmark)

    Wistoft, Karen

    2011-01-01

    food, drinking alcohol, smoking cigarettes or having sexual relationships, the children are brought into a moral, political and lifestyle oriented discourse on risks. In this discourse their identity (as children or adolescents) is at stake as they are expected to participate as well...... educators and other key persons related children and adolescent (N=34). The paper takes upon it self a combined search for different role modalities of present health semantics aimed at children and young people. The relations between health semantics, citizen roles, and educational inclusion......), and on the other hand as a semantic preparation for participation in behavioural activities such as co-decision making, different preventive initiatives are analysed. The theoretical framework combines elements from system theory (Luhmann, 1995a), pedagogical studies and health education theory in order to grasp...

  9. Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.

    Science.gov (United States)

    Nafissi, Nafiseh; Foldvari, Marianna

    2015-01-01

    Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

  10. The Neuroprotection Effect of Oxygen Therapy: A Systematic Review ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... OR “acute ischemic stroke (AIS)” OR “TBI” AND. “Clinical trial”. We also reviewed the .... Table 1: Characteristics of studies that compared normobaric oxygen treatment and controls in stroke patients. Study Year Study design ...... Young AR, Ali C, Duretête A, Vivien D. Neuroprotection and stroke: Time for a ...

  11. Neuroprotective peptides as drug candidates against Alzheimer's diasease

    Czech Academy of Sciences Publication Activity Database

    Patočka, J.; Slaninová, Jiřina; Kunešová, G.

    2005-01-01

    Roč. 3, - (2005), 67-73 ISSN 1214-021X R&D Projects: GA ČR(CZ) GA305/03/1100 Institutional research plan: CEZ:AV0Z40550506 Keywords : Alzheimers 's disease * neuroprotective peptide * Abeta peptide Subject RIV: CE - Biochemistry

  12. NEUROPROTECTIVE THERAPIES IN GLAUCOMA: II. GENETIC NANOTECHNOLOGY TOOLS

    Directory of Open Access Journals (Sweden)

    Nafiseh eNafissi

    2015-10-01

    Full Text Available Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The field of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

  13. Multiple sclerosis: Neuroprotective alliance of estrogen-progesterone and gender

    NARCIS (Netherlands)

    Kipp, M.; Amor, S.; Kraut, R.; Beyer, C.

    2012-01-01

    The potential of 17β-estradiol and progesterone as neuroprotective factors is well-recognized. Persuasive data comes from in vitro and animal models reflecting a wide range of CNS disorders. These studies have endeavored to translate findings into human therapies. Nonetheless, few human studies show

  14. Neuroprotective potential of Citrullus lanatus seed extract and ...

    African Journals Online (AJOL)

    Mercury chloride toxicity continues to be relevant in the advent of increased interest in mining activity in Nigeria. The neuroprotective potential of Citrullus lanatus seed extract (CLSE) (Watermelon seed) and vitamin E (VIT E) on mercury chloride intoxication on the frontal cerebral cortex of male rats was investigated.

  15. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    edoja

    2013-07-31

    Jul 31, 2013 ... management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity. Key words: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection. INTRODUCTION. Propionic acid (PA) is a short chain fatty acid that is dietary obtained (Zarate ...

  16. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    With sufficient research and clinical trials in future, this could prove to be successful in treatment or management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity. Keywords: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection. African Journal ...

  17. Neuroprotective effects of α-lipoic acid against hypoxic– ischemic ...

    African Journals Online (AJOL)

    Purpose: To explore the neuroprotective efficacy of α-lipoic acid (ALA) against hypoxic-ischemic encephalopathy (HIE) in neonatal rats. Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: group I received saline; group II (HI) underwent unilateral carotid artery ligation and hypoxia (92 % N2 ...

  18. Metallothioneins I and II: neuroprotective significance during CNS pathology

    DEFF Research Database (Denmark)

    Penkowa, Milena; Stankovic, Roger; Chung, Roger

    2006-01-01

    expression across animal phyla suggests that MTs may play an important physiological role, MT-I, II knock out (KO) mice survive to adulthood. In both central and peripheral nervous tissues, MT-I, II have neuroprotective roles, which are also induced by exogenous MT-I and/or MT-II treatment. Hence, MT-I, II...

  19. Putative neuroprotective actions of N-acyl-ethanolamines

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Moesgaard, B.; Petersen, G.

    2002-01-01

    when other phospholipids are subjected to rapid degradation. This is an important biosynthetic aspect of NAPE and NAE, as NAEs may be neuroprotective by a number of different mechanisms involving both receptor activation and non-receptor-mediated effects, e.g. by binding to cannabinoid receptors...

  20. Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain ...

    African Journals Online (AJOL)

    Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 ...

  1. Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

    Science.gov (United States)

    Hernández, Cristina; Simó, Rafael

    2016-01-01

    Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed. PMID:27123463

  2. The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic ...

    African Journals Online (AJOL)

    The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic Stroke In Animal Model: A Review. ... Conclusion: An awareness of the benefits of acupuncture might lead more patients into accepting acupuncture therapy for the management of patients with ischemic stroke and patients with high risk of ischemic stroke.

  3. Neuroprotective effect of Terminalia chebula extracts and ellagic ...

    African Journals Online (AJOL)

    Background: Alzheimer's disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aβ25-35)-induced cell toxicity ...

  4. Neuroprotective effect corilagin in spinal cord injury rat model by ...

    African Journals Online (AJOL)

    Background: Neurological functions get altered in a patient suffering from spinal cord injury (SCI). Present study evaluates the neuroprotective effect of corilagin in spinal cord injury rats by inhibiting nuclear factor-kappa B (NF-κB), inflammatory mediators and apoptosis. Materials and method: Spinal cord injury was ...

  5. Melatonin-sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a 'drug-prodrug' mechanism of action.

    Science.gov (United States)

    Egea, Javier; Buendia, Izaskun; Parada, Esther; Navarro, Elisa; Rada, Patricia; Cuadrado, Antonio; López, Manuela G; García, Antonio G; León, Rafael

    2015-04-01

    Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties. Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug-prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia. ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2-antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production. ITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases. © 2014 The British Pharmacological Society.

  6. Melatonin for women in pregnancy for neuroprotection of the fetus.

    Science.gov (United States)

    Wilkinson, Dominic; Shepherd, Emily; Wallace, Euan M

    2016-03-29

    Melatonin is an antioxidant with anti-inflammatory and anti-apoptotic effects. Animal studies have supported a fetal neuroprotective role for melatonin when administered maternally. It is important to assess whether melatonin, given to the mother, can reduce the risk of neurosensory disabilities (including cerebral palsy) and death, associated with fetal brain injury, for the preterm or term compromised fetus. To assess the effects of melatonin when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016). We planned to include randomised controlled trials and quasi-randomised controlled trials comparing melatonin given to women in pregnancy (regardless of the route, timing, dose and duration of administration) for fetal neuroprotection with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of melatonin. Two review authors planned to independently assess trial eligibility, trial quality and extract the data. We found no randomised trials for inclusion in this review. One study is ongoing. As we did not identify any randomised trials for inclusion in this review, we are unable to comment on implications for practice at this stage.Although evidence from animals studies has supported a fetal neuroprotective role for melatonin when administered to the mother during pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant women have been completed to date. However, there is currently one ongoing randomised controlled trial (with an estimated enrolment target of 60 pregnant women) which examines the dose of melatonin, administered to women at risk of imminent very preterm birth (less than 28 weeks' gestation) required to reduce brain damage in the white matter of the babies that were born very preterm.Further high-quality research is needed and research

  7. A Modal Model to Simulate Typical Structural Dynamic Nonlinearity [PowerPoint

    Energy Technology Data Exchange (ETDEWEB)

    Mayes, Randall L.; Pacini, Benjamin Robert; Roettgen, Dan

    2016-01-01

    Some initial investigations have been published which simulate nonlinear response with almost traditional modal models: instead of connecting the modal mass to ground through the traditional spring and damper, a nonlinear Iwan element was added. This assumes that the mode shapes do not change with amplitude and there are no interactions between modal degrees of freedom. This work expands on these previous studies. An impact experiment is performed on a structure which exhibits typical structural dynamic nonlinear response, i.e. weak frequency dependence and strong damping dependence on the amplitude of vibration. Use of low level modal test results in combination with high level impacts are processed using various combinations of modal filtering, the Hilbert Transform and band-pass filtering to develop response data that are then fit with various nonlinear elements to create a nonlinear pseudo-modal model. Simulations of forced response are compared with high level experimental data for various nonlinear element assumptions.

  8. Phase II Trial of Combined Modality Therapy With Concurrent Topotecan Plus Radiotherapy Followed by Consolidation Chemotherapy for Unresectable Stage III and Selected Stage IV Non-Small-Lung Cancer

    International Nuclear Information System (INIS)

    Seung, Steven K.; Ross, Helen J.

    2009-01-01

    Purpose: The optimal combination of chemotherapy and radiotherapy (RT) and the role of consolidation chemotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC) are unknown. Topotecan is active against NSCLC, can safely be combined with RT at effective systemic doses, and can be given by continuous infusion, making it an attractive study agent against locally advanced NSCLC. Methods and Materials: In this pilot study, 20 patients were treated with infusion topotecan 0.4 mg/m 2 /d with three-dimensional conformal RT to 63 Gy both delivered Monday through Friday for 7 weeks. Patients without progression underwent consolidation chemotherapy with etoposide and a platinum agent for one cycle followed by two cycles of docetaxel. The study endpoints were treatment response, time to progression, survival, and toxicity. Results: Of the 20 patients, 19 completed induction chemoradiotherapy and 13 completed consolidation. Of the 20 patients, 18 had a partial response and 1 had stable disease after induction chemoradiotherapy. The 3-year overall survival rate was 32% (median, 18 months). The local and distant progression-free survival rate was 30% (median, 21 months) and 58% (median, not reached), respectively. Three patients developed central nervous system metastases, 1 within 228 days, 1 within 252 days, and 1 within 588 days. Three patients had pulmonary emboli. Therapy was well tolerated with 1 of 20 developing Grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17 of 20 patients but was not clinically significant. Other Grade 3 toxicities included esophagitis in 3, esophageal stricture in 2, fatigue in 8, and weight loss in 1. Grade 3 pneumonitis occurred in 6 of 20 patients. Conclusion: Continuous infusion topotecan with RT was well tolerated and active in the treatment of poor-risk patients with unresectable Stage III NSCLC

  9. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

    Science.gov (United States)

    Nadal, Xavier; Del Río, Carmen; Casano, Salvatore; Palomares, Belén; Ferreiro-Vera, Carlos; Navarrete, Carmen; Sánchez-Carnerero, Carolina; Cantarero, Irene; Bellido, Maria Luz; Meyer, Stefan; Morello, Gaetano; Appendino, Giovanni; Muñoz, Eduardo

    2017-12-01

    Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing and storage. While the biological effects of decarboxylated cannabinoids such as Δ 9 -tetrahydrocannabinol have been extensively investigated, the bioactivity of Δ 9 -tetahydrocannabinol acid (Δ 9 -THCA) is largely unknown, despite its occurrence in different Cannabis preparations. Here we have assessed possible neuroprotective actions of Δ 9 -THCA through modulation of PPARγ pathways. The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ 9 -THCA on mitochondrial biogenesis and PPARγ coactivator 1-α expression was investigated in Neuro-2a (N2a) cells. The neuroprotective effect was analysed in STHdh Q111/Q111 cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). The in vivo neuroprotective activity of Δ 9 -THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NPA). Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ 9 -THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in STHdh Q111/Q111 cells and by mutHtt-q94 in N2a cells. Δ 9 -THCA, through a PPARγ-dependent pathway, was neuroprotective in mice treated with 3-NPA, improving motor deficits and preventing striatal degeneration. In addition, Δ 9 -THCA attenuated microgliosis, astrogliosis and up-regulation of proinflammatory markers induced by 3-NPA. Δ 9 -THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases. © 2017 The British Pharmacological Society.

  10. Neuroprotection with hypothermia and allopurinol in an animal model of hypoxic-ischemic injury: Is it a gender question?

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez-Fanjul

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is one of the most important causes of neonatal brain injury. Therapeutic hypothermia (TH is the standard treatment for term newborns after perinatal hypoxic ischemic injury (HI. Despite this, TH does not provide complete neuroprotection. Allopurinol seems to be a good neuroprotector in several animal studies, but it has never been tested in combination with hypothermia. Clinical findings show that male infants with (HI fare more poorly than matched females in cognitive outcomes. However, there are few studies about neuroprotection taking gender into account in the results. The aim of the present study was to evaluate the potential additive neuroprotective effect of allopurinol when administrated in association with TH in a rodent model of moderate HI. Gender differences in neuroprotection were also evaluated.P10 male and female rat pups were subjected to HI (Vannucci model and randomized into five groups: sham intervention (Control, no treatment (HI, hypothermia (HIH, allopurinol (HIA, and dual therapy (hypothermia and allopurinol (HIHA. To evaluate a treatment's neuroprotective efficiency, 24 hours after the HI event caspase3 activation was measured. Damaged area and hippocampal volume were also measured 72 hours after the HI event. Negative geotaxis test was performed to evaluate early neurobehavioral reflexes. Learning and spatial memory were assessed via Morris Water Maze (MWM test at 25 days of life.Damaged area and hippocampal volume were different among treatment groups (p = 0.001. The largest tissue lesion was observed in the HI group, followed by HIA. There were no differences between control, HIH, and HIHA. When learning process was analyzed, no differences were found. Females from the HIA group had similar results to the HIH and HIHA groups. Cleaved caspase 3 expression was increased in both HI and HIA. Despite this, in females cleaved caspase-3 was only differently increased in the HI group. All

  11. Anesthetic neuroprotection: antecedents and an appraisal of preclinical and clinical data quality.

    Science.gov (United States)

    Ishida, Kazuyoshi; Berger, Miles; Nadler, Jacob; Warner, David S

    2014-01-01

    Anesthetics have been studied for nearly fifty years as potential neuroprotective compounds in both perioperative and resuscitation medicine. Although anesthetics present pharmacologic properties consistent with preservation of brain viability in the context of an ischemic insult, no anesthetic has been proven efficacious for neuroprotection in humans. After such effort, it could be concluded that anesthetics are simply not neuroprotective in humans. Moreover, pharmacologic neuroprotection with non-anesthetic drugs has also repeatedly failed to be demonstrated in human acute brain injury. Recent focus has been on rectification of promising preclinical neuroprotection data and subsequent failed clinical trials. This has led to consensus guidelines for the process of transferring purported therapeutics from bench to bedside. In this review we first examined the history of anesthetic neuroprotection research. Then, a systematic review was performed to identify major clinical trials of anesthetic neuroprotection. Both the preclinical neuroprotection portfolio cited to justify a clinical trial and the design and conduct of that clinical trial were evaluated using modern standards that include the Stroke Therapy Academic Industry Roundtable (STAIR) and Consolidated Standards of Reporting Trials (CONSORT) guidelines. In publications intended to define anesthetic neuroprotection, we found overall poor quality of both preclinical efficacy analysis portfolios and clinical trial designs and conduct. Hence, using current translational research standards, it was not possible to conclude from existing data whether anesthetics ameliorate perioperative ischemic brain injury. Incorporation of advances in translational neuroprotection research conduct may provide a basis for more definitive and potentially successful clinical trials of anesthetics as neuroprotectants.

  12. Imaging Modalities for Cervical Spondylotic Stenosis and Myelopathy

    Directory of Open Access Journals (Sweden)

    C. Green

    2012-01-01

    Full Text Available Cervical spondylosis is a spectrum of pathology presenting as neck pain, radiculopathy, and myelopathy or all in combination. Diagnostic imaging is essential to diagnosis and preoperative planning. We discuss the modalities of imaging in common practice. We examine the use of imaging to differentiate among central, subarticular, and lateral stenosis and in the assessment of myelopathy.

  13. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  14. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  15. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  16. Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

    Science.gov (United States)

    Tazik, Shawna; Johnson, Shakevia; Lu, Deyin; Johnson, Chandra; Youdim, Moussa B. H.; Stockmeier, Craig A.

    2009-01-01

    Stress can affect the brain and lead to depression; however, the molecular pathogenesis is unclear. An association between stress and stress-induced hypersecretion of glucocorticoids occurs during stress. Dexamethasone (a synthetic glucocorticoid steroid) has been reported to induce apoptosis and increase the activity of monoamine oxidase (MAO) (Youdim et al. 1989). MAO is an enzyme for the degradation of aminergic neurotransmitters; dopamine, noradrenaline and serotonin and dietary amines and MAO inhibitors are classical antidepressant drugs. In this study, we have compared the ability of rasagiline (Azilect) and its main metabolite, R-aminoindan with selegiline (Deprenyl) in prevention of dexamethasone-induced brain cell death employing human neuroblastoma SH-SY5Y cells and glioblastoma 1242-MG cells. Dexamethasone reduced cell viability as measured by MTT test, but rasagiline, selegiline, and 1-R-aminoindan could significantly prevent dexamethasone-induced brain cell death. Among three drugs, rasagiline had the highest neuroprotective effect. Furthermore, the inhibitory effects of these drugs on MAOB catalytic activity and on apoptotic DNA damage (TUNEL staining) were examined. Rasagiline exhibited highest inhibition on MAO B enzymatic activity and prevention on DNA damage as compared to selegiline and 1-R-aminoindan. In summary, the greater neuroprotective effect of rasagiline may be associated with the combination of the parent drug and its metabolite 1-R-aminoindan. PMID:19384601

  17. Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury.

    Directory of Open Access Journals (Sweden)

    Long-Xia Chen

    Full Text Available Periventricular leukomalacia (PVL is a common ischemic brain injury in premature infants for which there is no effective treatment. The objective of this study was to determine whether transplanted mouse oligodendrocyte progenitor cells (OPCs have neuroprotective effects in a rat model of PVL. Hypoxia-ischemia (HI was induced in 3-day-old rat pups by left carotid artery ligation, followed by exposure to 6% oxygen for 2.5 h. Animals were assigned to OPC transplantation or sham control groups and injected with OPCs or PBS, respectively, and sacrificed up to 6 weeks later for immunohistochemical analysis to investigate the survival and differentiation of transplanted OPCs. Apoptosis was evaluated by double immunolabeling of brain sections for caspase-3 and neuronal nuclei (NeuN, while proliferation was assessed using a combination of anti-Nestin and -bromodeoxyuridine antibodies. The expression of brain-derived neurotrophic factor (BDNF and Bcl-2 was examined 7 days after OPC transplantation. The Morris water maze was used to test spatial learning and memory. The results showed that transplanted OPCs survived and formed a myelin sheath, and stimulated BDNF and Bcl-2 expression and the proliferation of neural stem cells (NSC, while inhibiting HI-induced neuronal apoptosis relative to control animals. Moreover, deficits in spatial learning and memory resulting from HI were improved by OPC transplantation. These results demonstrate an important neuroprotective role for OPCs that can potentially be exploited in cell-based therapeutic approaches to minimize HI-induced brain injury.

  18. Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems.

    Directory of Open Access Journals (Sweden)

    Mireia Herrando-Grabulosa

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology, we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.

  19. Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Masataka Nakajima

    2017-09-01

    Full Text Available Interleukin (IL-10 is a contributing factor to neuroprotection of mesenchymal stem cell (MSC transplantation after ischemic stroke. Our aim was to increase therapeutic effects by combining MSCs and ex vivo IL-10 gene transfer with an adeno-associated virus (AAV vector using a rat transient middle cerebral artery occlusion (MCAO model. Sprague-Dawley rats underwent 90 min MCAO followed by intravenous administration of MSCs alone or IL-10 gene-transferred MSCs (MSC/IL-10 at 0 or 3 hr after ischemia reperfusion. Infarct lesions, neurological deficits, and immunological analyses were performed within 7 days after MCAO. 0-hr transplantation of MSCs alone and MSC/IL-10 significantly reduced infarct volumes and improved motor function. Conversely, 3-hr transplantation of MSC/IL-10, but not MSCs alone, significantly reduced infarct volumes (p < 0.01 and improved motor function (p < 0.01 compared with vehicle groups at 72 hr and 7 days after MCAO. Immunological analysis showed that MSC/IL-10 transplantation significantly inhibits microglial activation and pro-inflammatory cytokine expression compared with MSCs alone. Moreover, overexpressing IL-10 suppressed neuronal degeneration and improved survival of engrafted MSCs in the ischemic hemisphere. These results suggest that overexpressing IL-10 enhances the neuroprotective effects of MSC transplantation by anti-inflammatory modulation and thereby supports neuronal survival during the acute ischemic phase.

  20. Sensory stimulation for lowering intraocular pressure, improving blood flow to the optic nerve and neuroprotection in primary open-angle glaucoma.

    Science.gov (United States)

    Rom, Edith

    2013-12-01

    Primary open-angle glaucoma is a group of optic neuropathies that can lead to irreversible blindness. Sensory stimulation in the form of acupuncture or ear acupressure may contribute to protecting patients from blindness when used as a complementary method to orthodox treatment in the form of drops, laser or surgery. The objective of this article is to provide a narrative overview of the available literature up to July 2012. It summarises reported evidence on the potential beneficial effects of sensory stimulation for glaucoma. Sensory stimulation appears to significantly enhance the pressure-lowering effect of orthodox treatments. Studies suggest that it may also improve blood flow to the eye and optic nerve head. Furthermore, it may play a role in neuroprotection through regulating nerve growth factor and brain-derived neurotrophic factor and their receptors, thereby encouraging the survival pathway in contrast to the pathway to apoptosis. Blood flow and neuroprotection are areas that are not directly influenced by orthodox treatment modalities. Numerous different treatment protocols were used to investigate the effect of sensory stimulation on intraocular pressure, blood flow or neuroprotection of the retina and optic nerve in the animal model and human pilot studies. Objective outcomes were reported to have been evaluated with Goldmann tonometry, Doppler ultrasound techniques and electrophysiology (pattern electroretinography, visually evoked potentials), and supported with histological studies in the animal model. Taken together, reported evidence from these studies strongly suggests that sensory stimulation is worthy of further research.

  1. Timing flickers across sensory modalities.

    Science.gov (United States)

    Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Anna Maria; Oliveri, Massimiliano

    2009-01-01

    In tasks requiring a comparison of the duration of a reference and a test visual cue, the spatial position of test cue is likely to be implicitly coded, providing a form of a congruency effect or introducing a response bias according to the environmental scale or its vectorial reference. The precise mechanism generating these perceptual shifts in subjective duration is not understood, although several studies suggest that spatial attentional factors may play a critical role. Here we use a duration comparison task within and across sensory modalities to examine if temporal performance is also modulated when people are exposed to spatial distractors involving different sensory modalities. Different groups of healthy participants performed duration comparison tasks in separate sessions: a time comparison task of visual stimuli during exposure to spatially presented auditory distractors; and a time comparison task of auditory stimuli during exposure to spatially presented visual distractors. We found the duration of visual stimuli biased depending on the spatial position of auditory distractors. Observers underestimated the duration of stimuli presented in the left spatial field, while there was an overestimation trend in estimating the duration of stimuli presented in the right spatial field. In contrast, timing of auditory stimuli was unaffected by exposure to visual distractors. These results support the existence of multisensory interactions between space and time showing that, in cross-modal paradigms, the presence of auditory distractors can modify visuo-temporal perception but not vice versa. This asymmetry is discussed in terms of sensory perceptual differences between the two systems.

  2. Potential Therapeutic Modalities in Cancer Gene Therapy

    Directory of Open Access Journals (Sweden)

    Prithvi Sinha

    2017-04-01

    Full Text Available In spite of huge concerted efforts, the treatment of cancer, a disease frequently associated with genetic alterations caused due to hereditary or environmental factors, remains a challenge. The last few years have witnessed emergence of several innovative and effective modalities for the treatment of solid tumours and hematological malignancies. Gene therapy has shown enormous potential for cancer treatment, especially for metastatic cancers which unlike localized solid tumours, may not be amenable to surgery or other treatment options. Gene therapy aims to introduce a correct copy of the malfunctioning gene in the tumour environment by using viral or non-viral methods to impede or inhibit its growth. This review provides an overview of three main approaches for cancer gene therapy namely immunotherapy, oncolytic therapy and gene transfer therapy. Immunotherapy augments the host immune system in order to destroy cancer cells while oncolytic therapy uses genetically engineered viruses such as to effectively kill cancer cells. Clinical studies so far have shown that cells can be engineered to express gene products that can specifically target cancer cells and prevents their growth and metastasis. Though gene therapy for cancer is yet to see extensive clinical use, it is likely that in combination with other treatment modalities, it will help in controlling and possibly curing cancer in the near future.

  3. Don Cossack Army Charters of the Mid 18th Century Via the Category of Modality

    Directory of Open Access Journals (Sweden)

    Elena Mihaylovna Sheptukhina

    2015-12-01

    Full Text Available The article deals with the language means of modality in the texts of military charters of the mid 18th cent. from the "Mikhailovsky stanitza hetman" archive (State Achieve of Volgograd Region. Military charters used to be major documents of legislation within Don Cossack Host, as being at that time an administrative unit in the territory of Russian Empire. The results of the contextual analysis verify the following facts: the charter texts are mainly characterized by an imperative tone of regulation that is caused by coordination between dominant meanings of a propositional (situational modality of necessity and pragmatic modality of volition, that are thought to be interrelated in utterances. The modal meaning of necessity is marked by the verbal construction with an independent infinitive or the combinations of modal verbs (imet' / possess; nadlezhat' / be to, modal predicatives with a dependent infinitive (dolzhen, nadobno, etc. / must (have to. Modality of volition is presented with a set of lexical units that possess the meanings of ordering, permission, offers, verbal forms that are used as performatives, or point to the status of a subject, etc. The texts under study represent some other modal meanings: possibility (with the words moch' / be able to; mozhno / could / may combined with an infinitive, in subordinate clauses with a particle li (if / wether, etc. in an interrogative clauses. In complex sentences with subordination combinations of various modal meanings are observed.

  4. Extract of Antrodia camphorata Exerts Neuroprotection against Embolic Stroke in Rats without Causing the Risk of Hemorrhagic Incidence

    Directory of Open Access Journals (Sweden)

    Ye-Ming Lee

    2014-01-01

    Full Text Available In this study, the neuroprotective effect of an extract of Antrodia camphorata (A. camphorata, a fungus commonly used in Chinese folk medicine for treatment of viral hepatitis and cancer, alone or in combination with aspirin was investigated in a rat embolic stroke model. An ischemic stroke was induced in rats by a selective occlusion of the middle cerebral artery (MCA with whole blood clots and then orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone and combined with aspirin (5 mg/kg/day. Sixty days later, the brains were removed, sectioned, and stained with triphenyltetrazolium chloride and analysed by a commercial image processing software program. Brain infarct volume, neurobehavioral score, cerebral blood perfusion, and subarachnoid and intracerebral hemorrhage incidence were perceived. In addition, potential bleeding side effect of the combinative therapy was assessed by measuring hemoglobin (Hb content during intracerebral hemorrhage and gastric bleeding, prothrombin time (PT, and occlusion time (OT after oral administration. Posttreatment with high dose A. camphorata significantly reduced infarct volume and improved neurobehavioral score (P < 0.05. Since A. camphorata alone or with aspirin did not alter the Hb level, this treatment is safe and does not cause hemorrhagic incident. Remarkably, the combination of A. camphorata and aspirin did not show a significant effect on the bleeding time, PT and OT increase suggesting that A. camphorata may have the neuroprotective effect without the prolongation of bleeding time or coagulation time. From these observations, we suggest that combinative therapy of A. camphorata and aspirin might offer enhanced neuroprotective efficacies without increasing side effects.

  5. Cycling, modality styles and variation by urban environment

    OpenAIRE

    Olafsson, Anton Stahl; Nielsen, Thomas Alexander Sick; Carstensen, Trine Agervig

    2013-01-01

    The aim for this study is to improve the understanding of cycling usage in relation to other modes of transport and the urban environment. Modality styles, i.e. the mode of transport or set of modes that a person habitually uses, are revealed by data on seven days transport inventory on modes and transport purposes from a representative sample of Danes (n=1,957). A combined factor and cluster analysis is uses to define five modality styles (education transport; public transport; retirement tr...

  6. Special issue on Operational Modal Analysis

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Brincker, Rune

    2010-01-01

    Operational Modal Analysis (OMA) is not really a new discipline; it has been present from the very beginning of the development of modal testing and analysis going back to the sixties and early seventies.......Operational Modal Analysis (OMA) is not really a new discipline; it has been present from the very beginning of the development of modal testing and analysis going back to the sixties and early seventies....

  7. Bimodal extinction without cross-modal extinction.

    OpenAIRE

    Inhoff, A W; Rafal, R D; Posner, M J

    1992-01-01

    Three patients with unilateral neurological injury were clinically examined. All showed consistent unilateral extinction in the tactile and visual modalities on simultaneous intramodal stimulation. There was virtually no evidence for cross-modal extinction, however, so that contralateral stimulation of one modality would have extinguished perception of ipsilateral stimuli in the other modality. It is concluded that the attentional system controlling the encoding of tactile and visual stimuli ...

  8. Modal Subordination in Type Theoretic Dynamic Logic

    OpenAIRE

    Qian, Sai; De Groote, Philippe; Amblard, Maxime

    2016-01-01

    International audience; Classical theories of discourse semantics, such as Discourse Representation Theory (DRT), Dynamic Predicate Logic (DPL), predict that an indefinite noun phrase cannot serve as antecedent for an anaphor if the noun phrase is, but the anaphor is not, in the scope of a modal expression. However, this prediction meets with counterexamples. The phenomenon modal subordination is one of them. In general, modal subordination is concerned with more than two modalities, where th...

  9. Modal strain energies in COSMIC NASTRAN

    Science.gov (United States)

    Snyder, B. D.; Venkayya, V. B.

    1989-01-01

    A computer program was developed to take a NASTRAN output file from a normal modes analysis and calculate the modal strain energies of selected elements. The FORTRAN program can determine the modal strain energies for CROD, CBAR, CELAS, CTRMEM, CQDMEM2, and CSHEAR elements. Modal strain energies are useful in estimating damping in structures.

  10. Completeness for flat modal fixpoint logics

    NARCIS (Netherlands)

    Santocanale, L.; Venema, Y.

    2010-01-01

    This paper exhibits a general and uniform method to prove axiomatic completeness for certain modal fixpoint logics. Given a set Γ of modal formulas of the form γ(x,p1,…,pn), where x occurs only positively in γ, we obtain the flat modal fixpoint language L♯(Γ) by adding to the language of polymodal

  11. In vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine : Combined therapy and temporal course of protection

    NARCIS (Netherlands)

    Stuiver, BT; Douma, BRK; Bakker, R; Nyakas, C; Luiten, PGM

    Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective

  12. Independent modal space control with positive position feedback

    Science.gov (United States)

    Baz, A.; Poh, S.; Fedor, J.

    1989-01-01

    An independent modal space control (IMSC) algorithm is presented, whose modal control forces are generated from a positive position feedback (PPF) strategy. The proposed algorithm combines the attributes of both the IMSC and the PPF, and maintains the simplicity of the IMSC as it designs the controller of a complex structure at the uncoupled modal level. The effectiveness of the algorithm in damping out the vibration of flexible structures is validated experimentally. A simple cantilevered beam is employed as an example of a flexible structure whose multimodes of vibration are controlled by a single actuator. Performance of the active control system is determined in the frequency and the time domains. The experimental results indicate the potential of the proposed methodology as a viable method for controlling the vibration of large flexible structures.

  13. Vibration fatigue using modal decomposition

    Science.gov (United States)

    Mršnik, Matjaž; Slavič, Janko; Boltežar, Miha

    2018-01-01

    Vibration-fatigue analysis deals with the material fatigue of flexible structures operating close to natural frequencies. Based on the uniaxial stress response, calculated in the frequency domain, the high-cycle fatigue model using the S-N curve material data and the Palmgren-Miner hypothesis of damage accumulation is applied. The multiaxial criterion is used to obtain the equivalent uniaxial stress response followed by the spectral moment approach to the cycle-amplitude probability density estimation. The vibration-fatigue analysis relates the fatigue analysis in the frequency domain to the structural dynamics. However, once the stress response within a node is obtained, the physical model of the structure dictating that response is discarded and does not propagate through the fatigue-analysis procedure. The structural model can be used to evaluate how specific dynamic properties (e.g., damping, modal shapes) affect the damage intensity. A new approach based on modal decomposition is presented in this research that directly links the fatigue-damage intensity with the dynamic properties of the system. It thus offers a valuable insight into how different modes of vibration contribute to the total damage to the material. A numerical study was performed showing good agreement between results obtained using the newly presented approach with those obtained using the classical method, especially with regards to the distribution of damage intensity and critical point location. The presented approach also offers orders of magnitude faster calculation in comparison with the conventional procedure. Furthermore, it can be applied in a straightforward way to strain experimental modal analysis results, taking advantage of experimentally measured strains.

  14. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    Science.gov (United States)

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

    2015-01-01

    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

  15. Neuroprotective effects of Resveratrol in Alzheimer Disease Pathology

    Directory of Open Access Journals (Sweden)

    Shraddha D Rege

    2014-09-01

    Full Text Available Alzheimer’s disease (AD is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4’-trihydroxy-trans-stilbene when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogues aimed at increasing bioavailability in plasma is also discussed.

  16. [Similarity of cycloprolylglycine to piracetam in antihypoxic and neuroprotective effects].

    Science.gov (United States)

    Kolisnikova, K N; Gudasheva, T A; Nazarova, G A; Antipov, T A; Voronina, T A; Seredenin, S B

    2012-01-01

    The antihypoxic activity of the endogenous cyclic dipeptide cycloprolylglycine (CPG) has been studied on a model of normobaric hypoxia with hypercapnia and its neuroprotective activity has been studied on a model of human neuroblastoma SH-SY5Y cell damage by 6-hydroxydopamine. It is established that CPG exhibits the antihypoxic activity at doses of 0.5 and 1.0 mg/kg (i.p.) on outbred and BALB/c mice, but not on C57B1/6 mice. The neuroprotective activity of CPG was detected in 10(-5) - 10(-8) M concentration range only when the treatment was carried out 24h before toxin introduction. The obtained data confirm the hypothesis that piracetam is a mimetic of the endogenous CPG neuropeptide.

  17. Electrotherapy modalities for rotator cuff disease.

    Science.gov (United States)

    Page, Matthew J; Green, Sally; Mrocki, Marshall A; Surace, Stephen J; Deitch, Jessica; McBain, Brodwen; Lyttle, Nicolette; Buchbinder, Rachelle

    2016-06-10

    , quality of life and the number of participants experiencing adverse events. Two review authors independently selected trials for inclusion, extracted the data, performed a risk of bias assessment and assessed the quality of the body of evidence for the main outcomes using the GRADE approach. We included 47 trials (2388 participants). Most trials (n = 43) included participants with rotator cuff disease without calcification (four trials included people with calcific tendinitis). Sixteen (34%) trials investigated the effect of an electrotherapy modality delivered in isolation. Only 23% were rated at low risk of allocation bias, and 49% were rated at low risk of both performance and detection bias (for self-reported outcomes). The trials were heterogeneous in terms of population, intervention and comparator, so none of the data could be combined in a meta-analysis.In one trial (61 participants; low quality evidence), pulsed therapeutic ultrasound (three to five times a week for six weeks) was compared with placebo (inactive ultrasound therapy) for calcific tendinitis. At six weeks, the mean reduction in overall pain with placebo was -6.3 points on a 52-point scale, and -14.9 points with ultrasound (MD -8.60 points, 95% CI -13.48 to -3.72 points; absolute risk difference 17%, 7% to 26% more). Mean improvement in function with placebo was 3.7 points on a 100-point scale, and 17.8 points with ultrasound (mean difference (MD) 14.10 points, 95% confidence interval (CI) 5.39 to 22.81 points; absolute risk difference 14%, 5% to 23% more). Ninety-one per cent (29/32) of participants reported treatment success with ultrasound compared with 52% (15/29) of participants receiving placebo (risk ratio (RR) 1.75, 95% CI 1.21 to 2.53; absolute risk difference 39%, 18% to 60% more). Mean improvement in quality of life with placebo was 0.40 points on a 10-point scale, and 2.60 points with ultrasound (MD 2.20 points, 95% CI 0.91 points to 3.49 points; absolute risk difference 22%, 9% to 35

  18. Dual ant colony operational modal analysis parameter estimation method

    Science.gov (United States)

    Sitarz, Piotr; Powałka, Bartosz

    2018-01-01

    Operational Modal Analysis (OMA) is a common technique used to examine the dynamic properties of a system. Contrary to experimental modal analysis, the input signal is generated in object ambient environment. Operational modal analysis mainly aims at determining the number of pole pairs and at estimating modal parameters. Many methods are used for parameter identification. Some methods operate in time while others in frequency domain. The former use correlation functions, the latter - spectral density functions. However, while some methods require the user to select poles from a stabilisation diagram, others try to automate the selection process. Dual ant colony operational modal analysis parameter estimation method (DAC-OMA) presents a new approach to the problem, avoiding issues involved in the stabilisation diagram. The presented algorithm is fully automated. It uses deterministic methods to define the interval of estimated parameters, thus reducing the problem to optimisation task which is conducted with dedicated software based on ant colony optimisation algorithm. The combination of deterministic methods restricting parameter intervals and artificial intelligence yields very good results, also for closely spaced modes and significantly varied mode shapes within one measurement point.

  19. Modality and Perceptual-Motor Experience Influence the Detection of Temporal Deviations in Tap Dance Sequences

    Directory of Open Access Journals (Sweden)

    Mauro Murgia

    2017-08-01

    Full Text Available Accurate temporal information processing is critically important in many motor activities within disciplines such as dance, music, and sport. However, it is still unclear how temporal information related to biological motion is processed by expert and non-expert performers. It is well-known that the auditory modality dominates the visual modality in processing temporal information of simple stimuli, and that experts outperform non-experts in biological motion perception. In the present study, we combined these two areas of research; we investigated how experts and non-experts detected temporal deviations in tap dance sequences, in the auditory modality compared to the visual modality. We found that temporal deviations were better detected in the auditory modality compared to the visual modality, and by experts compared to non-experts. However, post hoc analyses indicated that these effects were mainly due to performances obtained by experts in the auditory modality. The results suggest that the experience advantage is not equally distributed across the modalities, and that tap dance experience enhances the effectiveness of the auditory modality but not the visual modality when processing temporal information. The present results and their potential implications are discussed in both temporal information processing and biological motion perception frameworks.

  20. Modality and Perceptual-Motor Experience Influence the Detection of Temporal Deviations in Tap Dance Sequences.

    Science.gov (United States)

    Murgia, Mauro; Prpic, Valter; O, Jenny; McCullagh, Penny; Santoro, Ilaria; Galmonte, Alessandra; Agostini, Tiziano

    2017-01-01

    Accurate temporal information processing is critically important in many motor activities within disciplines such as dance, music, and sport. However, it is still unclear how temporal information related to biological motion is processed by expert and non-expert performers. It is well-known that the auditory modality dominates the visual modality in processing temporal information of simple stimuli, and that experts outperform non-experts in biological motion perception. In the present study, we combined these two areas of research; we investigated how experts and non-experts detected temporal deviations in tap dance sequences, in the auditory modality compared to the visual modality. We found that temporal deviations were better detected in the auditory modality compared to the visual modality, and by experts compared to non-experts. However, post hoc analyses indicated that these effects were mainly due to performances obtained by experts in the auditory modality. The results suggest that the experience advantage is not equally distributed across the modalities, and that tap dance experience enhances the effectiveness of the auditory modality but not the visual modality when processing temporal information. The present results and their potential implications are discussed in both temporal information processing and biological motion perception frameworks.

  1. Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica.

    Science.gov (United States)

    Lokanathan, Yogeswaran; Omar, Norazzila; Ahmad Puzi, Nur Nabilah; Saim, Aminuddin; Hj Idrus, Ruszymah

    2016-01-01

    Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica acts as an antioxidant, reducing the effect of oxidative stress in vitro and in vivo. At the in vitro level, C. asiatica promotes dendrite arborisation and elongation, and also protects the neurons from apoptosis. In vivo studies have shown that the whole extract and also individual compounds of C. asiatica have a protective effect against various neurological diseases. Most of the in vivo studies on neuroprotective effects have focused on Alzheimer's disease, Parkinson's disease, learning and memory enhancement, neurotoxicity and other mental illnesses such as depression and anxiety, and epilepsy. Recent studies have embarked on finding the molecular mechanism of neuroprotection by C. asiatica extract. However, the capability of C. asiatica in enhancing neuroregeneration has not been studied much and is limited to the regeneration of crushed sciatic nerves and protection from neuronal injury in hypoxia conditions. More studies are still needed to identify the compounds and the mechanism of action of C. asiatica that are particularly involved in neuroprotection and neuroregeneration. Furthermore, the extraction method, biochemical profile and dosage information of the C. asiatica extract need to be standardised to enhance the economic value of this traditional herb and to accelerate the entry of C. asiatica extracts into modern medicine.

  2. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    OpenAIRE

    Jung, Jae-Chul; Lee, Yeonju; Moon, Sohyeon; Ryu, Jong Hoon; Oh, Seikwan

    2011-01-01

    The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproectiv...

  3. Neuroprotective function for ramified microglia in hippocampal excitotoxicity

    OpenAIRE

    Vinet, Jonathan; van Weering, Hilmar RJ; Heinrich, Annette; Kälin, Roland E; Wegner, Anja; Brouwer, Nieske; Heppner, Frank L; van Rooijen, Nico; Boddeke, Hendrikus WGM; Biber, Knut

    2012-01-01

    Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excito...

  4. Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica

    OpenAIRE

    Lokanathan, Yogeswaran; Omar, Norazzila; Ahmad Puzi, Nur Nabilah; Saim, Aminuddin; Hj Idrus, Ruszymah

    2016-01-01

    Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica ac...

  5. Evaluation of neuroprotective properties of two synthetic prenylated ...

    African Journals Online (AJOL)

    Results: SX1 and SX2 MNTDs at concentrations of 1850 nM and 105 nM, respectively, did not significantly (p > 0.05) provide neuroprotection against paraquat-induced SH-SY5Y cell death. Only SX2 MNTD and HMNTD significantly (p < 0.05) protected SH-SH5Y cells against 6-OHDA-induced cell death by 10 and 17 ...

  6. Progesterone neuroprotection: The background of clinical trial failure.

    Science.gov (United States)

    Schumacher, Michael; Denier, Christian; Oudinet, Jean-Paul; Adams, David; Guennoun, Rachida

    2016-06-01

    Since the first pioneering studies in the 1990s, a large number of experimental animal studies have demonstrated the neuroprotective efficacy of progesterone for brain disorders, including traumatic brain injury (TBI). In addition, this steroid has major assets: it easily crosses the blood-brain-barrier, rapidly diffuses throughout the brain and exerts multiple beneficial effects by acting on many molecular and cellular targets. Moreover, progesterone therapies are well tolerated. Notably, increased brain levels of progesterone are part of endogenous neuroprotective responses to injury. The hormone thus emerged as a particularly promising protective candidate for TBI and stroke patients. The positive outcomes of small Phase 2 trials aimed at testing the safety and potential protective efficacy of progesterone in TBI patients then provided support and guidance for two large, multicenter, randomized and placebo-controlled Phase 3 trials, with more than 2000 TBI patients enrolled. The negative outcomes of both trials, named ProTECT III and SyNAPSE, came as a big disappointment. If these trials were successful, progesterone would have become the first efficient neuroprotective drug for brain-injured patients. Thus, progesterone has joined the numerous neuroprotective candidates that have failed in clinical trials. The aim of this review is a reappraisal of the preclinical animal studies, which provided the proof of concept for the clinical trials, and we critically examine the design of the clinical studies. We made efforts to present a balanced view of the strengths and limitations of the translational studies and of some serious issues with the clinical trials. We place particular emphasis on the translational value of animal studies and the relevance of TBI biomarkers. The probability of failure of ProTECT III and SyNAPSE was very high, and we present them within the broader context of other unsuccessful trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Stem Cell-Based Neuroprotective and Neurorestorative Strategies

    Directory of Open Access Journals (Sweden)

    Chia-Wei Hung

    2010-05-01

    Full Text Available Stem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke and Parkinson’s disease. Moreover, the potential and possible utilities of induced pluripotent stem cells (iPS, reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases.

  8. Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Hong; Lee, Ik Hwan; Nam, Seung Taek; Hong, Ji; Zhang, Peng [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of); Hwang, Jae Sam [Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-707 (Korea, Republic of); Seok, Heon [Department of Biomedical Engineering, Jungwon University, Goesan, Chungcheongbukdo 367-700 (Korea, Republic of); Choi, Hyemin; Lee, Dong Gun [School of Life Sciences, KNU Creative Bioresearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701 (Korea, Republic of); Kim, Jae Il [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Kim, Ho, E-mail: hokim@daejin.ac.kr [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of)

    2014-06-06

    Highlights: • 11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm. • We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects. • p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. - Abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH{sub 2}-RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson’s disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27{sup Kip1} protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27{sup Kip1} significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27{sup Kip1} degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin.

  9. Curcumin: a potential neuroprotective agent in Parkinson's disease.

    Science.gov (United States)

    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

  10. Neuroprotection and its molecular mechanism following spinal cord injury☆

    Science.gov (United States)

    Liu, Nai-Kui; Xu, Xiao-Ming

    2012-01-01

    Acute spinal cord injury initiates a complex cascade of molecular events termed ‘secondary injury’, which leads to progressive degeneration ranging from early neuronal apoptosis at the lesion site to delayed degeneration of intact white matter tracts, and, ultimately, expansion of the initial injury. These secondary injury processes include, but are not limited to, inflammation, free radical-induced cell death, glutamate excitotoxicity, phospholipase A2 activation, and induction of extrinsic and intrinsic apoptotic pathways, which are important targets in developing neuroprotective strategies for treatment of spinal cord injury. Recently, a number of studies have shown promising results on neuroprotection and recovery of function in rodent models of spinal cord injury using treatments that target secondary injury processes including inflammation, phospholipase A2 activation, and manipulation of the PTEN-Akt/mTOR signaling pathway. The present review outlines our ongoing research on the molecular mechanisms of neuroprotection in experimental spinal cord injury and briefly summarizes our earlier findings on the therapeutic potential of pharmacological treatments in spinal cord injury. PMID:25624837

  11. Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

    International Nuclear Information System (INIS)

    Kim, Dae Hong; Lee, Ik Hwan; Nam, Seung Taek; Hong, Ji; Zhang, Peng; Hwang, Jae Sam; Seok, Heon; Choi, Hyemin; Lee, Dong Gun; Kim, Jae Il; Kim, Ho

    2014-01-01

    Highlights: • 11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm. • We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects. • p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. - Abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH 2 -RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson’s disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27 Kip1 protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27 Kip1 significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27 Kip1 degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin

  12. Molecular Basis for Certain Neuroprotective Effects of Thyroid Hormone

    Directory of Open Access Journals (Sweden)

    Paul eDavis

    2011-10-01

    Full Text Available The pathophysiology of brain damage that is common to ischemia-reperfusion inury and brain trauma includes disordered neuronal and glial cell energetics, intracellular acidosis, calcium toxicity, extracellular excitotoxic glutamate accumulation and dysfunction of the cytoskeleton and endoplasmic reticulum. Thyroid hormone isoforms, 3, 5, 3'-triiodo-L-thyronine (T3 and L-thyroxine (T4, have nongenomic and genomic actions that are relevant to repair of certain features of the pathophysiology of brain damage. Thyroid hormone can nongenomically repair intracullar H+ accumulation by stimulation of the Na+/H+ exchanger and can support desirably low [Ca2+]i.c. by activation of plasma membrane Ca2+-ATPase. Thyroid hormone nongenomically stimulates astrocyte glutamate uptake, an action that protects both glial cells and neurons. The hormone supports the integrity of the cytoskeleton by its effect on actin. Several proteins linked to thyroid hormone action are also neuroprotective. For example, the hormone stimulates expression of the seladin-1 gene whose gene product is anti-apoptotic and is potentially protection in the setting of neurodegeneration. Transthyretin (TTR is a serum transport protein for T4 that is important to blood-brain barrier transfer of the hormone and TTR has also been found to be neuroprotective in the setting of ischemia. Finally, the interesting thyronamine derivatives of T4 have been shown to protect against ischemic brain damage through their ability to induce hypothermia in the intact organism. Thus, thyroid hromone or hormone derivatives have experimental promise as neuroprotective agents.

  13. Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity.

    Science.gov (United States)

    Yang, Le; Yang, Qi; Zhang, Kun; Li, Yu-Jiao; Wu, Yu-Mei; Liu, Shui-Bing; Zheng, Lian-He; Zhao, Ming-Gao

    2014-09-15

    The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca2+ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons.

  14. Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

    Science.gov (United States)

    Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

    2017-06-01

    Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

  15. Progressive ototoxicity after combined modality treatment of medulloblastoma

    International Nuclear Information System (INIS)

    Dutton, S.C.; Neault, M.; Billett, A.E.; LaVally, B.; Scott, R.M.; Sallan, S.E.; Tarbell, N.J.

    1996-01-01

    Objective: Prospective study to evaluate the response rate, survival and toxicity of pre-irradiation chemotherapy in the treatment of children with seeding CNS tumors. Materials and Methods: Forty-two patients with medulloblastoma were enrolled on a prospective pre-irradiation chemotherapy protocol between 1984 and 1990. Patients (Median age 9.5 years; 29 males, 13 females) received post-operative chemotherapy [cisplatinum 100 mg/m2 q 3 weeks) and vincristine (1.5 mg/m2 weekly) for 9 weeks. Infants (4 patients) received nitrogen mustard (6 mg/m2), procarbazine (100 mg/m2) and vincristine (1.5 mg/m2) until age two followed by craniospinal radiation (CSI). Forty-one patients received CSI with ≥ 50 Gy to the posterior fossa (PF). The median doses to the whole brain, PF, and spine were 33.8 Gy, 55.3 Gy, 27.8 Gy, respectively. Results: Five-year overall survival was 86% and event-free survival was 65% (median follow-up for survivors, 61 months). Thirteen of 15 patients with complete surgical resection documented by post-operative imaging remained free of disease during chemotherapy (CT), and were considered unevaluable for response to CT. The response rate (complete plus partial) to pre-irradiation CT was 45% ((13(29))). Ten patients had stable disease and 6 had progressive disease (PD). Three of 6 patients with PD were long-term survivors after CSI. Thirteen patients relapsed with a median time to failure of 14.5 months. Sites of failure were PF (5 pts), spinal cord (3 pts), CNS/meninges (3 pts), PF/spinal cord (1 pt), and bone metastasis (1 pt). Ototoxicity analysis was performed using 24 patients who had normal hearing in the better ear before chemotherapy and at least one follow-up audiogram for comparison after therapy. 17 patients had an audiogram immediately after CT, and 71% of pts ((12(17))) had high frequency hearing impairment beginning in 3000-8000 Hz range. 18% ((3(17))) had hearing loss in the 500-2000 Hz range necessitating a hearing aid post-CT. 22 patients were tested 1-18 months post-CSI, and showed similar hearing profiles compared to post-CT audiograms ((4(22)) pts required hearing aids). 14 patients were tested from 2.5-10 years post-CSI. (11(14)) patients with long-term follow-up audiograms showed progressive hearing loss with more severe deficits compared to the prior audiogram performed between 1-18 months post-CSI. 93% ((13(14))) of these patients had at least high frequency hearing loss. 57% ((8(14))) had deficits requiring a hearing aid. Conclusion: We conclude that pre-irradiation chemotherapy with cisplatinum and vincristine and low dose craniospinal irradiation is effective post-operative therapy for medulloblastoma. However, this regimen is associated with clinically significant hearing loss which is progressive over time. Serial audiograms should be part of routine follow-up care of children with medulloblastoma in order to evaluate and treat the long-term sequelae of successful treatment

  16. Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke

    DEFF Research Database (Denmark)

    Clausen, Bettina Hjelm; Lambertsen, Kate Lykke; Dagnæs-Hansen, Frederik

    2016-01-01

    ), a known neuroprotectant in stroke, can promote neuroprotection, by modulating the detrimental inflammatory response in the tissue at risk. We show by the use of IL-1Ra-overexpressing and IL-1Ra-deficient mice that IL-1Ra is neuroprotective in stroke. Characterization of the cellular and spatiotemporal...... irradiated mice with IL-1Ra-producing bone marrow cells is associated with neuroprotection and recruitment of IL-1Ra-producing leukocytes after stroke. Neuroprotection is also achieved by therapeutic injection of IL-1Ra-producing bone marrow cells 30 min after stroke onset, additionally improving...... by demonstration of IL-1Ra-producing cells in the human cortex early after ischemic stroke. Taken together, our results attribute distinct neuroprotective or neurotoxic functions to segregated subsets of microglia and suggest that treatment strategies increasing the production of IL-1Ra by infiltrating leukocytes...

  17. Graphical representation of covariant-contravariant modal formulae

    Directory of Open Access Journals (Sweden)

    Miguel Palomino

    2011-08-01

    Full Text Available Covariant-contravariant simulation is a combination of standard (covariant simulation, its contravariant counterpart and bisimulation. We have previously studied its logical characterization by means of the covariant-contravariant modal logic. Moreover, we have investigated the relationships between this model and that of modal transition systems, where two kinds of transitions (the so-called may and must transitions were combined in order to obtain a simple framework to express a notion of refinement over state-transition models. In a classic paper, Boudol and Larsen established a precise connection between the graphical approach, by means of modal transition systems, and the logical approach, based on Hennessy-Milner logic without negation, to system specification. They obtained a (graphical representation theorem proving that a formula can be represented by a term if, and only if, it is consistent and prime. We show in this paper that the formulae from the covariant-contravariant modal logic that admit a "graphical" representation by means of processes, modulo the covariant-contravariant simulation preorder, are also the consistent and prime ones. In order to obtain the desired graphical representation result, we first restrict ourselves to the case of covariant-contravariant systems without bivariant actions. Bivariant actions can be incorporated later by means of an encoding that splits each bivariant action into its covariant and its contravariant parts.

  18. Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential

    OpenAIRE

    Ilkay Erdogan Orhan

    2012-01-01

    This paper covers the studies relevant to neuroprotective activity of Centella asiatica (L.) Urban, also known as “Gotu Kola.” The plant is native to the Southeast Asia and has been used traditionally as brain tonic in ayurvedic medicine. The neuroprotective effect of C. asiatica has been searched using the key words “Centella, Centella asiatica, gotu kola, Asiatic pennywort, neuroprotection, and memory” through the electronic databases including Sciencedirect, Web of Science, Scopus, Pubmed,...

  19. Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

    Science.gov (United States)

    Bayliss, Jacqueline A.; Lemus, Moyra B.; Stark, Romana; Santos, Vanessa V.; Thompson, Aiysha; Rees, Daniel J.; Galic, Sandra; Elsworth, John D.; Kemp, Bruce E.; Davies, Jeffrey S.

    2016-01-01

    Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. SIGNIFICANCE STATEMENT The neuroprotective mechanisms of calorie restriction (CR) in Parkinson's disease are unknown. Indeed, the difficulty to adhere to CR necessitates an alternative method to recapitulate the neuroprotective benefits of CR while bypassing dietary constraints. Here we show that CR increases plasma ghrelin, which targets substantia nigra dopamine to maintain neuronal survival. Selective deletion on AMPK beta1 and beta2 subunits only in DAT cre-expressing neurons shows that the ghrelin-induced neuroprotection requires activation of AMPK in substantia nigra dopamine neurons. We have discovered ghrelin as a key metabolic signal, and AMPK in dopamine neurons as its target, which links calorie restriction with neuroprotection in Parkinson's disease. Thus, targeting AMPK in dopamine neurons may provide novel neuroprotective benefits in Parkinson's disease. PMID

  20. Computer-Assisted Traffic Engineering Using Assignment, Optimal Signal Setting, and Modal Split

    Science.gov (United States)

    1978-05-01

    Methods of traffic assignment, traffic signal setting, and modal split analysis are combined in a set of computer-assisted traffic engineering programs. The system optimization and user optimization traffic assignments are described. Travel time func...

  1. Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon beta to provide enhanced axon protection in autoimmune neuroinflammation.

    Science.gov (United States)

    Reick, Christiane; Ellrichmann, Gisa; Thöne, Jan; Scannevin, Robert H; Saft, Carsten; Linker, Ralf A; Gold, Ralf

    2014-07-01

    Despite recent advances in development of treatments for multiple sclerosis, there is still an unmet need for more effective and also safe therapies. Based on the modes of action of interferon-beta (IFN-β) and dimethyl fumarate (DMF), we hypothesized that anti-inflammatory and neuroprotective effects may synergize in experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice by immunization with MOG35-55-peptide. Murine IFN-β was injected s.c. every other day at 10.000IU, and DMF was provided at 15mg/kg by oral gavage twice daily. Control mice received PBS injections and were treated by oral gavage with the vehicle methylcellulose. Mice were scored daily by blinded observers and histological, FACS and cytokine studies were performed to further elucidate the underlying mechanism of action. Combination therapy significantly ameliorated EAE disease course in comparison to controls and monotherapy with IFN-β. Histological analyses showed a significant effect on axon preservation with almost twice as much axons present in inflamed lesions as compared to control. Remarkably, the effect on axonal preservation was more pronounced under combination therapy than with both monotherapies. Neither monotherapy nor combination therapy demonstrated modulation of cytokines and frequency of antigen presenting cells. Combination of IFN-β and DMF resulted in greater beneficial effects with improved tissue protection as compared to the respective monotherapies. Further combination studies of these safe therapies in human disease are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Neuroprotection and secondary damage following spinal cord injury: concepts and methods.

    Science.gov (United States)

    Hilton, Brett J; Moulson, Aaron J; Tetzlaff, Wolfram

    2017-06-23

    Neuroprotection refers to the attenuation of pathophysiological processes triggered by acute injury to minimize secondary damage. The development of neuroprotective treatments represents a major goal in the field of spinal cord injury (SCI) research. In this review, we discuss the strengths and limitations of the methodologies employed to assess secondary damage and neuroprotection in preclinical models of traumatic SCI. We also discuss modelling issues and how new tools might be exploited to study secondary damage and neuroprotection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD...... cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro......M. In conclusion, several classical and newer anticonvulsants have neuroprotective properties in an in vitro model that simulates cerebral ischemia....

  4. Atopia & Aesthetics. A Modal Perspective

    Directory of Open Access Journals (Sweden)

    Yves Millet

    2013-01-01

    Full Text Available Living in an era where global exchanges of forms and ideas are the norm raises some questions about the status of artistic practices. To explore these questions, we use Roland Barthes’ notion of atopia and the complementary yet related notion of Neutral on which Barthes commented in his later years. Atopia highlights the fact that rather than viewing current artistic activities as searches for homogenous identity, we need to view them as belonging to plural communities of practices offering modal and qualitative distinctions. We suggest that adopting this perspective sheds light on the capacity of any individual to act creatively within his or her daily life. Before considering this last point, we will explore how adopting an atopic perspective helps to throw light on the relation between aesthetics and politics.

  5. Investigative modalities in infectious keratitis

    Directory of Open Access Journals (Sweden)

    Gupta Noopur

    2008-01-01

    Full Text Available Standard recommended guidelines for diagnosis of infectious keratitis do exist. Based on an extensive Medline literature search, the various investigative modalities available for aiding the diagnosis of microbial keratitis have been reviewed and described briefly. Preferred practice patterns have been outlined and the importance of routine pre-treatment cultures in the primary management of infectious keratitis has been highlighted. Corneal scraping, tear samples and corneal biopsy are few of the specimens needed to carry out the investigative procedures for diagnosis and for initiating therapy in cases of microbial keratitis. In bacterial, fungal and amoebic keratitis, microscopic examination of smears is essential for rapid diagnosis. Potassium hydroxide (KOH wet mount, Gram′s stain and Giemsa stain are widely used and are important for clinicians to start empirical therapy before microbial culture results are available. The usefulness of performing corneal cultures in all cases of suspected infectious keratitis has been well established. In cases of suspected viral keratitis, therapy can be initiated on clinical judgment alone. If a viral culture is needed, scrapings should directly be inoculated into the viral transport media. In vivo confocal microscopy is a useful adjunct to slit lamp bio-microscopy for supplementing diagnosis in most cases and establishing early diagnosis in many cases of non-responding fungal and amoebic keratitis. This is a non-invasive, high resolution technique which allows rapid detection of Acanthamoeba cysts and trophozoites and fungal hyphae in the cornea long before laboratory cultures give conclusive results. Other new modalities for detection of microbial keratitis include molecular diagnostic techniques like polymerase chain reaction, and genetic finger printing by pulsed field gel electrophoresis.

  6. Methods of Modality Transmission within Intercultural Communication

    Directory of Open Access Journals (Sweden)

    Olga Alexandrovna Nikolaeva

    2017-09-01

    Full Text Available The main idea of the research is the specifics of modality expression in English compared with the Russian language. Therefore, this analysis helps us not only to understand the nature of modality, but also the ways of its expression. For this purpose, the study benefits from comparative analysis methodology. The analysis of similarities and differences in the category of modality in English and Russian languages, translation techniques of modal meanings are investigated in the article. The article contributes to the expansion and deepening of modality linguistic concepts. Materials of the article can be useful in practice of teaching English, especially on the practical classes in translation and in further development of theoretical issues of language modality.

  7. Tetrabenazine is neuroprotective in Huntington's disease mice

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    Tang Tie-Shan

    2010-04-01

    Full Text Available Abstract Background Huntington's disease (HD is a neurodegenerative disorder caused by a polyglutamine (polyQ expansion in Huntingtin protein (Htt. PolyQ expansion in Httexp causes selective degeneration of striatal medium spiny neurons (MSN in HD patients. A number of previous studies suggested that dopamine signaling plays an important role in HD pathogenesis. A specific inhibitor of vesicular monoamine transporter (VMAT2 tetrabenazine (TBZ has been recently approved by Food and Drug Administration for treatment of HD patients in the USA. TBZ acts by reducing dopaminergic input to the striatum. Results In previous studies we demonstrated that long-term feeding with TBZ (combined with L-Dopa alleviated the motor deficits and reduced the striatal neuronal loss in the yeast artificial chromosome transgenic mouse model of HD (YAC128 mice. To further investigate a potential beneficial effects of TBZ for HD treatment, we here repeated TBZ evaluation in YAC128 mice starting TBZ treatment at 2 months of age ("early" TBZ group and at 6 months of age ("late" TBZ group. In agreement with our previous studies, we found that both "early" and "late" TBZ treatments alleviated motor deficits and reduced striatal cell loss in YAC128 mice. In addition, we have been able to recapitulate and quantify depression-like symptoms in TBZ-treated mice, reminiscent of common side effects observed in HD patients taking TBZ. Conclusions Our results further support therapeutic value of TBZ for treatment of HD but also highlight the need to develop more specific dopamine antagonists which are less prone to side-effects.

  8. Physical modalities for treating acne and rosacea.

    Science.gov (United States)

    Jalian, H Ray; Levin, Yakir; Wanner, Molly

    2016-06-01

    Physical modalities provide an important adjunct to medical treatment of acne and rosacea. In patients who cannot tolerate or fail medical treatments, physical modalities offer an alternative approach. For cases of acne scarring, phymatous changes of rosacea, and rosacea-associated telangiectasia, physical modalities such as laser and light treatments represent the treatment of choice. We will review the use of laser and light treatments, photodynamic therapy, and other physical modalities such as targeted therapies for the treatment of acne and rosacea. ©2016 Frontline Medical Communications.

  9. Modalities for an Allegorical Conceptual Data Model

    Directory of Open Access Journals (Sweden)

    Bartosz Zieliński

    2014-05-01

    Full Text Available Allegories are enriched categories generalizing a category of sets and binary relations. In this paper, we extend a new, recently-introduced conceptual data model based on allegories by adding support for modal operators and developing a modal interpretation of the model in any allegory satisfying certain additional (but natural axioms. The possibility of using different allegories allows us to transparently use alternative logical frameworks, such as fuzzy relations. Mathematically, our work demonstrates how to enrich with modal operators and to give a many world semantics to an abstract algebraic logic framework. We also give some examples of applications of the modal extension.

  10. Social Networking Sites: An Adjunctive Treatment Modality for Psychological Problems

    OpenAIRE

    Menon, Indu S.; Sharma, Manoj Kumar; Chandra, Prabha S.; Thennarasu, K.

    2014-01-01

    Background: Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Materials and Methods: Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psyc...

  11. A study of exercise modality and physical self-esteem in breast cancer survivors.

    Science.gov (United States)

    Musanti, Rita

    2012-02-01

    This study, theoretically based on the Exercise Self-Esteem Model, EXSEM, examined effects of exercise modality on physical and global self-esteem (PSE, GSE) in breast cancer survivors. The EXSEM posits GSE at the apex with PSE feeding into GSE. PSE has three subdomains: physical condition (PC), attractive body (AB), and physical strength (PS). The goals were to compare the effect of combination modality versus single-modality exercise on PSE and GSE and to explore the relationship between exercise modality and the subdomains of PSE. Survivors were randomly allocated to flexibility (F), aerobic (A), resistance (R), or aerobic plus resistance (AR), 12-wk, individualized, home-based exercise program. Pre/posttesting included submaximal treadmill test, six-repetition maximum chest press and leg press, YMCA bench press, shoulder/hip flexibility, and bioelectric impedance analysis body composition. Esteem measures were the Physical Self-Perception Profile and the Rosenberg Self-Esteem Scale. Forty-two women completed the study (F = 12, A = 10, R = 9, and AR = 11). Fitness improvements congruent with exercise modality were seen in all groups. PSE and GSE outcomes did not reveal a greater effect from the combination modality program, AR, compared with the single-modality programs A and R. The relationships between the single-modality groups and the subdomains of PC, PS, and AB were supported in the R group (PS and AB increased) and were partially supported in the A group (PC, not AB, increased). A single-modality R program significantly improved all domains of PSE, and participation in the A program improved the PC subdomain. The combination exercise program did not enhance PSE greater than the single-modality programs. EXSEM was a useful framework for exploring esteem in breast cancer survivors.

  12. Food, nutrigenomics, and neurodegeneration--neuroprotection by what you eat!

    Science.gov (United States)

    Virmani, Ashraf; Pinto, Luigi; Binienda, Zbigniew; Ali, Syed

    2013-10-01

    Diet in human health is no longer simple nutrition, but in light of recent research, especially nutrigenomics, it is linked via evolution and genetics to cell health status capable of modulating apoptosis, detoxification, and appropriate gene response. Nutritional deficiency and disease especially lack of vitamins and minerals is well known, but more recently, epidemiological studies suggest a role of fruits and vegetables, as well as essential fatty acids and even red wine (French paradox), in protection against disease. In the early 1990s, various research groups started considering the use of antioxidants (e.g., melatonin, resveratrol, green tea, lipoic acid) and metabolic compounds (e.g., nicotinamide, acetyl-L-carnitine, creatine, coenzyme Q10) as possible candidates in neuroprotection. They were of course considered on par with snake oil salesman (women) at the time. The positive actions of nutritional supplements, minerals, and plant extracts in disease prevention are now mainstream and commercial health claims being made are subject to regulation in most countries. Apart from efficacy and finding, the right dosages, the safety, and especially the level of purification and lack of contamination are all issues that are important as their use becomes widespread. From the mechanistic point of view, most of the time these substances replenish the body's deficiency and restore normal function. However, they also exert actions that are not sensu stricto nutritive and could be considered pharmacological especially that, at times, higher intake than recommended (RDA) is needed to see these effects. Free radicals and neuroinflammation processes underlie many neurodegenerative conditions, even Parkinson's disease and Alzheimer's disease. Curcumin, carotenoids, acetyl-L-carnitine, coenzyme Q10, vitamin D, and polyphenols and other nutraceuticals have the potential to target multiple pathways in these conditions. In summary, augmenting neuroprotective pathways using

  13. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue

    Science.gov (United States)

    Rojas, Julio C.; Bruchey, Aleksandra K.; Gonzalez-Lima, F.

    2011-01-01

    This paper provides the first review of the memory-enhancing and neuroprotective metabolic mechanisms of action of methylene blue in vivo. These mechanisms have important implications as a new neurobiological approach to improve normal memory and to treat memory impairment and neurodegeneration associated with mitochondrial dysfunction. Methylene blue’s action is unique because its neurobiological effects are not determined by regular drug-receptor interactions or drug-response paradigms. Methylene blue shows a hormetic dose-response, with opposite effects at low and high doses. At low doses, methylene blue is an electron cycler in the mitochondrial electron transport chain, with unparalleled antioxidant and cell respiration-enhancing properties that affect the function of the nervous system in a versatile manner. A major role of the respiratory enzyme cytochrome oxidase on the memory-enhancing effects of methylene blue is supported by available data. The memory-enhancing effects have been associated with improvement of memory consolidation in a network-specific and use-dependent fashion. In addition, low doses of methylene blue have also been used for neuroprotection against mitochondrial dysfunction in humans and experimental models of disease. The unique auto-oxidizing property of methylene blue and its pleiotropic effects on a number of tissue oxidases explain its potent neuroprotective effects at low doses. The evidence reviewed supports a mechanistic role of low-dose methylene blue as a promising and safe intervention for improving memory and for the treatment of acute and chronic conditions characterized by increased oxidative stress, neurodegeneration and memory impairment. PMID:22067440

  14. Focal ischemia of the brain after neuroprotected carotid artery stenting.

    Science.gov (United States)

    Schlüter, Michael; Tübler, Thilo; Steffens, Johann C; Mathey, Detlef G; Schofer, Joachim

    2003-09-17

    This study sought to assess the incidence of cerebral ischemia in nonselected patients undergoing neuroprotected carotid angioplasty and stenting (CAS) without preceding multiple-vessel diagnostic angiography. Protection devices to prevent distal embolization during CAS are presently under clinical investigation. Diffusion-weighted magnetic resonance imaging (MRI) visualizes recent ischemia of the brain and may aid in assessing the efficacy of protection devices. Elective CAS was performed in 42 consecutive patients (15 female, 27 male; mean age, 67 +/- 9 years) using six different types of cerebral protection systems. All patients underwent MRI of the brain before and after a total of 44 interventions. Placement and retrieval of the devices and stent deployment was achieved in all procedures. New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures. In the latter, one to three foci (maximum area 43.0 mm(2)) were detected in cerebral regions subtended by the ipsilateral carotid artery in eight cases and by the contralateral carotid artery in one case. In the stroke patient, 12 ischemic foci (maximum area 84.5 mm(2)) were exclusively located in the contralateral hemisphere. Follow-up MRI at 4.1 months (median, n = 7) identified residuals of cerebral ischemia only in this patient. Neuroprotected CAS is associated in about 25% of cases with predominantly silent cerebral ischemia. Our findings suggest manipulation of endoluminal equipment in the supraaortic vessels to be a major risk factor for cerebral embolism during neuroprotected CAS.

  15. Ethanol and Cognition: Indirect Effects, Neurotoxicity and Neuroprotection: A Review

    Directory of Open Access Journals (Sweden)

    John C.M. Brust

    2010-04-01

    Full Text Available Ethanol affects cognition in a number of ways. Indirect effects include intoxication, withdrawal, brain trauma, central nervous system infection, hypoglycemia, hepatic failure, and Marchiafava-Bignami disease. Nutritional deficiency can cause pellagra and Wernicke-Korsakoff disorder. Additionally, ethanol is a direct neurotoxin and in sufficient dosage can cause lasting dementia. However, ethanol also has neuroprotectant properties and in low-to-moderate dosage reduces the risk of dementia, including Alzheimer type. In fetuses ethanol is teratogenic, and whether there exists a safe dose during pregnancy is uncertain and controversial.

  16. A New Triterpene from Buddleja lindleyana with Neuroprotective Effect

    Directory of Open Access Journals (Sweden)

    Ya-Shuo Ren

    2017-07-01

    Full Text Available In the phytochemical investigation of Buddleja lindleyana , a new 3-acetyl substituted triterpene, 13, 28-epoxy-23-hydroxy-3β-acetoxy-olean-11-ene (1, together with four same skeleton type known compounds (2-5 were isolated. The structure of 1 was elucidated by means of extensive spectroscopic analysis. Their neuroprotective effect against 1-methyl-4 -phenylpyridinium ion-induced (MPP +-induced neurotoxicity in SH-SY5Y cells were evaluated. The structure activity relationship of compounds 1-5 has been discussed preliminarily.

  17. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    Directory of Open Access Journals (Sweden)

    Sheida Shaafi

    2014-12-01

    Full Text Available Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries.

  18. Multi-modal locomotion: from animal to application

    International Nuclear Information System (INIS)

    Lock, R J; Burgess, S C; Vaidyanathan, R

    2014-01-01

    The majority of robotic vehicles that can be found today are bound to operations within a single media (i.e. land, air or water). This is very rarely the case when considering locomotive capabilities in natural systems. Utility for small robots often reflects the exact same problem domain as small animals, hence providing numerous avenues for biological inspiration. This paper begins to investigate the various modes of locomotion adopted by different genus groups in multiple media as an initial attempt to determine the compromise in ability adopted by the animals when achieving multi-modal locomotion. A review of current biologically inspired multi-modal robots is also presented. The primary aim of this research is to lay the foundation for a generation of vehicles capable of multi-modal locomotion, allowing ambulatory abilities in more than one media, surpassing current capabilities. By identifying and understanding when natural systems use specific locomotion mechanisms, when they opt for disparate mechanisms for each mode of locomotion rather than using a synergized singular mechanism, and how this affects their capability in each medium, similar combinations can be used as inspiration for future multi-modal biologically inspired robotic platforms. (topical review)

  19. Selective Attention and Sensory Modality in Aging: Curses and Blessings

    Directory of Open Access Journals (Sweden)

    Pascal W. M. Van Gerven

    2016-03-01

    Full Text Available The notion that selective attention is compromised in older adults as a result of impaired inhibitory control is well established. Yet it is primarily based on empirical findings covering the visual modality. Auditory and, especially, cross-modal selective attention are remarkably underexposed in the literature on aging. In the past five years, we have attempted to fill these voids by investigating performance of younger and older adults on equivalent tasks covering all four combinations of visual or auditory target, and visual or auditory distractor information. In doing so, we have demonstrated that older adults are especially impaired in auditory selective attention with visual distraction. This pattern of results was not mirrored by the results from our psychophysiological studies, however, in which both enhancement of target processing and suppression of distractor processing appeared to be age equivalent. We currently conclude that (1 age-related differences of selective attention are modality dependent, (2 age-related differences of selective attention are limited, and (3 it remains an open question whether modality-specific age differences in selective attention are due to impaired distractor inhibition, impaired target enhancement, or both. These conclusions put the longstanding inhibitory deficit hypothesis of aging in a new perspective.

  20. Preemptive analgesia I: physiological pathways and pharmacological modalities.

    LENUS (Irish Health Repository)

    Kelly, D J

    2012-02-03

    PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.

  1. Neuroprotection as initial therapy in acute stroke - Third report of an Ad Hoc Consensus Group Meeting

    NARCIS (Netherlands)

    Bogousslavsky, J; De Keyser, J; Diener, HC; Fieschi, C; Hacke, W; Kaste, M; Orgogozo, JM; Pulsinelli, W; Wahlgren, NG

    1998-01-01

    Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the

  2. Neuroprotection in Parkinson's disease: A systematic review of the preclinical data

    NARCIS (Netherlands)

    Douna, H.; Bavelaar, B.M.; Pellikaan, H.; Olivier, B.; Pieters, T.

    2012-01-01

    Aim: This study aimed to systematically review the preclinical data of neuroprotective agents for Parkinson's disease (PD) to support the translation of these compounds. Methods: The study consisted of two phases. In phase I, Pubmed and Scopus were systematically searched for neuroprotective agents

  3. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    Science.gov (United States)

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection. Copyright © 2013. Published by Elsevier B.V.

  4. Novel Neuroprotective Effects of Melanin-Concentrating Hormone in Parkinson's Disease.

    Science.gov (United States)

    Park, Ji-Yeun; Kim, Seung-Nam; Yoo, Junsang; Jang, Jaehwan; Lee, Ahreum; Oh, Ju-Young; Kim, Hongwon; Oh, Seung Tack; Park, Seong-Uk; Kim, Jongpil; Park, Hi-Joon; Jeon, Songhee

    2017-12-01

    Acupuncture has shown the therapeutic effect on various neurodegenerative disorders including Parkinson's disease (PD). While investigating the neuroprotective mechanism of acupuncture, we firstly found the novel function of melanin-concentrating hormone (MCH) as a potent neuroprotective candidate. Here, we explored whether hypothalamic MCH mediates the neuroprotective action of acupuncture. In addition, we aimed at evaluating the neuroprotective effects of MCH and elucidating underlying mechanism in vitro and in vivo PD models. First, we tested whether hypothalamic MCH mediates the neuroprotective effects of acupuncture by challenging MCH-R1 antagonist (i.p.) in mice PD model. We also investigated whether MCH has a beneficial role in dopaminergic neuronal protection in vitro primary midbrain and human neuronal cultures and in vivo MPTP-induced, Pitx3 -/- , and A53T mutant mice PD models. Transcriptomics followed by quantitative PCR and western blot analyses were performed to reveal the neuroprotective mechanism of MCH. We first found that hypothalamic MCH biosynthesis was directly activated by acupuncture treatment and that administration of an MCH-R1 antagonist reverses the neuroprotective effects of acupuncture. A novel finding is that MCH showed a beneficial role in dopaminergic neuron protection via downstream pathways related to neuronal survival. This is the first study to suggest the novel neuroprotective action of MCH as well as the involvement of hypothalamic MCH in the acupuncture effects in PD, which holds great promise for the application of MCH in the therapy of neurodegenerative diseases.

  5. Large proximal ureteral stones: Ideal treatment modality?

    Directory of Open Access Journals (Sweden)

    B Kadyan

    2016-01-01

    Conclusion: Laparoscopic transperitoneal ureterolithotomy is a minimally invasive, safe and effective treatment modality and should be recommended to all patients of impacted large proximal stones, which are not amenable to URS or extracorporeal shock-wave lithotripsy or as a primary modality of choice especially if patient is otherwise candidate for open surgery.

  6. Modal Transition Systems with Weight Intervals

    DEFF Research Database (Denmark)

    Juhl, Line; Larsen, Kim Guldstrand; Srba, Jiri

    2012-01-01

    We propose weighted modal transition systems, an extension to the well-studied specification formalism of modal transition systems that allows to express both required and optional behaviours of their intended implementations. In our extension we decorate each transition with a weight interval...

  7. History of Civil Engineering Modal Analysis

    DEFF Research Database (Denmark)

    Brincker, Rune

    2008-01-01

    techniques are available for civil engineering modal analysis. The testing of civil structures defers from the traditional modal testing in the sense, that very often it is difficult, or sometimes impossible, to artificially excite a large civil engineering structure. Also, many times, even though...

  8. Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential

    Science.gov (United States)

    Orhan, Ilkay Erdogan

    2012-01-01

    This paper covers the studies relevant to neuroprotective activity of Centella asiatica (L.) Urban, also known as “Gotu Kola.” The plant is native to the Southeast Asia and has been used traditionally as brain tonic in ayurvedic medicine. The neuroprotective effect of C. asiatica has been searched using the key words “Centella, Centella asiatica, gotu kola, Asiatic pennywort, neuroprotection, and memory” through the electronic databases including Sciencedirect, Web of Science, Scopus, Pubmed, and Google Scholar. According to the literature survey, C. asiatica (gotu kola) has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition, prevention of amyloid plaque formation in Alzheimer's disease, dopamine neurotoxicity in Parkinson's disease, and decreasing oxidative stress. Therefore, C. asiatica could be suggested to be a desired phytopharmaceutical with neuroprotective effect emerged from traditional medicine. PMID:22666298

  9. Centella asiatica (L. Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential

    Directory of Open Access Journals (Sweden)

    Ilkay Erdogan Orhan

    2012-01-01

    Full Text Available This paper covers the studies relevant to neuroprotective activity of Centella asiatica (L. Urban, also known as “Gotu Kola.” The plant is native to the Southeast Asia and has been used traditionally as brain tonic in ayurvedic medicine. The neuroprotective effect of C. asiatica has been searched using the key words “Centella, Centella asiatica, gotu kola, Asiatic pennywort, neuroprotection, and memory” through the electronic databases including Sciencedirect, Web of Science, Scopus, Pubmed, and Google Scholar. According to the literature survey, C. asiatica (gotu kola has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition, prevention of amyloid plaque formation in Alzheimer’s disease, dopamine neurotoxicity in Parkinson’s disease, and decreasing oxidative stress. Therefore, C. asiatica could be suggested to be a desired phytopharmaceutical with neuroprotective effect emerged from traditional medicine.

  10. Neuroprotective effect of melatonin in experimentally induced hypobaric hypoxia.

    Science.gov (United States)

    Vornicescu, Corina; Boşca, Bianca; Crişan, Doiniţa; Yacoob, Sumaya; Stan, Nora; Filip, Adriana; Şovrea, Alina

    2013-01-01

    Melatonin (MEL) is an endogenous neurohormone with many biological functions, including a powerful antioxidant effect. The aim of the present study was to determine whether MEL protects the brain tissue from the oxidative stress induced by hypobaric hypoxia (HH) in vivo. This study was performed on Wistar rats randomly assigned in four groups, according to the pressure conditions and treatment: Group 1: normoxia and placebo; Group 2: HH and placebo; Group 3: normoxia and MEL; and Group 4: HH and MEL. The following aspects were evaluated: cognitive function (space reference and memory), oxidative stress parameters - serum and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels -, and brain tissue macroscopic and microscopic morphological changes. Exposure to oxidative stress results in cognitive dysfunctions and biochemical alterations: significant increase of MDA and reduction of GSH in both serum and brain tissue. The most important morphological changes were observed in Group 2: increased cellularity, loss of pericellular haloes, shrunken neurons with scanty cytoplasm and hyperchromatic, pyknotic or absent nuclei; reactive gliosis, edema and blood-brain barrier alterations could also be observed in some areas. MEL treatment significantly diminished all these effects. Our results suggest that melatonin is a neuroprotective antioxidant both in normoxia and hypobaric hypoxia that can prevent and counteract the deleterious effects of oxidative stress (neuronal death, reactive astrogliosis, memory impairment and cognitive dysfunctions). Dietary supplements containing melatonin might be useful neuroprotective agents for the therapy of hypoxia-induced consequences.

  11. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  12. Phytoceramide shows neuroprotection and ameliorates scopolamine-induced memory impairment.

    Science.gov (United States)

    Jung, Jae-Chul; Lee, Yeonju; Moon, Sohyeon; Ryu, Jong Hoon; Oh, Seikwan

    2011-10-28

    The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease.

  13. Antivasoconstrictor effect of the neuroprotective agent dexrazoxane in rat aorta.

    Science.gov (United States)

    Vidrio, Horacio; Carrasco, Omar F; Rodríguez, Rodolfo

    2006-12-14

    Dexrazoxane is used clinically to reduce the cardiotoxicity of anthracycline cancer chemotherapeutic agents, acting by an iron-chelating antioxidant mechanism. In a study designed to explore the possible mechanism of the recently described neuroprotective effect of the drug in cerebral ischemia, its influence on vascular reactivity was determined in rat aortic rings. Dexrazoxane was found to be devoid of direct contractile or relaxant activity and to have no influence on responses to acetylcholine or histamine (relaxation), or to angiotensin or serotonin (contraction). In contrast, it decreased contractions to norepinephrine, as evidenced by rightward displacement of the concentration-response curves. The effect was prevented by the removal of the endothelium and by the alpha(2)-adrenoceptor antagonist yohimbine; it was partially antagonized by the endothelium-derived depolarizing factor inhibitor clotrimazole, but was not affected by L-NAME or indomethacin, inhibitors of endothelial nitric oxide and prostacyclin production. The anti-contractile effect did not occur in rings stimulated with the alpha(1)-adrenoceptor agonist phenylephrine. It was concluded that dexrazoxane opposes norepinephrine vascular contraction by enhancing endothelial alpha(2)-adrenoceptor-mediated release of relaxing factor(s). The drug could thus offset the deleterious vasoconstriction elicited by the increased circulating catecholamines present during cerebral ischemia, and by this mechanism produce neuroprotection.

  14. Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix

    Directory of Open Access Journals (Sweden)

    Wenxia Gong

    2016-04-01

    Full Text Available Seven phthalides, including a new dimeric one named tokinolide C (7, were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4 showed cytotoxicity against three cancer cell lines, with IC50 values of 13.82, 6.79, and 7.92 μM, respectively. Tokinolide A (6 and tokinolide C (6 exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4. We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1, Z-butylidenephthalide (3 and tokinolide A (6 exhibited significant neuroprotective effects.

  15. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

    Science.gov (United States)

    Liu, Zhongwu; Chopp, Michael

    2015-01-01

    Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

  16. Neuroprotective effects of yoga practice: age-, experience-, and frequency-dependent plasticity

    Directory of Open Access Journals (Sweden)

    Chantal eVillemure

    2015-05-01

    Full Text Available Yoga combines postures, breathing, and meditation. Despite reported health benefits, yoga’s effects on the brain has received little study. We used magnetic resonance imaging to compare age-related gray matter (GM decline in yogis and controls. We also examined the effect of increasing yoga experience and weekly practice on GM volume and assessed which aspects of weekly practice contributed most to brain size. Controls displayed the well documented age-related global brain GM decline while yogis did not, suggesting that yoga contributes to protect the brain against age-related decline. Years of yoga experience correlated mostly with GM volume differences in the left hemisphere (insula, frontal operculum and orbitofrontal cortex suggesting that yoga tunes the brain towards a parasympatically-driven mode and positive states. The number of hours of weekly practice correlated with GM volume in the primary somatosensory cortex/superior parietal lobule (S1/SPL, precuneus/posterior cingulate cortex (PCC, hippocampus, and primary visual cortex (V1. Commonality analyses indicated that the combination of postures and meditation contributed the most to the size of the hippocampus, precuneus/PCC, and S1/SPL while the combination of meditation and breathing exercises contributed the most to V1 volume. Yoga’s potential neuroprotective effects may provide a neural basis for some of its beneficial effects.

  17. Prophylactic neuroprotection against stroke: low-dose, prolonged treatment with deferoxamine or deferasirox establishes prolonged neuroprotection independent of HIF-1 function

    Science.gov (United States)

    Zhao, Yanxin; Rempe, David A

    2011-01-01

    Prophylactic neuroprotection against stroke could reduce stroke burden in thousands of patients at high risk of stroke, including those with recent transient ischemic attacks (TIAs). Prolyl hydroxylase inhibitors (PHIs), such as deferoxamine (DFO), reduce stroke volume when administered at high doses in the peristroke period, which is largely mediated by the hypoxia-inducible transcription factor (HIF-1). Yet, in vitro experiments suggest that PHIs may also induce neuroprotection independent of HIF-1. In this study, we examine chronic, prophylactic, low-dose treatment with DFO, or another iron chelator deferasirox (DFR), to determine whether they are neuroprotective with this paradigm and mediate their effects through a HIF-1-dependent mechanism. In fact, prophylactic administration of low-dose DFO or DFR significantly reduces stroke volume. Surprisingly, DFO remained neuroprotective in mice haploinsufficient for HIF-1 (HIF-1+/−) and transgenic mice with conditional loss of HIF-1 function in neurons and astrocytes. Similarly, DFR was neuroprotective in HIF-1+/− mice. Neither DFO nor DFR induced expression of HIF-1 targets. Thus, low-dose chronic administration of DFO or DFR induced a prolonged neuroprotective state independent of HIF-1 function. As DFR is an orally administered and well-tolerated medication in clinical use, it has promise for prophylaxis against stroke in patients at high risk of stroke. PMID:21245873

  18. Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Pankratova, Stanislava; Korshunova, Irina

    2016-01-01

    The cytokine erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently....... These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties....

  19. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

    Science.gov (United States)

    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

  20. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors.

    Science.gov (United States)

    Pazos, M Ruth; Mohammed, Nagat; Lafuente, Hector; Santos, Martin; Martínez-Pinilla, Eva; Moreno, Estefania; Valdizan, Elsa; Romero, Julián; Pazos, Angel; Franco, Rafael; Hillard, Cecilia J; Alvarez, Francisco J; Martínez-Orgado, Jose

    2013-08-01

    The mechanisms underlying the neuroprotective effects of cannabidiol (CBD) were studied in vivo using a hypoxic-ischemic (HI) brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minutes after HI, the piglets were treated with vehicle (HV) or 1 mg/kg CBD, alone (HC) or in combination with 1 mg/kg of a CB₂ receptor antagonist (AM630) or a serotonin 5HT(1A) receptor antagonist (WAY100635). HI decreased the number of viable neurons and affected the amplitude-integrated EEG background activity as well as different prognostic proton-magnetic-resonance-spectroscopy (H(±)-MRS)-detectable biomarkers (lactate/N-acetylaspartate and N-acetylaspartate/choline ratios). HI brain damage was also associated with increases in excitotoxicity (increased glutamate/N-acetylaspartate ratio), oxidative stress (decreased glutathione/creatine ratio and increased protein carbonylation) and inflammation (increased brain IL-1 levels). CBD administration after HI prevented all these alterations, although this CBD-mediated neuroprotection was reversed by co-administration of either WAY100635 or AM630, suggesting the involvement of CB₂ and 5HT(1A) receptors. The involvement of CB₂ receptors was not dependent on a CBD-mediated increase in endocannabinoids. Finally, bioluminescence resonance energy transfer studies indicated that CB₂ and 5HT(1A) receptors may form heteromers in living HEK-293T cells. In conclusion, our findings demonstrate that CBD exerts robust neuroprotective effects in vivo in HI piglets, modulating excitotoxicity, oxidative stress and inflammation, and that both CB₂ and 5HT(1A) receptors are implicated in these effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina.

    Science.gov (United States)

    Macaluso, Claudio; Frishman, Laura J; Frueh, Beatrice; Kaelin-Lang, Alain; Onoe, Shoken; Niemeyer, Günter

    2003-01-01

    It has been postulated that the major physiological role of adenosine is protection of the central nervous system in conditions such as ischemia, hypoxia, or prolonged neuronal excitation. Under these conditions adenosine is released, and exerts multiple effects, including vasodilation, inhibition of neuronal activity, and enhancement of glycogenolysis, resulting in neuroprotection. In this article, published as well as unpublished data on the multiple effects of exogenous adenosine and application of adenosine-related agents, performed using the arterially perfused cat eye, will be reviewed and discussed within the framework of the neuroprotective role of adenosine. The isolated, arterially perfused eye preparation has the advantage of combining integrity of the eye structure, exact control of arterial concentration and timing of applied pharmacological agents, and access to electrophysiological parameters of both retina and optic nerve, as well as the ability to control and monitor perfusate flow. The absence of red blood cells in the perfusate prevents adenosine from being metabolized prior to reaching the eye.

  2. Determination of rolling tyre modal parameters using Finite Element techniques and Operational Modal Analysis

    Science.gov (United States)

    Palanivelu, Sakthivel; Narasimha Rao, K. V.; Ramarathnam, Krishna Kumar

    2015-12-01

    In order to address various noise generation mechanisms and noise propagation phenomena of a tyre, it is necessary to study the tyre dynamic behaviour in terms of modal parameters. This paper enumerates a novel method of finding the modal parameters of a rolling tyre using an Explicit Finite Element Analysis and Operational Modal Analysis (OMA). ABAQUS Explicit, a commercial Finite Element (FE) software code has been used to simulate the experiment, a tyre rolling over a semi-circular straight and inclined cleat. The acceleration responses obtained from these simulations are used as input to the OMA. LMS test lab has been used for carrying out the Operational Modal Analysis. The modal results are compared with the published results of Kindt [22] and validated. Also, the modal results obtained from OMA are compared with FE modal results of stationary unloaded tyre, stationary loaded tyre and Steady State Transport rolling tyre.

  3. Social networking sites: an adjunctive treatment modality for psychological problems.

    Science.gov (United States)

    Menon, Indu S; Sharma, Manoj Kumar; Chandra, Prabha S; Thennarasu, K

    2014-07-01

    Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. It has implications for developing social networking based adjunctive treatment modality for psychological problems.

  4. Conceptual structure within and between modalities

    Directory of Open Access Journals (Sweden)

    Katia eDilkina

    2013-01-01

    Full Text Available Current views of semantic memory share the assumption that conceptual representations are based on multi-modal experience, which activates distinct modality-specific brain regions. This proposition is widely accepted, yet little is known about how each modality contributes to conceptual knowledge and how the structure of this contribution varies across these multiple information sources. We used verbal feature lists, features from drawings and verbal co-occurrence statistics from latent semantic analysis to examine the informational structure in four domains of knowledge: perceptual, functional, encyclopedic and verbal. The goals of the analysis were three-fold: (1 to assess the structure within individual modalities; (2 to compare structures between modalities; and (3 to assess the degree to which concepts organize categorically or randomly.Our results indicated significant and unique structure in all four modalities: perceptually, concepts organize based on prominent features such as shape, size, color and parts; functionally, they group based on use and interaction; encyclopedically, they arrange based on commonality in location or behavior; and verbally, they group associatively or relationally. Visual/perceptual knowledge gives rise to the strongest hierarchical organization and is closest to classic taxonomic structure. Information is organized somewhat similarly in the perceptual and encyclopedic domains, which differs significantly from the structure in the functional and verbal domains. Notably, the verbal modality has the most unique organization, which is not at all categorical but also not random. The idiosyncrasy and complexity of conceptual structure across modalities begs the question of how all of these modality-specific experiences are fused together into coherent, multi-faceted yet unified concepts. Accordingly, both methodological and theoretical implications of the present findings are discussed.

  5. Melatonin–sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a ‘drug–prodrug’ mechanism of action

    Science.gov (United States)

    Egea, Javier; Buendia, Izaskun; Parada, Esther; Navarro, Elisa; Rada, Patricia; Cuadrado, Antonio; López, Manuela G; García, Antonio G; León, Rafael

    2015-01-01

    Background and Purpose Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties. Experimental Approach Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug–prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia. Key Results ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2–antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production. Conclusion and Implications ITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases. PMID:25425158

  6. Modality-Invariant Image Classification Based on Modality Uniqueness and Dictionary Learning.

    Science.gov (United States)

    Kim, Seungryong; Cai, Rui; Park, Kihong; Kim, Sunok; Sohn, Kwanghoon

    2016-12-02

    We present a unified framework for image classification of image sets taken under varying modality conditions. Our method is motivated by a key observation that the image feature distribution is simultaneously influenced by the semantic-class and the modality category label, which limits the performance of conventional methods for that task. With this insight, we introduce modality uniqueness as a discriminative weight that divides each modality cluster from all other clusters. By leveraging the modality uniqueness, our framework is formulated as unsupervised modality clustering and classifier learning based on modality-invariant similarity kernel. Specifically, in the assignment step, each training image is first assigned to the most similar cluster according to its modality. In the update step, based on the current cluster hypothesis, the modality uniqueness and the sparse dictionary are updated. These two steps are formulated in an iterative manner. Based on the final clusters, a modalityinvariant marginalized kernel is then computed, where the similarities between the reconstructed features of each modality are aggregated across all clusters. Our framework enables the reliable inference of semantic-class category for an image, even across large photometric variations. Experimental results show that our method outperforms conventional methods on various benchmarks, such as landmark identification under severely varying weather conditions, domain-adapting image classification, and RGB and near-infrared (NIR) image classification.

  7. Neuroprotective Herbs and Foods from Different Traditional Medicines and Diets

    Directory of Open Access Journals (Sweden)

    Marcello Iriti

    2010-05-01

    Full Text Available Plant secondary metabolites include an array of bioactive constituents form both medicinal and food plants able to improve human health. The exposure to these phytochemicals, including phenylpropanoids, isoprenoids and alkaloids, through correct dietary habits, may promote health benefits, protecting against the chronic degenerative disorders mainly seen in Western industrialized countries, such as cancer, cardiovascular and neurodegenerative diseases. In this review, we briefly deal with some plant foods and herbs of traditional medicines and diets, focusing on their neuroprotective active components. Because oxidative stress and neuroinflammation resulting from neuroglial activation, at the level of neurons, microglial cells and astrocytes, are key factors in the etiopathogenesis of both neurodegenerative and neurological diseases, emphasis will be placed on the antioxidant and anti-inflammatory activity exerted by specific molecules present in food plants or in remedies prescribed by herbal medicines.

  8. Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Ryoma Morigaki

    2017-06-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ in the huntingtin (Htt protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.

  9. Neuroprotective properties of nitric oxide and S-nitrosoglutathione

    International Nuclear Information System (INIS)

    Rauhala, Pekka; Andoh, Tsugunobu; Chiueh, C.C.

    2005-01-01

    Oxidative stress and apoptosis may play an important role in the neurodegeneration. The present paper outlines antioxidative and antiapototic mechanisms of nitric oxide and S-nitrosothiols, which could mediate neuroprotection. Nitric oxide generated by nitric oxide synthase or released from an endogenous S-nitrosothiol, S-nitrosoglutathione may up-regulate antioxidative thioredoxin system and antiapototic Bcl-2 protein through a cGMP-dependent mechanism. Moreover, nitric oxide radicals have been shown to have direct antioxidant effect through their reaction with free radicals and iron-oxygen complexes. In addition to serving as a stabilizer and carrier of nitric oxide, S-nitrosoglutathione may have protective effect through transnitrosylation reactions. Based on these new findings, a hypothesis arises that the homeostasis of nitric oxide, S-nitrosothiols, glutathione, and thioredoxin systems is important for protection against oxidative stress, apoptosis, and related neurodegenerative disorders

  10. Gene expression analysis to identify molecular correlates of pre- and post-conditioning derived neuroprotection.

    Science.gov (United States)

    Prasad, Shiv S; Russell, Marsha; Nowakowska, Margeryta; Williams, Andrew; Yauk, Carole

    2012-06-01

    Mild ischaemic exposures before or after severe injurious ischaemia that elicit neuroprotective responses are referred to as preconditioning and post-conditioning. The corresponding molecular mechanisms of neuroprotection are not completely understood. Identification of the genes and associated pathways of corresponding neuroprotection would provide insight into neuronal survival, potential therapeutic approaches and assessments of therapies for stroke. The objectives of this study were to use global gene expression approach to infer the molecular mechanisms in pre- and post-conditioning-derived neuroprotection in cortical neurons following oxygen and glucose deprivation (OGD) in vitro and then to apply these findings to predict corresponding functional pathways. To this end, microarray analysis was applied to rat cortical neurons with or without the pre- and post-conditioning treatments at 3-h post-reperfusion, and differentially expressed transcripts were subjected to statistical, hierarchical clustering and pathway analyses. The expression patterns of 3,431 genes altered under all conditions of ischaemia (with and without pre- or post-conditioning). We identified 1,595 genes that were commonly regulated within both the pre- and post-conditioning treatments. Cluster analysis revealed that transcription profiles clustered tightly within controls, non-conditioned OGD and neuroprotected groups. Two clusters defining neuroprotective conditions associated with up- and downregulated genes were evident. The five most upregulated genes within the neuroprotective clusters were Tagln, Nes, Ptrf, Vim and Adamts9, and the five most downregulated genes were Slc7a3, Bex1, Brunol4, Nrxn3 and Cpne4. Pathway analysis revealed that the intracellular and second messenger signalling pathways in addition to cell death were predominantly associated with downregulated pre- and post-conditioning associated genes, suggesting that modulation of cell death and signal transduction pathways

  11. Sensor Placement for Modal Parameter Subset Estimation

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Bernal, Dionisio; Damkilde, Lars

    2016-01-01

    ). It is shown that the widely used Effective Independence (EI) method, which uses the modal amplitudes as surrogates for the parameters of interest, provides sensor configurations yielding theoretical lower bound variances whose maxima are up to 30 % larger than those obtained by use of the max-min approach.......The present paper proposes an approach for deciding on sensor placements in the context of modal parameter estimation from vibration measurements. The approach is based on placing sensors, of which the amount is determined a priori, such that the minimum Fisher information that the frequency...... responses carry on the selected modal parameter subset is, in some sense, maximized. The approach is validated in the context of a simple 10-DOF mass-spring-damper system by computing the variance of a set of identified modal parameters in a Monte Carlo setting for a set of sensor configurations, whose...

  12. Modal testing of hydraulic pipeline systems

    Science.gov (United States)

    Mikota, Gudrun; Manhartsgruber, Bernhard; Kogler, Helmut; Hammerle, Franz

    2017-11-01

    Dynamic models of fluid power systems require accurate descriptions of hydraulic pipeline systems. For laminar flow in a rigid pipeline, modal approximations of transcendental transfer functions lead to a multi-degrees-of-freedom description. This suggests the application of experimental modal analysis to investigate fluid dynamics in hydraulic pipeline systems. The concept of modal testing is adapted accordingly and demonstrated for a straight pipeline, the same pipeline with a single side branch, and a pipeline system with three side branches. Frequency response functions are determined by injecting a defined flow rate excitation and measuring pressure responses along the pipelines. The underlying theory is confirmed by comparisons between calculated transcendental, measured, and estimated rational frequency response functions. Natural frequencies, damping ratios, and pressure mode shapes are identified. Although the experiments are made for low flow rates and stiff pipeline walls, they indicate the way to perform modal testing in practical applications of fluid power.

  13. Comparing location memory for 4 sensory modalities.

    Science.gov (United States)

    Schifferstein, Hendrik N J; Smeets, Monique A M; Postma, Albert

    2010-02-01

    Stimuli from all sensory modalities can be linked to places and thus might serve as navigation cues. We compared performance for 4 sensory modalities in a location memory task: Black-and-white drawings of free forms (vision), 1-s manipulated environmental sounds (audition), surface textures of natural and artificial materials (touch), and unfamiliar smells (olfaction) were presented in 10 cubes. In the learning stage, participants walked to a cube, opened it, and perceived its content. Subsequently, in a relocation task, they placed each stimulus back in its original location. Although the proportion of correct locations selected just failed to yield significant differences between the modalities, the proportion of stimuli placed in the vicinity of the correct location or on the correct side of the room was significantly higher for vision than for touch, olfaction, and audition. These outcomes suggest that approximate location memory is superior for vision compared with other sensory modalities.

  14. Representation learning for cross-modality classification

    NARCIS (Netherlands)

    G. van Tulder (Gijs); M. de Bruijne (Marleen)

    2017-01-01

    textabstractDifferences in scanning parameters or modalities can complicate image analysis based on supervised classification. This paper presents two representation learning approaches, based on autoencoders, that address this problem by learning representations that are similar across domains.

  15. Disentangling Linguistic Modality Effects in Semantic Processing.

    Science.gov (United States)

    Moita, Mara; Nunes, Maria Vânia

    2017-04-01

    Sensory systems are essential for perceiving and conceptualizing our semantic knowledge about the world and the way we interact with it. Despite studies reporting neural changes to compensate for the absence of a given sensory modality, studies focusing on the assessment of semantic processing reveal poor performances by deaf individuals when compared with hearing individuals. However, the majority of those studies were not performed in the linguistic modality considered the most adequate to their sensory capabilities (i.e., sign language). Therefore, this exploratory study was developed focusing on linguistic modality effects during semantic retrieval in deaf individuals in comparison with their hearing peers through a category fluency task. Results show a difference in performance between the two linguistic modalities by deaf individuals as well as in the type of linguistic clusters most chosen by participants, suggesting a complex clustering tendency by deaf individuals.

  16. Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants

    Science.gov (United States)

    Hampson, A. J.; Grimaldi, M.; Axelrod, J.; Wink, D.

    1998-01-01

    The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (−)Δ9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-d-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-d-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or α-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia. PMID:9653176

  17. Neuroprotective copper bis(thiosemicarbazonato complexes promote neurite elongation.

    Directory of Open Access Journals (Sweden)

    Laura Bica

    Full Text Available Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD, Parkinson's disease (PD, and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato-copper complex, Cu(II(gtsm on neuritogenesis and neurite elongation (neurogenerative outcomes in PC12 neuronal-related cultures. We found that Cu(II(gtsm induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato complex, Cu(II(atsm, but at a higher concentration. Induction of neurite elongation by Cu(II(gtsm was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II(gtsm treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II(gtsm inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor resulted in analogous elongation of neurites compared to 50 nM Cu(II(gtsm, suggesting a potential link between Cu(II(gtsm-mediated phosphatase inhibition and neurogenerative outcomes.

  18. Neuroprotective effects of DHA in Alzheimer’s disease models

    Directory of Open Access Journals (Sweden)

    Florent-Béchard Sabrina

    2007-05-01

    Full Text Available Alzheimer’s disease (AD is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3 in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i regulation of the expression of potentially protective genes, (ii activation of antiinflammatory pathways, (iii modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases.

  19. Mitochondrial respiration as a target for neuroprotection and cognitive enhancement.

    Science.gov (United States)

    Gonzalez-Lima, F; Barksdale, Bryan R; Rojas, Julio C

    2014-04-15

    This paper focuses on brain mitochondrial respiration as a therapeutic target for neuroprotection and cognitive enhancement. We propose that improving brain mitochondrial respiration is an important future direction in research and treatment of Alzheimer's disease (AD) and other conditions associated with cognitive impairment and neurodegeneration. The central thesis is that supporting and improving brain mitochondrial respiration constitutes a promising neurotherapeutic principle, with potential applications in AD as well as in a wide variety of neuropsychological conditions. We propose three different interventional approaches to improve brain mitochondrial respiration based on (a) pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide detailed examples for each type of intervention. First, low-dose USP methylene blue is described as a pharmacological intervention that can successfully increase mitochondrial respiration and result in memory enhancement and neuroprotection. Second, transcranial low-level light/laser therapy with near-infrared light is used to illustrate a photobiomodulation intervention with similar neurometabolic mechanisms of action as low-dose methylene blue. Finally, a nutrition intervention to improve mitochondrial respiration is proposed by increasing ketone bodies in the diet. The evidence discussed for each intervention supports a fundamental neurotherapeutic strategy based on improving oxidative energy metabolism while at the same time reducing the pro-oxidant tendencies of the nervous system. Targeting brain mitochondrial respiration with these three types of interventions is proposed as part of a holistic neurotherapeutic approach to improve brain energy metabolism and antioxidant defenses. This strategy represents a promising new bioenergetics direction for treatment of AD and other neuropsychological disorders featuring cognitive impairment and neurodegeneration. Copyright © 2013 Elsevier Inc. All rights

  20. DICOM versus HL7 for modality interfacing

    OpenAIRE

    Oosterwijk, Herman

    1998-01-01

    Digital modalities such as CT, MRI, Ultrasound and Computerized Radiography systems, generating softcopy images to be used by a Picture Archiving and Communication System (PACS), need to identify the images properly in order to retrieve and manage them. In many cases, a technologist re-enters patient demographic and study related information at the modality, even although it is usually already present somewhere in the hospital Information System (IS). In order to achieve a higher level of eff...

  1. Neuroprotection without immunomodulation is not sufficient to reduce first relapse severity in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Johansen, Flemming Fryd

    2010-01-01

    OBJECTIVES: Multiple sclerosis can be characterized by a strong neuroinflammatory and progressive neurodegenerative component leading to prolonged disability. The synthetic compound R(+)WIN55,212-2 is reported to be neuroprotective at moderate doses and both neuroprotective and immunomodulatory...... at high doses, most likely due to differences in receptor affinities. In order to investigate the effects of neuroprotection and immunomodulation in an animal model of multiple sclerosis, we examined the impact of increasing concentrations of R(+)WIN55,212-2 on the inflammatory profile in CNS during first...

  2. Eigenvectors phase correction in inverse modal problem

    Science.gov (United States)

    Qiao, Guandong; Rahmatalla, Salam

    2017-12-01

    The solution of the inverse modal problem for the spatial parameters of mechanical and structural systems is heavily dependent on the quality of the modal parameters obtained from the experiments. While experimental and environmental noises will always exist during modal testing, the resulting modal parameters are expected to be corrupted with different levels of noise. A novel methodology is presented in this work to mitigate the errors in the eigenvectors when solving the inverse modal problem for the spatial parameters. The phases of the eigenvector component were utilized as design variables within an optimization problem that minimizes the difference between the calculated and experimental transfer functions. The equation of motion in terms of the modal and spatial parameters was used as a constraint in the optimization problem. Constraints that reserve the positive and semi-positive definiteness and the inter-connectivity of the spatial matrices were implemented using semi-definite programming. Numerical examples utilizing noisy eigenvectors with augmented Gaussian white noise of 1%, 5%, and 10% were used to demonstrate the efficacy of the proposed method. The results showed that the proposed method is superior when compared with a known method in the literature.

  3. Modal analysis using a Fourier analyzer, curve-fitting, and modal tuning

    Science.gov (United States)

    Craig, R. R., Jr.; Chung, Y. T.

    1981-01-01

    The proposed modal test program differs from single-input methods in that preliminary data may be acquired using multiple inputs, and modal tuning procedures may be employed to define closely spaced frquency modes more accurately or to make use of frequency response functions (FRF's) which are based on several input locations. In some respects the proposed modal test proram resembles earlier sine-sweep and sine-dwell testing in that broadband FRF's are acquired using several input locations, and tuning is employed to refine the modal parameter estimates. The major tasks performed in the proposed modal test program are outlined. Data acquisition and FFT processing, curve fitting, and modal tuning phases are described and examples are given to illustrate and evaluate them.

  4. Mixed-Modality Stimulation to Evoke Two Modalities Simultaneously in One Channel for Electrocutaneous Sensory Feedback.

    Science.gov (United States)

    Choi, Kyunghwan; Kim, Pyungkang; Kim, Kyung-Soo; Kim, Soohyun

    2017-12-01

    One of the long-standing challenges in upper limb prosthetics is restoring the sensory feedback that is missing due to amputation. Two approaches have previously been presented to provide various types of sensory information to users, namely, multi-modality sensory feedback and using an array of single-modality stimulators. However, the feedback systems used in these approaches were too bulky to be embedded in prosthesis sockets. In this paper, we propose an electrocutaneous sensory feedback method that is capable of conveying two modalities simultaneously with only one electrode. The stimulation method, which we call mixed-modality stimulation, utilizes the phenomenon in which the superposition of two electric pulse trains of different frequencies is able to evoke two different modalities (i.e., pressure and tapping) at the same time. We conducted psychophysical experiments in which healthy subjects were required to recognize the intensity of pressure or the frequency of tapping from mixed-modality or two-channel stimulations. The results demonstrated that the subjects were able to discriminate the features of the two modalities in one electrode during mixed-modality stimulation and that the accuracies of successful recognitions (mean ± standard deviation) for the two feedback variables were 84.3 ± 7% for mixed-modality stimulation and 89.5 ± 6% for two-channel dual-modality stimulation, showing no statistically significant difference. Therefore, mixed-modality stimulation is an attractive method for modulating two modalities independently with only one electrode, and it could be used for implementing a compact sensory feedback system that is able to provide two different types of sensory information from prosthetics.

  5. Metaphysical Modality, Modality of Predicate and the Theory of "Decisive Necessity”

    Directory of Open Access Journals (Sweden)

    L. Nabavi

    2010-01-01

    Full Text Available Aristotle in the Organon (1949: 9,30 a ,15-19 explicitly states that in a categorical syllogism when the minor premise is absolute (without modality operator and the major is necessary, the conclusion will be necessary too. This Aristotle's view has been the source of many conflicts and disputes in the history of logic. The famous logicians and historians of logic in the twentieth century as "Nicholas Rescher" and "Becker" believe that Aristotle's view is justifiable and defensible (at least compared to the first figure only if, the modality of major premise is considered as the property of predicate (modality de re. Today, we know very well that the modality of predicate is closely linked to Metaphysical and philosophical Modality. “Shihab al-Din al- Suhrawardi” in the theory of "Decisive (Battateh Necessity” by accepting this base, explicitly states that, in the beginning, the modality must be mentioned as a part of the predicate and then the modality of relation or copula is summarized and reduced to necessity. The modern formalization of the most important part of this theory is as follows: ("x (àAx É à Bx º ("x □ (àAx É à BxThis paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  6. Modal Parameters from a Wind Turbine Wing by Operational Modal Analysis

    DEFF Research Database (Denmark)

    Herlufsen, H.; Møller, N.; Brincker, Rune

    2002-01-01

    Operational Modal Analysis also known as Ambient Modal Analysis has an increasing interest in mechanical engineering. Especially on big structures where the excitation and not less important the determination of the forces is most often a problem. In a structure like a wind turbine wing where...... the modes occur both close in frequency and bidirectional the Ambient excitation has big advantages. In this paper modal parameters are identified from the wing by operational modal analysis. For the parameter identification both parametric and non-parametric techniques are used. Advantages...

  7. Large Margin Multi-Modal Multi-Task Feature Extraction for Image Classification.

    Science.gov (United States)

    Yong Luo; Yonggang Wen; Dacheng Tao; Jie Gui; Chao Xu

    2016-01-01

    The features used in many image analysis-based applications are frequently of very high dimension. Feature extraction offers several advantages in high-dimensional cases, and many recent studies have used multi-task feature extraction approaches, which often outperform single-task feature extraction approaches. However, most of these methods are limited in that they only consider data represented by a single type of feature, even though features usually represent images from multiple modalities. We, therefore, propose a novel large margin multi-modal multi-task feature extraction (LM3FE) framework for handling multi-modal features for image classification. In particular, LM3FE simultaneously learns the feature extraction matrix for each modality and the modality combination coefficients. In this way, LM3FE not only handles correlated and noisy features, but also utilizes the complementarity of different modalities to further help reduce feature redundancy in each modality. The large margin principle employed also helps to extract strongly predictive features, so that they are more suitable for prediction (e.g., classification). An alternating algorithm is developed for problem optimization, and each subproblem can be efficiently solved. Experiments on two challenging real-world image data sets demonstrate the effectiveness and superiority of the proposed method.

  8. Working memory resources are shared across sensory modalities.

    Science.gov (United States)

    Salmela, V R; Moisala, M; Alho, K

    2014-10-01

    A common assumption in the working memory literature is that the visual and auditory modalities have separate and independent memory stores. Recent evidence on visual working memory has suggested that resources are shared between representations, and that the precision of representations sets the limit for memory performance. We tested whether memory resources are also shared across sensory modalities. Memory precision for two visual (spatial frequency and orientation) and two auditory (pitch and tone duration) features was measured separately for each feature and for all possible feature combinations. Thus, only the memory load was varied, from one to four features, while keeping the stimuli similar. In Experiment 1, two gratings and two tones-both containing two varying features-were presented simultaneously. In Experiment 2, two gratings and two tones-each containing only one varying feature-were presented sequentially. The memory precision (delayed discrimination threshold) for a single feature was close to the perceptual threshold. However, as the number of features to be remembered was increased, the discrimination thresholds increased more than twofold. Importantly, the decrease in memory precision did not depend on the modality of the other feature(s), or on whether the features were in the same or in separate objects. Hence, simultaneously storing one visual and one auditory feature had an effect on memory precision equal to those of simultaneously storing two visual or two auditory features. The results show that working memory is limited by the precision of the stored representations, and that working memory can be described as a resource pool that is shared across modalities.

  9. Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

    DEFF Research Database (Denmark)

    Erbayraktar, Serhat; Grasso, Giovanni; Sfacteria, Alessandra

    2003-01-01

    (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation...... of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did...... importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection....

  10. ACh receptors link two signaling pathways to neuroprotection against glutamate-induced excitotoxicity in isolated RGCs.

    Science.gov (United States)

    Asomugha, Chinwe O; Linn, David M; Linn, Cindy L

    2010-01-01

    Previous studies have reported that activation of nicotinic acetylcholine (ACh) receptors (nAChRs) on cultured pig retinal ganglion cells (RGCs) has a neuroprotective effect against glutamate-induced excitotoxicity. However, the mechanism linking nAChRs to neuroprotection is unknown. Here, we tested the hypothesis that signaling cascades involving p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) --> Akt are involved in linking activation of nAChRs to neuroprotection in isolated pig RGCs. In ELISA studies, regulation of phosphorylated p38 MAPK and Akt were analyzed after inducing excitotoxicity or neuroprotection in the presence and absence of specific inhibitors for p38 MAPK and PI3K. ELISA results demonstrated that ACh significantly increased phosphorylated Akt and decreased p38 MAPK. Glutamate increased phosphorylated p38 MAPK but had no significant effect on phosphorylated Akt. Other ELISA studies using p38 MAPK and PI3K inhibitors also supported the hypothesis that ACh up-regulated Bcl-2 levels downstream from PI3K and Akt, whereas glutamate down-regulated Bcl-2 levels downstream from p38 MAPK. RGC survival was subsequently assessed by culturing RGCs in conditions to induce excitotoxicity or neuroprotection in the presence or absence of specific inhibitors of p38 MAPK or PI3K. The p38 MAPK inhibitor significantly decreased the number of RGCs that died by glutamate-induced excitotoxicity but had no effect on the number of cells that survived because of ACh-induced neuroprotection. PI3K inhibitors significantly decreased cell survival caused by ACh-induced neuroprotection but had no effect on cell death caused by glutamate-induced excitotoxicity. These results demonstrate that glutamate mediates excitotoxicity through the p38 MAPK signaling pathway and that ACh provides neuroprotection by stimulating the PI3K --> Akt --> Bcl-2 signaling pathway and inhibiting the p38 MAPK --> Bcl-2 pathway.

  11. Multilayer modal actuator-based piezoelectric transformers.

    Science.gov (United States)

    Huang, Yao-Tien; Wu, Wen-Jong; Wang, Yen-Chieh; Lee, Chih-Kung

    2007-02-01

    An innovative, multilayer piezoelectric transformer equipped with a full modal filtering input electrode is reported herein. This modal-shaped electrode, based on the orthogonal property of structural vibration modes, is characterized by full modal filtering to ensure that only the desired vibration mode is excited during operation. The newly developed piezoelectric transformer is comprised of three layers: a multilayered input layer, an insulation layer, and a single output layer. The electrode shape of the input layer is derived from its structural vibration modal shape, which takes advantage of the orthogonal property of the vibration modes to achieve a full modal filtering effect. The insulation layer possesses two functions: first, to couple the mechanical vibration energy between the input and output, and second, to provide electrical insulation between the two layers. To meet the two functions, a low temperature, co-fired ceramic (LTCC) was used to provide the high mechanical rigidity and high electrical insulation. It can be shown that this newly developed piezoelectric transformer has the advantage of possessing a more efficient energy transfer and a wider optimal working frequency range when compared to traditional piezoelectric transformers. A multilayer piezoelectric, transformer-based inverter applicable for use in LCD monitors or portable displays is presented as well.

  12. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions.

    Science.gov (United States)

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li

    2014-08-18

    Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

  13. Automated Modal Parameter Estimation for Operational Modal Analysis of Large Systems

    DEFF Research Database (Denmark)

    Andersen, Palle; Brincker, Rune; Goursat, Maurice

    2007-01-01

    In this paper the problems of doing automatic modal parameter extraction and how to account for large number of data to process are considered. Two different approaches for obtaining the modal parameters automatically using OMA are presented: The Frequency Domain Decomposition (FDD) technique...

  14. Cross-modal links among vision, audition, and touch in complex environments.

    Science.gov (United States)

    Ferris, Thomas K; Sarter, Nadine B

    2008-02-01

    This study sought to determine whether performance effects of cross-modal spatial links that were observed in earlier laboratory studies scale to more complex environments and need to be considered in multimodal interface design. It also revisits the unresolved issue of cross-modal cuing asymmetries. Previous laboratory studies employing simple cues, tasks, and/or targets have demonstrated that the efficiency of processing visual, auditory, and tactile stimuli is affected by the modality, lateralization, and timing of surrounding cues. Very few studies have investigated these cross-modal constraints in the context of more complex environments to determine whether they scale and how complexity affects the nature of cross-modal cuing asymmetries. Amicroworld simulation of battlefield operations with a complex task set and meaningful visual, auditory, and tactile stimuli was used to investigate cuing effects for all cross-modal pairings. Significant asymmetric performance effects of cross-modal spatial links were observed. Auditory cues shortened response latencies for collocated visual targets but visual cues did not do the same for collocated auditory targets. Responses to contralateral (rather than ipsilateral) targets were faster for tactually cued auditory targets and each visual-tactile cue-target combination, suggesting an inhibition-of-return effect. The spatial relationships between multimodal cues and targets significantly affect target response times in complex environments. The performance effects of cross-modal links and the observed cross-modal cuing asymmetries need to be examined in more detail and considered in future interface design. The findings from this study have implications for the design of multimodal and adaptive interfaces and for supporting attention management in complex, data-rich domains.

  15. Affirmation Modality in Bulgarian, Macedonian and Serbian

    Directory of Open Access Journals (Sweden)

    Marcin Grygiel

    2015-06-01

    Full Text Available Affirmation Modality in Bulgarian, Macedonian and Serbian In the case of affirmation modality the speakers transform their utterances by stressing or attributing a positive value as an additional component added to the semantic structure of a proposition. This type of affirmative polarization is triggered in opposition to negation or hypothetically negative contexts. The goal of the present paper is twofold: on the one hand to compare and contrast affirmative periphrastic constructions in Bulgarian, Macedonian and Serbian and, on the other hand, to ascertain what these constructions reveal regarding the organization of grammatical categories in general and the status of affirmation modality as a coherent and homogenous category with a linguistic validity.

  16. Nonoperative modalities to treat symptomatic cervical spondylosis.

    LENUS (Irish Health Repository)

    Hirpara, Kieran Michael

    2012-01-01

    Cervical spondylosis is a common and disabling condition. It is generally felt that the initial management should be nonoperative, and these modalities include physiotherapy, analgesia and selective nerve root injections. Surgery should be reserved for moderate to severe myelopathy patients who have failed a period of conservative treatment and patients whose symptoms are not adequately controlled by nonoperative means. A review of the literature supporting various modalities of conservative management is presented, and it is concluded that although effective, nonoperative treatment is labour intensive, requiring regular review and careful selection of medications and physical therapy on a case by case basis.

  17. The Wigner distribution function in modal characterisation

    CSIR Research Space (South Africa)

    Mredlana, Prince

    2016-07-01

    Full Text Available function in modal characterisation P. MREDLANA1, D. NAIDOO1, C MAFUSIRE2, T. KRUGER2, A. DUDLEY1,3, A. FORBES1,3 1CSIR National Laser Centre, PO BOX 395, Pretoria 0001, South Africa. 2Department of Physics, Faculty of Natural and Agricultural... these modal weights is the main aim of the decomposition, the coefficients yield information about the amplitude and phase of the orthogonal modes. Using this, we can reconstruct the entire field. Let 𝑓 𝑥 be a field function in the spatial domain...

  18. Nonoperative Modalities to Treat Symptomatic Cervical Spondylosis

    Directory of Open Access Journals (Sweden)

    Kieran Michael Hirpara

    2012-01-01

    Full Text Available Cervical spondylosis is a common and disabling condition. It is generally felt that the initial management should be nonoperative, and these modalities include physiotherapy, analgesia and selective nerve root injections. Surgery should be reserved for moderate to severe myelopathy patients who have failed a period of conservative treatment and patients whose symptoms are not adequately controlled by nonoperative means. A review of the literature supporting various modalities of conservative management is presented, and it is concluded that although effective, nonoperative treatment is labour intensive, requiring regular review and careful selection of medications and physical therapy on a case by case basis.

  19. The neuroprotective agent CNTF decreases neuronal metabolites in the rat striatum: an in vivo multimodal magnetic resonance imaging study

    Science.gov (United States)

    Carrillo-de Sauvage, Maria-Angeles; Flament, Julien; Bramoulle, Yann; Ben Haim, Lucile; Guillermier, Martine; Berniard, Aurélie; Aurégan, Gwennaëlle; Houitte, Diane; Brouillet, Emmanuel; Bonvento, Gilles; Hantraye, Philippe; Valette, Julien; Escartin, Carole

    2015-01-01

    Ciliary neurotrophic factor (CNTF) is neuroprotective against multiple pathologic conditions including metabolic impairment, but the mechanisms are still unclear. To delineate CNTF effects on brain energy homeostasis, we performed a multimodal imaging study, combining in vivo proton magnetic resonance spectroscopy, high-performance liquid chromatography analysis, and in situ glutamate imaging by chemical exchange saturation transfer. Unexpectedly, we found that CNTF expression through lentiviral gene transfer in the rat striatum significantly decreased the levels of neuronal metabolites (N-acetyl-aspartate, N-acetyl-aspartyl-glutamate, and glutamate). This preclinical study shows that CNTF remodels brain metabolism, and suggests that decreased levels of neuronal metabolites may occur in the absence of neuronal dysfunction. PMID:25833344

  20. Neuroprotective function for ramified microglia in hippocampal excitotoxicity

    Directory of Open Access Journals (Sweden)

    Vinet Jonathan

    2012-01-01

    Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

  1. Rasagiline, Parkinson neuroprotection, and delayed-start trials

    Science.gov (United States)

    Ahlskog, J. Eric; Uitti, Ryan J.

    2010-01-01

    Rasagiline has been studied as a Parkinson disease (PD) neuroprotective agent in 2 major clinical trials, utilizing the delayed-start design in an attempt to separate symptomatic drug benefits from a disease-modifying effect. The ostensibly positive outcomes of these studies, however, are obscured by potential confounding factors that seem intrinsic to this trial design, including 1) very small changes in clinical outcome measures that could easily be overshadowed by other influences; 2) probable incomplete blinding to study end; 3) subjective components of the Unified Parkinson's Disease Rating Scale (UPDRS) scoring system; and 4) practice influences from repeated scoring. Interpretation of the recent Attenuation of Disease Progression with Azilect Given Once-daily (ADAGIO) trials is especially problematic given 1) divergent results with the 2 symptomatically beneficial doses and 2) variability in UPDRS scores with active rasagiline, which was twice the magnitude of the major finding of the study. These studies further illustrate the difficulty in documenting a disease-modifying effect when considering a PD drug with symptomatic benefit. GLOSSARY ADAGIO = Attenuation of Disease Progression with Azilect Given Once-daily trial; PD = Parkinson disease; TEMPO = TVP-1012 in Early Monotherapy for PD Outpatients study; UPDRS = Unified Parkinson's Disease Rating Scale. PMID:20368634

  2. Evaluating a simple method of neuroprotective hypothermia for newborn infants.

    Science.gov (United States)

    Horn, A R; Harrison, M C; Linley, L L

    2010-06-01

    This study describes and evaluates a simple method of neuroprotective hypothermia for infants with hypoxic-ischaemic encephalopathy (HIE). Five term infants with HIE were cooled by applying soft, cold gel bags to the head. A radiant warmer, set to 34 degrees C, servo-controlled the temperature measured at a probe between the infant's back and the mattress. The infants' heads were shielded from the warmer. After 72 h, the infants were re-warmed by 0.2 degrees C per hour, by adjusting the radiant warmer. A rectal temperature of 34 degrees C was attained in a median time of 45 min. Mean rectal temperatures during cooling were 33.9 +/- 0.3 degrees C. There was good correlation between insulated back temperatures and deep rectal temperatures (r = 0.76). There were no major or irreversible adverse events during cooling. This method of cooling achieved rectal temperatures within the target range of 33-34 degrees C and re-warming was effective.

  3. Pridopidine activates neuroprotective pathways impaired in Huntington Disease.

    Science.gov (United States)

    Geva, Michal; Kusko, Rebecca; Soares, Holly; Fowler, Kevin D; Birnberg, Tal; Barash, Steve; -Wagner, Avia Merenlender; Fine, Tania; Lysaght, Andrew; Weiner, Brian; Cha, Yoonjeong; Kolitz, Sarah; Towfic, Fadi; Orbach, Aric; Laufer, Ralph; Zeskind, Ben; Grossman, Iris; Hayden, Michael R

    2016-09-15

    Pridopidine has demonstrated improvement in Huntington Disease (HD) motor symptoms as measured by secondary endpoints in clinical trials. Originally described as a dopamine stabilizer, this mechanism is insufficient to explain the clinical and preclinical effects of pridopidine. This study therefore explored pridopidine's potential mechanisms of action. The effect of pridopidine versus sham treatment on genome-wide expression profiling in the rat striatum was analysed and compared to the pathological expression profile in Q175 knock-in (Q175 KI) vs Q25 WT mouse models. A broad, unbiased pathway analysis was conducted, followed by testing the enrichment of relevant pathways. Pridopidine upregulated the BDNF pathway (P = 1.73E-10), and its effect on BDNF secretion was sigma 1 receptor (S1R) dependent. Many of the same genes were independently found to be downregulated in Q175 KI mice compared to WT (5.2e-7 diseases, including HD, these findings suggest that pridopidine may exert neuroprotective effects beyond its role in alleviating some symptoms of HD. © The Author 2016. Published by Oxford University Press.

  4. Neuroprotective effects of statins against amyloid β-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hsin-Hua Li

    2018-01-01

    Full Text Available A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ levels by affecting amyloid precursor protein (APP cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.

  5. Quercetin, not caffeine, is a major neuroprotective component in coffee.

    Science.gov (United States)

    Lee, Moonhee; McGeer, Edith G; McGeer, Patrick L

    2016-10-01

    Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Antihypertensive and neuroprotective effects of astaxanthin in experimental animals.

    Science.gov (United States)

    Hussein, Ghazi; Nakamura, Masami; Zhao, Qi; Iguchi, Tomomi; Goto, Hirozo; Sankawa, Ushio; Watanabe, Hiroshi

    2005-01-01

    Astaxanthin is a natural antioxidant carotenoid that occurs in a wide variety of living organisms. We investigated, for the first time, antihypertensive effects of astaxanthin (ASX-O) in spontaneously hypertensive rats (SHR). Oral administration of ASX-O for 14 d induced a significant reduction in the arterial blood pressure (BP) in SHR but not in normotensive Wistar Kyoto (WKY) strain. The long-term administration of ASX-O (50 mg/kg) for 5 weeks in stroke prone SHR (SHR-SP) induced a significant reduction in the BP. It also delayed the incidence of stroke in the SHR-SP. To investigate the action mechanism of ASX-O, the effects on PGF(2alpha)-induced contractions of rat aorta treated with NG-nitro-L-arginine methyl ester (L-NAME) were studied in vitro. ASX-O (1 to 10 microM) induced vasorelaxation mediated by nitric oxide (NO). The results suggest that the antihypertensive effect of ASX-O may be due to a NO-related mechanism. ASX-O also showed significant neuroprotective effects in ischemic mice, presumably due to its antioxidant potential. Pretreatment of the mice with ASX-O significantly shortened the latency of escaping onto the platform in the Morris water maze learning performance test. In conclusion, these results indicate that astaxanthin can exert beneficial effects in protection against hypertension and stroke and in improving memory in vascular dementia.

  7. Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats.

    Science.gov (United States)

    Galvão, Rita I M; Diógenes, João P L; Maia, Graziela C L; Filho, Emídio A S; Vasconcelos, Silvânia M M; de Menezes, Dalgimar B; Cunha, Geanne M A; Viana, Glauce S B

    2005-01-01

    In this study we investigated the effects of Tenoxicam, a type 2 cyclooxygenase (COX-2) inhibitor, on brain damage induced by ischemia-reperfusion. Male Wistar rats (18-month old average) were anesthetized and submitted to ischemia occlusion of both common carotid arteries (BCAO) for 45 min. After 24 h of reperfusion, rats were decapitated and hippocampi removed for further assays. Animals were divided into sham-operated, ischemia, ischemia + Tenoxicam 2.5 mg/kg, and ischemia + Tenoxicam 10 mg/kg groups. Tenoxicam was administered intraperitoneally immediately after BCAO. Histological analyses show that ischemia produced significant striatal as well as hippocampal lesions which were reversed by the Tenoxicam treatment. Tenoxicam also significantly reduced, to control levels, the increased myeloperoxidase activity in hippocampus homogenates observed after ischemia. However, nitrite concentrations showed only a tendency to decrease in the ischemia + Tenoxicam groups, as compared to that of ischemia alone. On the other hand, hippocampal glutamate and aspartate levels were not altered by Tenoxicam. In conclusion, we showed that ischemia is certainly related to inflammation and to increased free radical production, and selective COX-2 inhibitors might be neuroprotective agents of potential benefit in the treatment of cerebral brain ischemia.

  8. Neuroprotective effects of phytochemicals on dopaminergic neuron cultures.

    Science.gov (United States)

    Sandoval-Avila, S; Diaz, N F; Gómez-Pinedo, U; Canales-Aguirre, A A; Gutiérrez-Mercado, Y K; Padilla-Camberos, E; Marquez-Aguirre, A L; Díaz-Martínez, N E

    2016-06-21

    Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    Directory of Open Access Journals (Sweden)

    Karimzadeh Fariba

    2012-06-01

    Full Text Available Abstract Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  10. Creatine for neuroprotection in neurodegenerative disease: end of story?

    Science.gov (United States)

    Bender, Andreas; Klopstock, Thomas

    2016-08-01

    Creatine (Cr) is a natural compound that plays an important role in cellular energy homeostasis. In addition, it ameliorates oxidative stress, glutamatergic excitotoxicity, and apoptosis in vitro as well as in vivo. Since these pathomechanisms are implicated to play a role in several neurodegenerative diseases, Cr supplementation as a neuroprotective strategy has received a lot of attention with several positive animal studies in models of Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This has led to a number of randomized clinical trials (RCT) with oral Cr supplementation, with durations up to 5 years. In this paper, we review the evidence and consequences stemming from these trials. In the case of PD, the initial phase II RCT was promising and led to a large and well-designed phase III trial, which, however, turned out to be negative for all outcome measures. None of the RCTs that have examined effects of Cr in ALS patients showed any clinical benefit. In HD, Cr in high doses (up to 30 g/day) was shown to slow down brain atrophy in premanifest Huntingtin mutation carriers. In spite of this, proof is still lacking that Cr can also have beneficial clinical effects in this group of patients, who will go on to develop HD symptoms. Taken together, the use of Cr supplementation has so far proved disappointing in clinical studies with a number of symptomatic neurodegenerative diseases.

  11. Bio-prospecting endemic Mascarene Aloes for potential neuroprotectants.

    Science.gov (United States)

    Lobine, D; Howes, M-J R; Cummins, I; Govinden-Soulange, J; Ranghoo-Sanmukhiya, M; Lindsey, K; Chazot, P L

    2017-12-01

    The Mascarene Aloes are used in the traditional pharmacopoeia against various ailments including cutaneous diseases and as antispasmodics. Scientific evidence to support these claims is non-existent and mainly based on the scientific repute of A. vera. The antioxidant profile of methanolic leaf extracts of A. purpurea Lam., A. tormentorii (Marais) L. E. Newton & G. D. Rowley, A. lomatophylloides Balf. f., A. macra Haw. and A. vera (L.) Burm. f. was studied using the total antioxidant capacity, copper equivalent and superoxide dismutase assays. In vitro cytotoxicity was evaluated on CAD (Cath.-a-differentiated) neuronal cells by the methyl tetrazolium assay, and the neuroprotective profile was assessed using hydrogen peroxide-induced neurotoxicity with the CAD cells. The aloin and vitexin content were determined by high-performance liquid chromatography with diode-array detection. A. purpurea had the highest aloin content (546.6 nmol/g), while A. tormentorii had the highest vitexin content (67.3 nmol/g). A. macra (concentration aloin and vitexin content that are also present in other reputed medicinal Aloes. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain.

    Science.gov (United States)

    Karimzadeh, Fariba; Hosseini, Mahmoud; Mangeng, Diana; Alavi, Hassan; Hassanzadeh, Gholam Reza; Bayat, Mohamad; Jafarian, Maryam; Kazemi, Hadi; Gorji, Ali

    2012-06-18

    Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain. Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  13. Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy

    Science.gov (United States)

    Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin

    2014-01-01

    Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes. PMID:24693424

  14. Zinc(II) binds to the neuroprotective peptide humanin.

    Science.gov (United States)

    Armas, Ambar; Sonois, Vanessa; Mothes, Emmanuelle; Mazarguil, Honoré; Faller, Peter

    2006-10-01

    The abnormal accumulation of the peptide amyloid-beta in the form of senile (or amyloid) plaques is one of the hallmarks of Alzheimer's disease (AD). Zinc ions have been implicated in AD and plaques formation. Recently, the peptide humanin has been discovered. Humanin showed neuroprotective activity against amyloid-beta insults. Here the question investigated is if humanin could interact directly with Zn(II). It is shown that Zn(II) and its substitutes Cd(II)/Co(II) bind to humanin via a thiolate bond from the side chain of the single cysteine at position 8. The low intensity of the d-d bands of Co(II)-humanin indicated an octahedral coordination geometry. Titration experiments suggest that Zn(II) binds to humanin with an apparent affinity in the low muM range. This apparent Zn-binding affinity is in the same order as for amyloid-beta and glutathione and could thus be of physiological relevance.

  15. Neuroprotection and Stroke Rehabilitation: Modulation and Enhancement of Recovery

    Directory of Open Access Journals (Sweden)

    José Rafael Romero

    2006-01-01

    Full Text Available Recent advances in research are modifying our view of recovery after nervous system damage. New findings are changing previously held concepts and providing promising avenues for treatment of patients after stroke. This review discusses mechanisms of neuronal injury after brain ischemia and the attempts to study neuroprotection options based on such mechanisms. It also considers measures available at present to improve outcome after stroke and presents new areas of research, particularly stimulation techniques, neurogenesis and trophic factors to enhance recovery. In order to improve outcomes, medications that may be detrimental to recovery should be avoided, while symptomatic therapy of problems such as depression, pain syndromes and spasticity may contribute to better results. Continued surveillance and early treatment of complications associated with acute stroke, along with supportive care remain the mainstay of treatment for stroke patients in the recovery phase. Present research on limiting brain damage and improving recovery and plasticity enhance the prospects for better clinical treatments to improve recovery after stroke.

  16. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  17. Transthyretin neuroprotection in Alzheimer's disease is dependent on proteolysis.

    Science.gov (United States)

    Silva, Catarina S; Eira, Jessica; Ribeiro, Carlos A; Oliveira, Ângela; Sousa, Mónica M; Cardoso, Isabel; Liz, Márcia A

    2017-11-01

    The deposition of amyloid β peptide (Aβ) in the hippocampus is one of the major hallmarks of Alzheimer's disease, a neurodegenerative disorder characterized by memory loss and cognitive impairment. The modulation of Aβ levels in the brain results from an equilibrium between its production from the amyloid precursor protein and removal by amyloid clearance proteins, which might occur via enzymatic (Aβ-degrading enzymes) or nonenzymatic (binding/transport proteins) reactions. Transthyretin (TTR) is one of the major Aβ-binding proteins acting as a neuroprotector in AD. In addition, TTR cleaves Aβ peptide in vitro. In this work, we show that proteolytically active TTR, and not the inactive form of the protein, impacts on Aβ fibrillogenesis, degrades neuronal-secreted Aβ, and reduces Aβ-induced toxicity in hippocampal neurons. Our data demonstrate that TTR proteolytic activity is required for the neuroprotective effect of the protein constituting a putative novel therapeutic target for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Modality of Input and Vocabulary Acquisition

    Science.gov (United States)

    Sydorenko, Tetyana

    2010-01-01

    This study examines the effect of input modality (video, audio, and captions, i.e., on-screen text in the same language as audio) on (a) the learning of written and aural word forms, (b) overall vocabulary gains, (c) attention to input, and (d) vocabulary learning strategies of beginning L2 learners. Twenty-six second-semester learners of Russian…

  19. Cross-Modal Binding in Developmental Dyslexia

    Science.gov (United States)

    Jones, Manon W.; Branigan, Holly P.; Parra, Mario A.; Logie, Robert H.

    2013-01-01

    The ability to learn visual-phonological associations is a unique predictor of word reading, and individuals with developmental dyslexia show impaired ability in learning these associations. In this study, we compared developmentally dyslexic and nondyslexic adults on their ability to form cross-modal associations (or "bindings") based…

  20. Refinement Checking on Parametric Modal Transition Systems

    DEFF Research Database (Denmark)

    Benes, Nikola; Kretínsky, Jan; Larsen, Kim Guldstrand

    2015-01-01

    Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refin...

  1. Dynamic analysis of pipings by Modal Synthesis

    International Nuclear Information System (INIS)

    Augusto, O.B.; Mattar Neto, M.

    1986-01-01

    A Modal Synthesis method, the component modes, and its implementation as a post-processor of finite element program is presented. Examples of calculations of stationary and transient vibrations for monitoring pipelines of nuclear power plants are analysed. (M.C.K.) [pt

  2. Established rheumatoid arthritis - new imaging modalities

    DEFF Research Database (Denmark)

    McQueen, Fiona M; Østergaard, Mikkel

    2007-01-01

    New imaging modalities are assuming an increasingly important role in the investigation and management of rheumatoid arthritis. It is now possible to obtain information about all tissues within the joint in three dimensions using tomographic techniques such as magnetic resonance imaging (MRI...

  3. Established rheumatoid arthritis - new imaging modalities

    DEFF Research Database (Denmark)

    McQueen, Fiona M; Østergaard, Mikkel

    2007-01-01

    New imaging modalities are assuming an increasingly important role in the investigation and management of rheumatoid arthritis. It is now possible to obtain information about all tissues within the joint in three dimensions using tomographic techniques such as magnetic resonance imaging (MRI) and...

  4. Computing modal dispersion characteristics of radially Asymmetric ...

    African Journals Online (AJOL)

    We developed a matrix theory that applies to with non-circular/circular but concentric layers fibers. And we compute the dispersion characteristics of radially unconventional fiber, known as Asymmetric Bragg fiber. An attempt has been made to determine how the modal characteristics change as circular Bragg fiber is ...

  5. MODALITIES OF TRAINING PARAMETER ALTERNATION IN NOWADAYS STRENGTH TRAINING PRACTICE

    Directory of Open Access Journals (Sweden)

    RANISAVLJEV IGOR

    2010-12-01

    Full Text Available Large number of variables could be alternated during the process of planning and programming in sports training. Superior training results in majority of sports are achieved by optimally manipulating training parameters in appropriate sequences and combinations. Additionally, in some sports they might be the result of appropriate periodization pattern. Today's tendency in strength training practice is training movements instead of training muscles. Exercise classification according to the dominant movement types, allows creating new modalities in training alternation. Additional variations in volume, intensity, rest brakes, repetition velocity andinter-repetition rest can be the important part of functional strength training program. Alternation and combination of different training parameters makes appropriate training stimulus for strength increase in the most of nowadays sports. Optimal alternation of basic training parameters should be the first part in the processof planning and programming. As a result, majority of athletes might not need advanced periodization patterns for optimal improvement in muscle strength and power

  6. Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress

    Directory of Open Access Journals (Sweden)

    C. Castillo

    2018-04-01

    Full Text Available Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR, it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL was purified from skimmed goat milk. Recombinant human erythropoietin (Epo was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1 h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP; cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15 min of oxygen and glucose deprivation (OGD and the neuroprotective drugs EpoL or Epo were incubated for 2 h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases. Keywords: Erythropoietin, Erythropoietin receptor, Neuroprotection, Oxidative stress

  7. PENGARUH GOOD CORPORATE GOVERNANCE, KINERJA KEUANGAN, MODAL INTELEKTUAL TERHADAP PENGUNGKAPAN MODAL INTELEKTUAL

    Directory of Open Access Journals (Sweden)

    Gilang Anies Saendy

    2015-10-01

    Full Text Available Dampak perkembangan globalisasi membutuhkan informasi lebih lanjut, terutama informasi tentang modal intelektual perusahaan. Tapi, dalam kondisi nyata informasi modal intelektual masih rendah, yakni sekitar 27-35%. Objek penelitian ini adalah perbankan yang terdapat dalam direktori Pasar Modal Indonesia (ICMD 2010-2013. Jumlah populasi adalah 36 perbankan dan 17 sampel dengan menggunakan purposive sampling. Metode yang digunakan adalah analisis jalur. Hasil penelitian ini menunjukkan bahwa tidak pengaruh antara pelaksanaan GCG untuk pengungkapan modal intelektual dan kinerja keuangan. Selain itu, ada pengaruh positif antara kinerja modal intelektual terhadap kinerja keuangan dan kinerja keuangan untuk pengungkapan modal intelektual. Selanjutnya, hasil penelitian menunjukkan bahwa tidak efek mediasi melalui kinerja keuangan perusahaan antara implementasi GCG dalam pengungkapan modal intelektual. Hasilnya juga mengatakan ada efek mediasi antara pelaksanaan GCG untuk pengungkapan modal intelektual pikir kinerja modal intelektual. The development due to the increase of globalization gives impact to the need of having more information. One of them is the need to have information on company’s intellectual capital. But, in real condition, intellectual capital information is still low. It is about 27-35%. The objects of this research are banks organized in Indonesian Capital Market Directory (ICMD from 2010-2013. Total populations were 36 banks, and finally 17 samples were selected by using purposive sampling. The method used is path analysis. The results of this research show that there is no influence between GCG’s implementation on intellectual capital disclosure and financial performance. However, there are  positive influences of intellectual capital performance on the financial performance, and financial performance on the disclosure of intellectual capital. Besides, this research said that there is no effect of mediation through the company

  8. Nonlinear Reduced-Order Simulation Using Stress-Free and Pre-Stressed Modal Bases

    Science.gov (United States)

    Przekop, Adam; Stover, Michael A.; Rizzi, Stephen A.

    2009-01-01

    A study is undertaken to determine the advantages and disadvantages associated with application of stress-free and pre-stressed modal bases in a reduced-order finite-element-based nonlinear simulation. A planar beam is chosen as an application example and its response due to combined thermal and random pressure loadings is examined. Combinations of two random pressure levels and two thermal conditions are investigated. The latter consists of an ambient temperature condition and an elevated temperature condition in the post-buckled regime. It is found that stress-free normal modes establish a broadly applicable modal basis yielding accurate results for all the loading regimes considered. In contrast, the range of applicability for a thermally pre-stressed modal basis is found to be limited. The behavior is explained by scrutinizing the coupling found in the linear stiffness and the effect this coupling has on the structural response characteristics under the range of loading conditions considered.

  9. The neuroprotective effects ofTao-Ren-Cheng-Qi Tangagainst embolic stroke in rats.

    Science.gov (United States)

    Hsu, Ling-Wei; Shiao, Wei-Cheng; Chang, Nen-Chung; Yu, Meng-Che; Yen, Ting-Lin; Thomas, Philip Aloysius; Jayakumar, Thanasekaran; Sheu, Joen-Rong

    2017-01-01

    Combinations of the traditional Chinese and Western medicines have been used to treat numerous diseases throughout the world, and there is a growing body of evidence showing that some of the herbs used in traditional Chinese medicine elicit significant pharmacological effects. The aim of this study was to demonstrate the neuroprotective effects of Tao - Ren - Cheng - Qi Tang (TRCQT) in combination with aspirin following middle cerebral artery occlusion (MCAO)-induced embolic stroke in rats. A blood clot was embolized into the middle cerebral artery of rats to induce focal ischemic brain injury. After 24 h of MCAO occlusion, the rats were arbitrarily separated into five groups and subjected to different oral treatment processes with TRCQT and aspirin for 30 days before being evaluated in terms of their neurological behavior using a four-point system. The rats were sacrificed at 30 days after drug treatment and the infarct volumes were measured using a 2,3,5-triphenyltetrazolium chloride staining method. Tumor necrosis factor-α (TNF-α), c-Jun N-terminal kinases (JNK), activated caspase-3 and Bax were detected by western blot analysis. The apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. ROS generation was also measured by electron spin resonance spectrometry. Rats treated with TRCQT alone or in combination with aspirin showed a significantly reduced infarct volume ( P  < 0.001) and improved neurological outcome compared with those treated with distilled water. Rats treated with TRCQT alone ( P  = 0.021) or in combination with aspirin ( P  = 0.02) also showed significantly reduced MCAO-induced expression levels of TNF-α and pJNK ( P  < 0.001) in their ischemic regions. Rats treated with TRCQT alone or in combination with aspirin showed decreased apoptosis by a reduction in the number of TUNEL positive cells, which inhibited the expression of activated caspase-3 ( P  = 0.038) and Bax ( P

  10. The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model.

    Directory of Open Access Journals (Sweden)

    Chul-Woong Woo

    Full Text Available Emerging evidence has suggested that hydrogen sulfide (H2S may alleviate the cellular damage associated with cerebral ischemia/reperfusion (I/R injury. In this study, we assessed using 1H-magnetic resonance imaging/magnetic resonance spectroscopy (1H-MRI/MRS and histologic analysis whether H2S administration prior to reperfusion has neuroprotective effects. We also evaluated for differences in the effects of H2S treatment at 2 time points. 1H-MRI/MRS data were obtained at baseline, and at 3, 9, and 24 h after ischemia from 4 groups: sham, control (I/R injury, sodium hydrosulfide (NaHS-30 and NaHS-1 (NaHS delivery at 30 and 1 min before reperfusion, respectively. The total infarct volume and the midline shift at 24 h post-ischemia were lowest in the NaHS-1, followed by the NaHS-30 and control groups. Peri-infarct volume was significantly lower in the NaHS-1 compared to NaHS-30 and control animals. The relative apparent diffusion coefficient (ADC in the peri-infarct region showed that the NaHS-1 group had significantly lower values compared to the NaHS-30 and control animals and that NaHS-1 rats showed significantly higher relative T2 values in the peri-infarct region compared to the controls. The relative ADC value, relative T2 value, levels of N-acetyl-L-aspartate (NAA, and the NAA, glutamate, and taurine combination score (NGT in the ischemic core region at 24 h post-ischemia did not differ significantly between the 2 NaHS groups and the control except that the NAA and NGT values were higher in the peri-infarct region of the NaHS-1 animals at 9 h post-ischemia. In the ischemic core and peri-infarct regions, the apoptosis rate was lowest in the NaHS-1 group, followed by the NaHS-30 and control groups. Our results suggest that H2S treatment has neuroprotective effects on the peri-infarct region during the evolution of I/R injury. Furthermore, our findings indicate that the administration of H2S immediately prior to reperfusion produces the

  11. [Neuroprotection for preterm infants with antenatal magnesium sulphate].

    Science.gov (United States)

    Marret, S; Ancel, P-Y

    2016-12-01

    To evaluate in preterm born children the neuroprotective benefits and the risks, at short- and long-term outcome, of the antenatal administration of magnesium sulphate (MgSO 4 ) in women at imminent risk of preterm delivery. Computer databases Medline, the Cochrane Library and the recommendations of various international scientific societies. Given the demonstrated benefit of antenatal MgSO 4 intravenous administration on the reduction of cerebral palsy rates and the improvement of motor development in children born preterm, it is recommended for all women whose imminent delivery is expected or programmed before 32 weeks of gestation (WG) (grade A). The analysis of the literature finds no argument for greater benefit of antenatal MgSO 4 administration in sub-groups of gestational age, or depending on the type of pregnancy (single or multiple pregnancy) or with the cause of preterm birth (NP2). Its administration is recommended before 32 WG, if single or multiple pregnancy, whatever the cause of prematurity (grade B). It is recommended 4g loading dose (professional consensus). With a loading dose of 4g intravenous (IV) in 20min, the serum magnesium is lower than with intramuscular suggesting a preference for the IV route (professional consensus). It is proposed to use a maintenance dose of 1g/h until delivery with a maximum recommended duration of 12hours without exceeding a cumulative dose of 50g (professional consensus). These doses are without severe adverse maternal side effects or adverse effects in newborns at short- and medium-term outcome (NP1). It is recommended to administer magnesium sulfate to the women at high risk of imminent preterm birth before 32 WG, whether expected or planned (grade A), with a 4g IV loading dose followed by a maintenance dose of 1g/h for 12hours (professional consensus), the pregnancy is single or multiple, whatever the cause of prematurity (professional consensus). Copyright © 2016. Published by Elsevier Masson SAS.

  12. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  13. Neuroprotective Role of Lazaroids Against Aluminium Chloride Poisoning.

    Science.gov (United States)

    Sood, Pooja Khanna; Verma, Sonia; Nahar, Uma; Nehru, Bimla

    2015-08-01

    Aluminium (Al) is neurotoxic primarily because of its interference with biological enzymes in key mechanisms of metabolic pathways. Mitochondria being a major site of reactive oxygen species (ROS) production, it seems that the oxidative damage to mitochondrial proteins may underlie the pathogenesis of Al induced neurodegeneration. The present study investigates the effectiveness of the anti-oxidant property of lazaroids (U-74500A), a known lipid peroxidation inhibitor as neuroprotective agent against Al induced neurotoxicity. Al chloride was administered orally at a dose level of 100 mg/kg body wt/day in water and U-74500A was administered at a dose of 0.25 mg/kg body wt i.p. in citrate buffer for a period of 8 weeks on alternate days. Following Al exposure there was a significant increase in lipid peroxidation (LPO), ROS levels and reduction in the activity of mitochondrial complexes in all the three regions of rat brain, i.e., cerebral cortex, mid brain, and cerebellum. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria. These alterations were also depicted in the histology which shows signs of hypoxia, paucity of neurons in cortical region and loosening of fibers in the white matter. U-74500A co-administration was able to restore alterations in the LPO, ROS levels as well as all the three mitochondrial complexes and caspase expression. Therefore, it is suggested that 21-aminosteroids (lazaroids), by attenuating LPO and mitochondrial dysfunction, holds a promise as an agent that can potentially reduce Al-induced adverse effects in brain.

  14. Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Kumfu, Sirinart; Charununtakorn, Savitree T; Jaiwongkam, Thidarat; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-01-01

     Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R injury. In a clinical setting, patients received medical treatment for acute myocardial infarction either during or after the onset of myocardial ischemia; thus, in this study, we tested the hypothesis that the administration of HNG during cardiac I/R injury has therapeutic potential for brain protection. Thirty-six male Wistar rats were divided into two groups: a cardiac I/R group (n = 30), and a sham group (n = 6). The I/R rats were then divided into five subgroups to receive: 1) vehicle; 2) HNG (84 μg/kg); 3) HNG (168 μg/kg); 4) HNG (252 μg/kg) intravenously administered during the cardiac-ischemia; and 5) HNG at 252 μg/kg given at the onset of reperfusion. At the end of treatment, brains were removed for determination of blood-brain barrier (BBB) breakdown, oxidative stress, brain mitochondrial function, brain mitochondrial dynamics, p-tau, amyloid-β (Aβ) and apoptosis. HNG at a dose of 168 and 252 μg/kg administered during ischemia, and 252 μg/kg given at the onset of reperfusion effectively attenuated the brain mitochondrial dysfunction, tau hyperphosphorylation and Aβ accumulation, and apoptosis, without reducing BBB breakdown, brain oxidative stress, or mitochondrial dynamic, caused by cardiac I/R injury. In conclusion, humanin exerted neuroprotection during induced cardiac I/R injury via improvement in brain mitochondrial function, and the reduction of Alzheimer's disease pathology and apoptosis.

  15. Cytochrome C is tyrosine 97 phosphorylated by neuroprotective insulin treatment.

    Directory of Open Access Journals (Sweden)

    Thomas H Sanderson

    Full Text Available Recent advancements in isolation techniques for cytochrome c (Cytc have allowed us to discover post-translational modifications of this protein. We previously identified two distinct tyrosine phosphorylated residues on Cytc in mammalian liver and heart that alter its electron transfer kinetics and the ability to induce apoptosis. Here we investigated the phosphorylation status of Cytc in ischemic brain and sought to determine if insulin-induced neuroprotection and inhibition of Cytc release was associated with phosphorylation of Cytc. Using an animal model of global brain ischemia, we found a ∼50% decrease in neuronal death in the CA1 hippocampal region with post-ischemic insulin administration. This insulin-mediated increase in neuronal survival was associated with inhibition of Cytc release at 24 hours of reperfusion. To investigate possible changes in the phosphorylation state of Cytc we first isolated the protein from ischemic pig brain and brain that was treated with insulin. Ischemic brains demonstrated no detectable tyrosine phosphorylation. In contrast Cytc isolated from brains treated with insulin showed robust phosphorylation of Cytc, and the phosphorylation site was unambiguously identified as Tyr97 by immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry. We next confirmed these results in rats by in vivo application of insulin in the absence or presence of global brain ischemia and determined that Cytc Tyr97-phosphorylation is strongly induced under both conditions but cannot be detected in untreated controls. These data suggest a mechanism whereby Cytc is targeted for phosphorylation by insulin signaling, which may prevent its release from the mitochondria and the induction of apoptosis.

  16. Progranulin and Its Related MicroRNAs after Status Epilepticus: Possible Mechanisms of Neuroprotection

    Directory of Open Access Journals (Sweden)

    Peter Körtvelyessy

    2017-02-01

    Full Text Available The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus.

  17. Morphological functional criteria of neuroprotective therapy efficacy in glaucomatous optic neuropathy

    Directory of Open Access Journals (Sweden)

    Tszin Dan

    2015-01-01

    Full Text Available Electrophysiological tests may be used to detect early glaucomatous changes and glaucoma progression risk and to monitor treatment efficacy. Most important pathogenic aspects of glaucomatous process, pathogenesis and multifactorial nature of glaucomatous optic neuropathy are described. Major triggers of glaucomatous optic neuropathy are mechanical and vascular. Principles of neuroprotective therapy, neuroprotective drugs, and mechanisms of action of direct and indirect neuroprotective agents are presented. IOPcc is a basis for neuroprotective therapy selection and its efficacy monitoring. Amongst neuroprotective drugs, NMDA agonists, antioxidants, peptides, and calcium channel blockers are of special importance. Structural damage and functional deficiency (e.g., visual field loss in glaucoma and the most informative and accurate methods of their detection are characterized. Confocal laser microscopy, optical coherence tomography, and scanning laser polarimetry are compared. These techniques are used to study optic nerve head and retinal nerve fiber layer. They are proposed as diagnostic and monitoring tools for glaucoma, glaucoma suspicion, and ocular hypertension. The most sensitive and specific electrophysiological tests for glaucomatous optic neuropathy are pattern electroretinography, multfocal electroretinography, and multifocal visually evoked potentials. 

  18. Tetrahydroxystilbene Glucoside Produces Neuroprotection against 6-OHDA-Induced Dopamine Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Chun Huang

    2018-01-01

    Full Text Available Parkinson’s disease (PD was one of the most common neurodegenerative diseases with a slow and progressive loss of dopamine (DA neurons in the midbrain substantia nigra (SN. Neuroinflammation was identified to be an important contributor to PD pathogenesis with the hallmark of microglia activation. Tetrahydroxystilbene glucoside (TSG was the main active component extracted from Polygonum multiflorum and held amounts of pharmacological activities including antioxidant, free radical-scavenging, anti-inflammation, and cardioprotective properties. Recent studies demonstrated that TSG exerted neuroprotection from several neurodegenerative disease models. However, the underlying mechanisms were not completely elucidated. In the present study, rat nigral stereotaxic injection of 6-hydroxydopamine- (6-OHDA- elicited DA neuronal injury was performed to investigate TSG-mediated neuroprotection on DA neurons. In addition, primary rat midbrain neuron-glia cocultures were applied to explore the mechanisms underlying TSG-exerted neuroprotection. Results showed that daily intraperitoneal injection of TSG for 14 consecutive days significantly protected DA neurons from 6-OHDA-induced neurotoxicity and suppressed microglia activation. Similar neuroprotection was shown in primary neuron-glia cocultures. In vitro studies further demonstrated that TSG inhibited microglia activation and subsequent release of proinflammatory factors. Moreover, TSG-mediated neuroprotection was closely related with the inactivation of mitogen-activated protein kinase (MAPK signaling pathway. Together, TSG protects DA neurons from 6-OHDA-induced neurotoxicity via the inhibition of microglia-elicited neuroinflammation. These findings suggest that TSG might hold potential therapeutic effects on PD.

  19. Supervised Cross-Modal Factor Analysis for Multiple Modal Data Classification

    KAUST Repository

    Wang, Jingbin

    2015-10-09

    In this paper we study the problem of learning from multiple modal data for purpose of document classification. In this problem, each document is composed two different modals of data, i.e., An image and a text. Cross-modal factor analysis (CFA) has been proposed to project the two different modals of data to a shared data space, so that the classification of a image or a text can be performed directly in this space. A disadvantage of CFA is that it has ignored the supervision information. In this paper, we improve CFA by incorporating the supervision information to represent and classify both image and text modals of documents. We project both image and text data to a shared data space by factor analysis, and then train a class label predictor in the shared space to use the class label information. The factor analysis parameter and the predictor parameter are learned jointly by solving one single objective function. With this objective function, we minimize the distance between the projections of image and text of the same document, and the classification error of the projection measured by hinge loss function. The objective function is optimized by an alternate optimization strategy in an iterative algorithm. Experiments in two different multiple modal document data sets show the advantage of the proposed algorithm over other CFA methods.

  20. Modal Testing of Mechanical Structures subject to Operational Excitation Forces

    DEFF Research Database (Denmark)

    Møller, N.; Brincker, Rune; Herlufsen, H.

    2001-01-01

    Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need to be appl......Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need...

  1. Open-geometry Fourier modal method: modeling nanophotonic structures in infinite domains

    DEFF Research Database (Denmark)

    Häyrynen, Teppo; de Lasson, Jakob Rosenkrantz; Gregersen, Niels

    2016-01-01

    We present an open-geometry Fourier modal method based on a new combination of open boundary conditions and an efficient k-space discretization. The open boundary of the computational domain is obtained using basis functions that expand the whole space, and the integrals subsequently appearing due...

  2. Comparing effects of tobacco use prevention modalities: need for complex system models

    Directory of Open Access Journals (Sweden)

    Sussman Steve

    2013-01-01

    Full Text Available Abstract Many modalities of tobacco use prevention programming have been implemented including various policy regulations (tax increases, warning labels, limits on access, smoke-free policies, and restrictions on marketing, mass media programming, school-based classroom education, family involvement, and involvement of community agents (i.e., medical, social, political. The present manuscript provides a glance at these modalities to compare relative and combined impact of them on youth tobacco use. In a majority of trials, community-wide programming, which includes multiple modalities, has not been found to achieve impacts greater than single modality programming. Possibly, the most effective means of prevention involves a careful selection of program type combinations. Also, it is likely that a mechanism for coordinating maximally across program types (e.g., staging of programming is needed to encourage a synergistic impact. Studying tobacco use prevention as a complex system is considered as a means to maximize effects from combinations of prevention types. Future studies will need to more systematically consider the role of combined programming.

  3. Focus of Attention and Choice of Text Modality in Multimedia Learning

    Science.gov (United States)

    Schnotz, Wolfgang; Mengelkamp, Christoph; Baadte, Christiane; Hauck, Georg

    2014-01-01

    The term "modality effect" in multimedia learning means that students learn better from pictures combined with spoken rather than written text. The most prominent explanations refer to the split attention between visual text reading and picture observation which could affect transfer of information into working memory, maintenance of…

  4. Modal instability of rod fiber amplifiers: a semi-analytic approach

    DEFF Research Database (Denmark)

    Jørgensen, Mette Marie; Hansen, Kristian Rymann; Laurila, Marko

    2013-01-01

    The modal instability (MI) threshold is estimated for four rod fiber designs by combining a semi-analytic model with the finite element method. The thermal load due to the quantum defect is calculated and used to numerically determine the mode distributions on which the expression for the onset o...

  5. Established rheumatoid arthritis - new imaging modalities

    DEFF Research Database (Denmark)

    McQueen, Fiona M; Østergaard, Mikkel

    2007-01-01

    ) and high-resolution computerized tomography. Erosions are very clearly depicted using these modalities and MRI also allows imaging of soft tissues with assessment of joint inflammation. High-resolution ultrasound is a convenient clinical technique for the assessment of erosions, synovitis and tenosynovitis...... in real-time and facilitates diagnostic and therapeutic interventions such as joint aspiration and injection. Exciting experimental modalities are also being developed with the potential to provide not just morphological but functional imaging. Techniques such as positron emission tomography (PET......) and single photon emission tomography (SPECT) can reveal actively metabolizing bone and the proliferation of synovial cells via radioactive labeling. Bioluminescence and fluorescence reflectance imaging are other approaches that allow imaging, and potentially the delivery of therapeutic agents...

  6. Kinetic Study of Curcumin on Modal Fabric

    Directory of Open Access Journals (Sweden)

    Abu Naser Md. Ahsanul Haque

    2018-03-01

    Full Text Available A kinetic study of curcumin on modal fabric was carried out using an initial dye concentration of 1 g/L at three different temperatures, 70 °C, 85 °C and 100 °C, at pH 7 and an material to liquor ratio of 1:20. Pseudo first-order and pseudo second-order kinetics were applied, and it was found that the adsorption kinetics of curcumin on modal fabric matched the pseudo second-order kinetic model. The activation energy was found to be equal to 71.14 kJ/mol, while the enthalpy and entropy of activation were 68.16 kJ/mol and –66.02 J/molK respectively.

  7. Model Design of Piezoelectric Micromachined Modal Gyroscope

    Directory of Open Access Journals (Sweden)

    Xiaojun Hu

    2011-01-01

    Full Text Available This paper reports a novel kind of solid-state microgyroscope, which is called piezoelectric micromachined modal gyroscope (PMMG. PMMG has large stiffness and robust resistance to shake and strike because there is no evident mass-spring component in its structure. This work focused on quantitative optimization of the gyroscope, which is still blank for such gyroscope. The modal analysis by the finite element method (FEM was firstly conducted. A set of quantitative indicators were developed to optimize the operation mode. By FEM, the harmonic analysis was conducted to find the way to efficiently actuate the operational mode needed. The optimal configuration of driving electrodes was obtained. At last, the Coriolis analysis was conducted to show the relation between angular velocity and differential output voltage by the Coriolis force under working condition. The results obtained in this paper provide theoretical basis for realizing this novel kind of micromachined gyroscope.

  8. Deception Detection, Transmission, & Modality in Age & Sex

    Directory of Open Access Journals (Sweden)

    Charlotte Dorothy Sweeney

    2014-06-01

    Full Text Available This study is the first to create and use spontaneous (i.e. unrehearsed pro-social lies in an ecological setting. Creation of the stimuli involved fifty-one older adult and forty-four college student senders who lied authentically in that their lies were spontaneous in the service of protecting a research assistant. In the main study, seventy-seven older adult and eighty-four college raters attempted to detect lies in the older adult and college senders in three modalities: audio, visual, and audiovisual. Raters of both age groups were best at detecting lies in the audiovisual and worst in the visual modalities. Overall, college students were better detectors than older adults. There was an age-matching effect for college students but not for older adults. Older adult males were the hardest to detect. The older the adult was the worse the ability to detect deception.

  9. Modal Based Fatigue Monitoring of Steel Structures

    DEFF Research Database (Denmark)

    Graugaard-Jensen, J.; Brincker, Rune; Hjelm, H. P.

    2005-01-01

    In this paper it is shown how the accumulated fatigue in steel structures can be estimated with high accuracy by continuously measuring the accelerations in a few points of the structure. First step is to obtain a good estimate of the mode shapes by performing a natural input modal analysis. The so...... the damage forecasted by commonly accepted design rules. This points to possibilities of significantly increasing the fatigue lives of structures by performing continuous monitoring....... obtained mode shapes are then used to calibrate a Finite Element model of the structure and to obtain the modal coordinates of the active modes by inverting the mode shape matrix. If the number of active modes is smaller than the number of measurement points, then the problem is solved by regression...

  10. The life trajectories modality of oral history

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Gonçalves

    2007-05-01

    Full Text Available This article seeks to explore the potential of qualitative research. It presents the life trajectory modality of the oral history method, to discuss the possibility of its utilization in scientific research in the Social Work profession. The epistemological foundations of oral history are discussed to establish its scientific character. The life trajectories modality is presented as a historic and social construction that utilizes different interview techniques to give voice to previously invisible subjects, indicating the principal phases of the methodological procedures used in this approach. The conclusions highlight the importance of the construction of this model and its projection as a research proposal that implies a process of understanding and analyzing the social universes that are contextualized and interconnected, considering the realities of the life trajectories of the subjects studied.

  11. Neuroprotective Effect of Coptis chinensis in MPP[Formula: see text] and MPTP-Induced Parkinson's Disease Models.

    Science.gov (United States)

    Friedemann, Thomas; Ying, Yue; Wang, Weigang; Kramer, Edgar R; Schumacher, Udo; Fei, Jian; Schröder, Sven

    2016-01-01

    The rhizome of Coptis chinensis is commonly used in traditional Chinese medicine alone or in combination with other herbs to treat diseases characterized by causing oxidative stress including inflammatory diseases, diabetes mellitus and neurodegenerative diseases. In particular, there is emerging evidence that Coptis chinensis is effective in the treatment of neurodegenerative diseases associated with oxidative stress. Hence, the aim of this study was to investigate the neuroprotective effect of Coptis chinensis in vitro and in vivo using MPP[Formula: see text] and MPTP models of Parkinson's disease. MPP[Formula: see text] treated human SH-SY5Y neuroblastoma cells were used as a cell model of Parkinson's disease. A 24[Formula: see text]h pre-treatment of the cells with the watery extract of Coptis chinensis significantly increased cell viability, as well as the intracellular ATP concentration and attenuated apoptosis compared to the MPP[Formula: see text] control. Further experiments with the main alkaloids of Coptidis chinensis, berberine, coptisine, jaterorrhizine and palmatine revealed that berberine and coptisine were the main active compounds responsible for the observed neuroprotective effect. However, the full extract of Coptis chinensis was more effective than the tested single alkaloids. In the MPTP-induced animal model of Parkinson's disease, Coptis chinensis dose-dependently improved motor functions and increased tyrosine hydroxylase-positive neurons in the substantia nigra compared to the MPTP control. Based on the results of this work, Coptis chinensis and its main alkaloids could be considered potential candidates for the development of new treatment options for Parkinson's disease.

  12. Multi modal child-to-child interaction

    DEFF Research Database (Denmark)

    Fisker, Tine Basse

    In this presentation the interaction and relation of three boys is analyzed using multi modal analysis. The analysis clearly, and surprisingly demonstrates that the boys interact via different modes and that they are able to handle several interaction partners at the same time. They co-construct ......-construct interaction in rather complex and unexpected ways using verbal as well as non-verbal modes in interaction....

  13. Application of modalities in overuse syndromes.

    Science.gov (United States)

    Gieck, J H; Saliba, E N

    1987-04-01

    Improper techniques are often the cause of overuse syndromes. Unless the technique is corrected, the patient is doomed to recurrence. The same is true of improper posture, especially in the lower extremity and trunk areas. The pitcher or tennis player should have his or her style analyzed for proper form. The runner should have his or her muscular imbalances corrected by exercise and orthotic appliances. As with all other modalities used for treating painful conditions, proper evaluation of the etiology and the rectification of the cause is important. When athletes are underway in their sports seasons, it is often difficult to convince them to accept the ideal healing conditions needed to eliminate the problem. Management of the condition with any modality while maintaining an active lifestyle often brings about ethical scrutiny. However, it is the belief of the authors that noninvasive modalities do not provide the pain relief that would enable the athlete to tolerate activity beyond a significant injurious stress level. The modalities allow the athlete to regain the criteria for return, strength, and range of motion more successfully. Short-term goal setting is imperative to proper return. Several plateaus should be successfully completed before full return to activity is allowed. Tennis elbow, for example, may be allowed an initial period of 5 minutes on alternate days, gradually increasing to full activity every other day. Patients are often so anxious to return to activity that they overdo, leading to a decrease in function with a rapid return to the results of inflammation. The goals of successful rehabilitation of the overuse syndrome are pain-free range of motion, strength, and endurance. The use of cold, heat, electrotherapy, and exercise allow the athlete to reach his or her goal of returning to activity more quickly with a reduced risk of reinjury.

  14. Aspectos particularistas en el discurso modal

    Directory of Open Access Journals (Sweden)

    Manuel PÉREZ OTERO

    2010-01-01

    Full Text Available Según el particularismo semántico modal la función referencial de los términos singulares —también cuando aparecen en enunciados modales— es irreducible mediante funciones descriptivas y lógicas. Kripke es quien ha defendido vigorosamente esa tesis; elucidamos en ese sentido su rechazo a cierta interpretación metafórica de los mundos posibles como lugares lejanos vistos con telescopios.

  15. Estimation of Modal Parameters and their Uncertainties

    DEFF Research Database (Denmark)

    Andersen, P.; Brincker, Rune

    1999-01-01

    In this paper it is shown how to estimate the modal parameters as well as their uncertainties using the prediction error method of a dynamic system on the basis of uotput measurements only. The estimation scheme is assessed by means of a simulation study. As a part of the introduction, an example...... is given showing how the uncertainty estimates can be used in applications such as damage detection....

  16. Rules with parameters in modal logic I

    Czech Academy of Sciences Publication Activity Database

    Jeřábek, Emil

    2015-01-01

    Roč. 166, č. 9 (2015), s. 881-933 ISSN 0168-0072 R&D Projects: GA AV ČR IAA100190902; GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : modal logic * admissible rule * equational unification Subject RIV: BA - General Mathematics Impact factor: 0.582, year: 2015 http://www.sciencedirect.com/science/article/pii/S0168007215000366

  17. Mobile Active Authentication via Linguistic Modalities

    Science.gov (United States)

    2015-07-01

    keyboard, (2) applications used, (3) websites visited, and (4) physical location of the device as determined from GPS (when outdoors) or WiFi (when...visited. • Location (based on GPS or WiFi ). The key characteristics of this dataset are its large size (200 users), the duration of tracked activity (30...either from GPS or WiFi . Table 2 shows statistics on each of the four investigated modalities in the corpus. The table contains data aggregated

  18. Seven new sesquineolignans isolated from the seeds of hawthorn and their neuroprotective activities.

    Science.gov (United States)

    Huang, Xiao-Xiao; Ren, Qiang; Song, Xiao-Yu; Zhou, Le; Yao, Guo-Dong; Wang, Xiao-Bo; Song, Shao-Jiang

    2018-03-01

    Seven new sesquineolignans (1-7) were isolated from the 70% ethanolic extract of the hawthorn seeds. Their structures were established by comprehensive spectroscopic analyses including 1D, 2D NMR, CD and HRESIMS data. The neuroprotective activity of the isolated sesquilignans towards H 2 O 2 -induced damage in human neuroblastoma SH-SY5Y cells was investigated. All of these sesquineolignans exhibited significant neuroprotective activity towards damaged SH-SY5Y cells, compared with the positive control (Trolox). Among them, 6 displayed the most potent neuroprotective ability with the survival rate of 90.74% at the concentration of 50μM. Moreover, Hoechst 33258 staining and Annexin V/PI analysis proved that 6 could protect damaged SH-SY5Y cells through inhibiting cellular apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Angiotensin II Type 2 Receptor Agonist Experts Sustained Neuroprotective Effects In Aged Rats

    DEFF Research Database (Denmark)

    Sumners, Colin; Isenberg, Jacob; Harmel, Allison

    2016-01-01

    OBJECTIVE: The renin angiotensin system is a promising target for stroke neuroprotection and therapy through activation of angiotensin type II receptors (AT2R). The selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exhibit neuroprotection and improve stroke outcomes...... in preclinical studies, effects that likely involve neurotropic actions. However, these beneficial actions of C21 have not been demonstrated to occur beyond 1 week post stroke. The objective of this study was to determine if systemic administration of C21 would exert sustained neuroprotective effects in aged...... min), 24 h, and 48 h after stroke. Infarct size was assessed by magnetic resonance imaging at 21 days post MCAO. Animals received blinded neurological exams at 4 h, 24 h, 72 h, 7d, 14d, and 21d post-MCAO. RESULTS: Systemic treatment with C21 after stroke significantly improved neurological function...

  20. Use of a wire extender during neuroprotected vertebral artery angioplasty and stenting.

    Science.gov (United States)

    Lesley, Walter S; Kumar, Ravi; Rangaswamy, Rajesh

    2010-09-01

    The off-label use of an extender wire during vertebral artery stenting and angioplasty with or with neuroprotection has not been previously reported. Retrospective, single-patient, technical report. After monorail balloon angioplasty was performed on a proximal left vertebral artery stenosis, the 190 cm long Accunet neuroprotection filter device was not long enough for delivery of an over-the-wire stent. After mating a 145 cm long, 0.014 inch extension wire to the filter device, a balloon-mounted Liberté stent was implanted with good angiographic and clinical results. The off-label use of an extender wire permits successful over-the-wire stenting on a monorail neuroprotection device for vertebral artery endosurgery.