WorldWideScience

Sample records for pre-release therapeutic treatment

  1. Criminally Committed Inpatients in a Residential Forensic Pre-Release Treatment Program: An Exploratory Study.

    Science.gov (United States)

    Koetting, Mark G.; Grabarek, Joanna; Van Hasselt, Vincent B.; Hazelwood, Robert R.

    2003-01-01

    Investigation was conducted into the demographic, psychopathological, and offense characteristics of forensic psychiatric patients in residential treatment program. Descriptive findings, including victim variables, are presented. Select case vignettes, including offense profiles, are described. Clinical implications for risk assessment and…

  2. SHAKER Version 0.0/5 Pre-release Notes

    CERN Document Server

    CERN. Geneva

    1993-01-01

    SHAKER V0.0/5 is a pre-release of a simple cocktail central rapidity phase space event generator developed for the simulation of LHC Heavy Ion events. A modified version of JETSET 7.3 (the / LUJETS / common has been enlarged to 50000 particles and the LUEDIT routine has been modified to rearrange the particle weights vectors when called with MEDIT=1) is used to manage the events. All event information is included in / LUJETS / according to Lund conventions [1].

  3. Expected shortage based pre-release strategy for reservoir flood control

    Science.gov (United States)

    Chou, Frederick N.-F.; Wu, Chia-Wen

    2013-08-01

    In Taiwan, an increase in the frequency of severe flooding over the past decade has prompted demand for improved reservoir operation to control flood-related damage. Flood protection of reservoir can be enhanced by pre-releasing its storage to more adequately accommodate an impending flood. A procedure is proposed in this paper to evaluate the impact of pre-releases of flood control operation on water supply. A basic criterion used is that the pre-release of reservoir storage should not cause intolerable increment of water shortage risk. The shortage risks for different pre-release scenarios are simulated according to the uncertainties of storm rainfall and post-flood ordinary inflow till the end of next dry season. Two operational objectives are provided to help determining the target pre-released level. One of which identifies the minimum allowable pre-released threshold. The other seeks the pre-released level which maximizes the probability that the reservoir release during flood is below the non-damaging discharge and the end-of-operation storage target can still be achieved. This paper evaluated the operations of Tsengwen Reservoir of southern Taiwan during four typhoons from 2007 to 2012 to illustrate the significant contribution of pre-releases in reducing downstream flood potential.

  4. Nanoparticle therapeutics for prostate cancer treatment.

    Science.gov (United States)

    Sanna, Vanna; Sechi, Mario

    2012-09-01

    The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. There is a substantial interest in developing therapeutic options for treatment of prostate cancer based on use of nanodevices, to overcome the lack of specificity of conventional chemotherapeutic agents as well as for the early detection of precancerous and malignant lesions. Herein, we highlight on the recent development of nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-014, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy. However, several limitations facing nanoparticle delivery to solid tumours, such as heterogeneity of intratumoural barriers and vasculature, cytotoxicity and/or hypersensitivity reactions to currently available cancer nanomedicines, and the difficult in developing targeted nanoparticles with optimal biophysicochemical properties, should be still addressed for a successful tumour eradication. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Mechanism of preventing coal and gas compression disseminated values outburst with stress pre-released hydraulically

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zhong-fei; Yu, Qi-xiang [Jiangsu University, Zhenjiang (China). Center of Safety Engineering

    2007-01-15

    Based on the conditions of coal and gas outburst, the action mechanism for preventing coal and gas compression disseminated values outburst with stress pre-released hydraulically was analyzed. The accuracy of this mechanism was validated by measuring the gas emission before and after pre-releasing stress hydraulically, measuring the rupture failure by the electromagnetic radiation technique and the correlative practical datum. The results show that the electromagnetic radiation intensity and pulse count are increscent when taking the measure of stress pre-released hydraulically, which is propitious to prevent the coal and gas outburst. The action mechanism consists of three aspects: 1) Pre-releasing gas and increasing tangential stress and disseminated values friction resistance; 2) Pre-releaseing the radial effective geostress on high-tension side and reducing the radial stress difference of disseminated values chop motion for enhancing coal displacement; 3) Making the disseminated values and adjacent coal and rock felting by flooding water and increasing the disseminated values' friction resistance coefficients. 9 refs., 2 figs.

  6. Hepatocellular Carcinoma: Therapeutic Guidelines and Medical Treatment

    Science.gov (United States)

    Kudo, Masatoshi; Trevisani, Franco; Abou-Alfa, Ghassan K; Rimassa, Lorenza

    2016-01-01

    Western and Eastern perspectives on therapeutic guidelines for hepatocellular carcinoma (HCC) have many commonalities but may also differ in certain aspects, as described in this article. In view of the limited therapeutic options for advanced HCC, evidence-based therapies are few, and thus there is a dependence on consensus-based guidelines. This article focuses on the Italian Association for the Study of the Liver guidelines and the Japanese approaches to therapy, while drawing attention to certain controversies from other academic bodies where applicable and appropriate. PMID:27995084

  7. Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

    Science.gov (United States)

    Abdel-Salam, Sami; Gunter, Whitney D.

    2014-01-01

    The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

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

    Science.gov (United States)

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

    2009-01-01

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

  9. Evaluation of Therapeutic Effects of Radiotherapy during Treatment ...

    African Journals Online (AJOL)

    therapeutic effects of radiotherapy during treatment of lung adenocarcinoma. Methods: Eighteen mice with .... reconstruction of the cross-sectional images of the coronal plane .... breast tumor from mediastinal metastases to further improve the ...

  10. DNAzyme-based therapeutics for cancer treatment.

    Science.gov (United States)

    Fu, Shujun; Sun, Lun-Quan

    2015-01-01

    Gene-silencing strategies based on catalytic nucleic acids have been rapidly developed in the past decades. Ribozymes, antisense oligonucleotides and RNA interference have been actively pursued for years due to their potential application in gene inactivation. Pioneered by Joyce et al., a new class of catalytic nucleic acid composed of deoxyribonucleotides has emerged via an in vitro selection system. The therapeutic potential of these RNA-cleaving DNAzymes have been shown both in vitro and in vivo. Although they rival the activity and stability of synthetic ribozymes, they are limited by inefficient delivery to the intracellular targets. Recent successes in clinical testing of the DNAzymes in cancer patients have revitalized the potential clinical utility of DNAzymes.

  11. Therapeutic options for treatment-resistant depression.

    Science.gov (United States)

    Shelton, Richard C; Osuntokun, Olawale; Heinloth, Alexandra N; Corya, Sara A

    2010-02-01

    Treatment-resistant depression (TRD) presents major challenges for both patients and clinicians. There is no universally accepted definition of TRD, but results from the US National Institute of Mental Health's (NIMH) STAR*D (Sequenced Treatment Alternatives to Relieve Depression) programme indicate that after the failure of two treatment trials, the chances of remission decrease significantly. Several pharmacological and nonpharmacological treatments for TRD may be considered when optimized (adequate dose and duration) therapy has not produced a successful outcome and a patient is classified as resistant to treatment. Nonpharmacological strategies include psychotherapy (often in conjunction with pharmacotherapy), electroconvulsive therapy and vagus nerve stimulation. The US FDA recently approved vagus nerve stimulation as adjunctive therapy (after four prior treatment failures); however, its benefits are seen only after prolonged (up to 1 year) use. Other nonpharmacological options, such as repetitive transcranial stimulation, deep brain stimulation or psychosurgery, remain experimental and are not widely available. Pharmacological treatments of TRD can be grouped in two main categories: 'switching' or 'combining'. In the first, treatment is switched within and between classes of compounds. The benefits of switching include avoidance of polypharmacy, a narrower range of treatment-emergent adverse events and lower costs. An inherent disadvantage of any switching strategy is that partial treatment responses resulting from the initial treatment might be lost by its discontinuation in favour of another medication trial. Monotherapy switches have also been shown to have limited effectiveness in achieving remission. The advantage of combination strategies is the potential to build upon achieved improvements; they are generally recommended if partial response was achieved with the current treatment trial. Various non-antidepressant augmenting agents, such as lithium and

  12. Novel Therapeutic Target for the Treatment of Lupus

    Science.gov (United States)

    2014-09-01

    AWARD NUMBER: W81XWH-12-1-0205 TITLE: Novel Therapeutic Target for the Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop...SUBTITLE 5a. CONTRACT NUMBER Novel Therapeutic Target for the Treatment of Lupus 5b. GRANT NUMBER W81XWH-12-1-0205 5c. PROGRAM ELEMENT NUMBER 6...Systemic lupus erythematosus, autoantibodies. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 7 19a. NAME OF

  13. A Web Based Framework for Pre-release Testing of Mobile Applications

    Directory of Open Access Journals (Sweden)

    Hamdy Abeer

    2016-01-01

    Full Text Available Mobile applications are becoming an integral part of daily life and of business’s marketing plan. They are helpful in promoting for the business, attracting and retaining customers. Software testing is vital to ensure the delivery of high quality mobile applications that could be accessed across different platforms and meet business and technical requirements. This paper proposes a web based tool, namely Pons, for the distribution of pre-release mobile applications for the purpose of manual testing. Pons facilities building, running, and manually testing Android applications directly in the browser. It gets the developers and end users engaged in testing the applications in one place, alleviates the tester’s burden of installing and maintaining testing environments, and provides a platform for developers to rapidly iterate on the software and integrate changes over time. Thus, it speeds up the pre-release testing process, reduces its cost and increases customer satisfaction.

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

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

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

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

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

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

  16. Psychological treatment and therapeutic change in incarcerated rapists

    Directory of Open Access Journals (Sweden)

    Ana Martínez-Catena

    2017-01-01

    Full Text Available Abstract Most Spanish prisons provide specialised treatment for incarcerated sex offenders, both rapists and child molesters. This treatment is a cognitive-behavioural intervention that has shown relative effectiveness in previous research. With regard to offenders’ rehabilitation, recidivism assessments are necessary as a final measure of treatment effectiveness. However, the evaluation of recidivism by itself does not provide sufficient information on the treatment process and the specific effects that treated subjects could undergo. This paper aims to analyse the therapeutic effectiveness of psychological treatment provided to rapists (in general, males sentenced for committing a sexual offence against women. To this aim, a group of treated rapists (N=153 serving a sentence in prison was analysed. Using a specially designed scale (PASSO, the global therapeutic change and ten specific variables (including assertiveness, readiness to change, cognitive distortions, impulsivity, etc. were assessed. The within-subjects comparison showed that treated sex offenders improved, in therapeutic terms, globally as well as in most of the specific variables assessed (improvements not experimented by the control group. Also, different therapeutic subscales showed relevant associations between them. The findings regarding treatment effectiveness are discussed.

  17. Drug activity and therapeutic synergism in cancer treatment.

    Science.gov (United States)

    Carter, W H; Wampler, G L; Stablein, D M; Campbell, E D

    1982-08-01

    In work involving modeling of response surfaces to describe the effects of cancer chemotherapy treatments, it is important to define activity and therapeutic synergism in a statistically defensible manner. This requires the construction of confidence intervals around the estimated optimal treatment which has been achieved by use of an indirect method first proposed by Box and Hunter. Activity for a drug or a combination can be claimed at 100(1 - alpha)% level of confidence when the 100(1 - alpha)% confidence interval about the optimal treatment excludes a zero dose. Results of treatment of B16 melanoma and Lewis lung carcinoma with 3,4-dihydroxybenzohydroxamic acid are used to demonstrate this definition. Extensions of this concept lead to a statistically valid definition of therapeutic synergism. If the confidence region about the optimum combination of k drugs does not contact any of the k - 1 dimensional subspaces, then a k drug therapeutic synergism can be claimed. In the event that a k drug therapeutic synergism cannot be claimed, there may be subsets of the drugs which do combine with therapeutic synergy. These concepts are demonstrated by two- and three-drug combination experiments in L1210-bearing C57BL/6 x DBA/2 F1 (B6D2F1) mice. Razoxane and dacarbazine show therapeutic synergism at a 95% confidence level. A three-drug combination of 5-fluorouracil, Teniposide, and mitomycin C is considered. In this case, although the estimated optimum treatment includes 48.1 mg of 5-fluorouracil per kg, 15.9 mg of Teniposide per kg, and 3.9 mg of mitomycin C per kg, the confidence region generated failed to confirm at an 80% level of confidence that 5-fluorouracil was a necessary component of the best treatment.

  18. Treatment-resistant depression: therapeutic trends, challenges, and future directions

    Directory of Open Access Journals (Sweden)

    Al-Harbi KS

    2012-05-01

    Full Text Available Khalid Saad Al-HarbiMedical College, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi ArabiaBackground: Patients with major depression respond to antidepressant treatment, but 10%–30% of them do not improve or show a partial response coupled with functional impairment, poor quality of life, suicide ideation and attempts, self-injurious behavior, and a high relapse rate. The aim of this paper is to review the therapeutic options for treating resistant major depressive disorder, as well as evaluating further therapeutic options.Methods: In addition to Google Scholar and Quertle searches, a PubMed search using key words was conducted, and relevant articles published in English peer-reviewed journals (1990–2011 were retrieved. Only those papers that directly addressed treatment options for treatment-resistant depression were retained for extensive review.Results: Treatment-resistant depression, a complex clinical problem caused by multiple risk factors, is targeted by integrated therapeutic strategies, which include optimization of medications, a combination of antidepressants, switching of antidepressants, and augmentation with non-antidepressants, psychosocial and cultural therapies, and somatic therapies including electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, deep brain stimulation, transcranial direct current stimulation, and vagus nerve stimulation. As a corollary, more than a third of patients with treatment-resistant depression tend to achieve remission and the rest continue to suffer from residual symptoms. The latter group of patients needs further study to identify the most effective therapeutic modalities. Newer biomarker-based antidepressants and other drugs, together with non-drug strategies, are on the horizon to address further the multiple complex issues of treatment-resistant depression.Conclusion: Treatment

  19. Inhibitor-Based Therapeutics for Treatment of Viral Hepatitis

    Science.gov (United States)

    Dey, Debajit; Banerjee, Manidipa

    2016-01-01

    Abstract Viral hepatitis remains a significant worldwide threat, in spite of the availability of several successful therapeutic and vaccination strategies. Complications associated with acute and chronic infections, such as liver failure, cirrhosis and hepatocellular carcinoma, are the cause of considerable morbidity and mortality. Given the significant burden on the healthcare system caused by viral hepatitis, it is essential that novel, more effective therapeutics be developed. The present review attempts to summarize the current treatments against viral hepatitis, and provides an outline for upcoming, promising new therapeutics. Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail. As such, this review also discusses virally-encoded effectors, found to be essential for virus survival and replication in the host milieu, which may be utilized as potential candidates for development of alternative therapies in the future. PMID:27777893

  20. Host-directed therapeutics as novel angle for tuberculosis treatment.

    Science.gov (United States)

    Kim, Ye-Ram; Yang, Chul-Su

    2017-07-07

    Despite significant efforts to improve tuberculosis (TB) treatment, it remains a worldwide infectious disease due to the limitations of current TB regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors is beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs are more beneficial than existed TB drugs, which are limited the long durations of treatment and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune check points, immune cell functions, and essential enzyme activities. This article includes examples of potentially applicable HDTs and introduces novel approaches for their development.

  1. [Prospective therapeutic trial of masking treatment in patients with tinnitus].

    Science.gov (United States)

    Hernández Moñiz, F; Barrio, A; Pérez, A; Pertierra, M A; Salafranca, J M; González, M

    1998-01-01

    We report the results of a therapeutic trial of patients with tinnitus of different characteristics that was unresponsive to other medical or surgical treatments. Treatment was based on a combination of biofeedback training designed to reduce stress and either pure masking therapy or masking therapy consisting of a hearing aid and masker. The results showed an improvement in subjective perceptions and in the audiometric parameter of pitch in a significant percentage of patients.

  2. Therapeutic Drug Monitoring in the Treatment of Active Tuberculosis

    Directory of Open Access Journals (Sweden)

    Aylin Babalik

    2011-01-01

    Full Text Available Therapeutic drug monitoring ensures optimal dosing while aiming to reduce toxicity. However, due to the high costs and complexity of testing, therapeutic drug monitoring is not routinely used in the treatment of individuals with active tuberculosis, despite the efficacy demonstrated in several randomized trials. This study reviewed data spanning five years regarding the frequency of finding low drug levels in patients with tuberculosis, the dosing adjustments that were required to achieve adequate levels and the factors associated with low drug levels.

  3. The therapeutic alliance in the treatment of personality disorders.

    Science.gov (United States)

    Bender, Donna S

    2005-03-01

    Because personality disorders are associated with significant impairment in interpersonal relationships, special issues and problems arise in the formation of a therapeutic alliance in the treatment of patients with these disorders. In particular, patients with narcissistic, borderline, and paranoid personality traits are likely to have troubled interpersonal attitudes and behaviors that will complicate the patient's engagement with the therapist. While a strong positive therapeutic alliance is predictive of more successful treatment outcomes, strains and ruptures in the alliance may lead to premature termination of treatment. Therefore, clinicians need to consider the patient's characteristic way of relating in order to select appropriate interventions to effectively retain and involve the patient in treatment. Research has shown not only the importance of building an alliance but also that this alliance is vital in the earliest phase of treatment. The author first reviews several definitions of the therapeutic alliance with reference to how they apply to the treatment of patients with personality disorders. Issues relevant to forming a therapeutic alliance with patients with personality disorders are then discussed in terms of the three DSM-IV-TR personality disorder clusters. However, the author notes that these categories do not adequately capture the complexity of character pathology and that clinicians also need to consider which aspects of a patient's personality pathology are dominant at the moment in considering salient elements of the therapeutic alliance. In dealing with Cluster A personality disorders (schizotypal, schizoid, and paranoid personality disorders), what is most relevant for alliance building is the profound impairment in interpersonal relationships. The Cluster B "dramatic" personality disorders (antisocial, borderline, histrionic, and narcissistic) are all associated with pushing the limits. Consequently, clinicians need to exercise great

  4. MicroRNA-targeted therapeutics for lung cancer treatment.

    Science.gov (United States)

    Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

    2017-02-01

    Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

  5. Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Stuart N. Isaacs

    2010-10-01

    Full Text Available Despite the eradication of smallpox several decades ago, variola and monkeypox viruses still have the potential to become significant threats to public health. The current licensed live vaccinia virus-based smallpox vaccine is extremely effective as a prophylactic vaccine to prevent orthopoxvirus infections, but because of safety issues, it is no longer given as a routine vaccine to the general population. In the event of serious human orthopoxvirus infections, it is important to have treatments available for individual patients as well as their close contacts. The smallpox vaccine and vaccinia immune globulin (VIG were used in the past as therapeutics for patients exposed to smallpox. VIG was also used in patients who were at high risk of developing complications from smallpox vaccination. Thus post-exposure vaccination and VIG treatments may again become important therapeutic modalities. This paper summarizes some of the historic use of the smallpox vaccine and immunoglobulins in the post-exposure setting in humans and reviews in detail the newer animal studies that address the use of therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as the development of new therapeutic monoclonal antibodies.

  6. Novel therapeutics for the treatment of metastatic melanoma.

    Science.gov (United States)

    Mansfield, Aaron S; Markovic, Svetomir N

    2009-05-01

    Metastatic malignant melanoma is an incurable disease with a median survival of 8.5 months and a probability of surviving 5 years after the diagnosis of less than 5%. To date, no systemic therapy has meaningfully changed these survival end points. Currently, in the USA the FDA has approved three agents for the treatment of metastatic melanoma: hydroxyurea, dacarbazine and interleukin-2. None of these have demonstrated a meaningfully prolonged survival of patients with metastatic melanoma. Therefore, a number of innovative therapeutic strategies have been pursued to improve outcomes, including immune therapy, tyrosine kinase inhibitors and angiogenesis inhibitors. Herein, we review some of the recent advances in novel therapeutic developments for the treatment of metastatic melanoma.

  7. New therapeutic approaches for treatment of tularaemia: a review

    Directory of Open Access Journals (Sweden)

    Sandrine eBOISSET

    2014-03-01

    Full Text Available Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones, the tetracyclines and the aminoglycosides. Because no effective and safe vaccine is currently available, tularaemia prophylaxis following proven exposure to F. tularensis also relies on administration of antibiotics. A number of reasons make it necessary to search for new therapeutic alternatives: the potential toxicity of first-line drugs, especially in children and pregnant women; a high rate of treatment relapses and failures, especially for severe and/or suppurated forms of the disease; and the possible use of antibiotic-resistant strains in the context of a biological threat. This review presents novel therapeutic approaches that have been explored in recent years to improve tularaemia patients’ management and prognosis. First, the activities of newly available antibiotic compounds were evaluated against F. tularensis, including tigecycline (a glycylcycline, ketolides (telithromycin and cethromycin and fluoroquinolones (moxifloxacin, gatifloxacin, trovafloxacin and grepafloxacin. The liposome delivery of some antibiotics was evaluated. The effect of antimicrobial peptides against F. tularensis was also considered. Other drugs were evaluated for their ability to suppress the intracellular multiplication of F. tularensis. The effects of the modulation of the innate immune response (especially via TLR receptors on the course of F. tularensis infection were characterized. Another approach was the administration of specific antibodies to induce passive resistance to F. tularensis infection. All of these studies highlight the need to develop new therapeutic strategies to improve the management of patients with tularaemia. Many possibilities exist, some unexplored. Moreover, it is likely that new therapeutic alternatives that are effective against this intracellular pathogen could be, at least partially, extrapolated to other human pathogens.

  8. In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins

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    Alina Kurylowicz

    2016-04-01

    Full Text Available Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs, enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs’ expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed.

  9. In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins.

    Science.gov (United States)

    Kurylowicz, Alina

    2016-04-19

    Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs), enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs' expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed.

  10. Therapeutic agents and herbs in topical application for acne treatment.

    Science.gov (United States)

    Kanlayavattanakul, M; Lourith, N

    2011-08-01

    Acne vulgaris suppresses an individual's self-confidence by causing distress with regard to physical appearance, which affects a significant number of individuals during puberty and is delineated by adolescence. Several treatments have been introduced to decrease the aesthetic and psychological problems caused by acne. The topical application of therapeutic agents has been found to be more feasible than hormonal treatment and laser therapy. The ingredients in topical acne treatments, particularly herbs and naturally derived compounds, have received considerable interest as they have fewer adverse effects than synthetic agents. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  11. Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

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    Tiffany M. Mott

    2013-05-01

    Full Text Available Burkholderia mallei, the etiologic agent of glanders, are Category B select agents with biothreat potential, and yet effective therapeutic treatments are lacking. In this study, we showed that CpG administration increased survival, demonstrating protection in the murine glanders model. Bacterial recovery from infected lungs, liver and spleen was significantly reduced in CpG-treated animals as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected animals were infiltrated with higher levels of neutrophils and inflammatory monocytes, as compared to control animals. Employing the B. mallei bioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodal in vivo whole body imaging techniques. CpG-treatment increased recruitment of neutrophils to the lungs and reduced bioluminescent bacteria, correlating with decreased bacterial burden and increased protection against acute murine glanders. Our results indicate that protection of CpG-treated animals was associated with recruitment of neutrophils prior to infection and demonstrated, for the first time, simultaneous real time in vivo imaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimized in vivo imaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections.

  12. Cisplatin encapsulated nanoparticle as a therapeutic agent for anticancer treatment

    Science.gov (United States)

    Eka Putra, Gusti Ngurah Putu; Huang, Leaf; Hsu, Yih-Chih

    2016-03-01

    The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.

  13. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  14. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    Science.gov (United States)

    Klinger, Neil V.

    2016-01-01

    Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

  15. [Nanotechnology offers a promising therapeutic approach for hypertension treatment].

    Science.gov (United States)

    Martín Giménez, V M; Kassuha, D; Manucha, W

    Hypertension is a medical condition considered one of the most important public health problems in developed countries, affecting around one billion people. Therefore, the study of its mechanisms, development and treatment is a priority. Of particular interest are the multiple contributing factors, and efforts by experts to fully understand it are also important. However, studies are currently insufficient and consequently, attention is focused on the exploration of new therapeutic approaches. This raises a growing interest in nanotechnology given the ability of certain structures to mimic the behavior of extracellular matrices. This opens a promising field in the treatment of diseases such as hypertension, where it stands to tissue engineering and its potential applications incorporating concepts such as controlled release drug, reduced side effects and receptor activation locally. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Apoptotic pathways as a therapeutic target for colorectal cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Aman M Abraha; Ezra B Ketema

    2016-01-01

    Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.

  17. Therapeutic treatment of Alzheimer's disease using metal complexing agents.

    Science.gov (United States)

    Price, Katherine A; Crouch, Peter J; White, Anthony R

    2007-11-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by deposition of extracellular amyloid plaques, formation of intracellular neurofibrillary tangles and neuronal dysfunction in the brain. A growing body of evidence indicates a central role for biometals such as copper in many critical aspects of AD. The amyloid beta (Abeta) peptide and its parental molecule, the amyloid precursor protein (APP) both modulate Cu and Zn metabolism in the brain. Therefore, aberrant changes to APP or Abeta metabolism could potentially alter biometal homoestasis in AD, leading to increased free radical production and neuronal oxidative stress. Modulation of metal bioavailability in the brain has been proposed as a potential therapeutic strategy for treatment of AD patients. The lipid permeable metal complexing agent, clioquinol (CQ), has shown promising results in animal models of AD and in small clinical trials involving AD patients. Moreover, a new generation of metal-ligand based therapeutics is currently under development. Patents now cover the generation of novel metal ligand structures designed to modulate metal binding to Abeta and quench metal-mediated free radical generation. However, the mechanism by which CQ and other metal complexing agents slows cognitive decline in AD animal models and patients is unknown. Increasing evidence suggests that ligand-mediated redistribution of metals at a cellular level in the brain may be important. Further research will be necessary to fully understand the complex pathways associated with efficacious metal-based pharmaceuticals for treatment of AD.

  18. Cancer stem cell as therapeutic target for melanoma treatment.

    Science.gov (United States)

    Alamodi, Abdulhadi A; Eshaq, Abdulaziz M; Hassan, Sofie-Yasmin; Al Hmada, Youssef; El Jamal, Siraj M; Fothan, Ahmed M; Arain, Omair M; Hassan, Sarah-Lilly; Haikel, Youssef; Megahed, Mosaad; Hassan, Mohamed

    2016-12-01

    Human malignant melanoma is a highly aggressive skin tumor that is characterized by its extraordinary heterogeneity, propensity for dissemination to distant organs and resistance to cytotoxic agents. Although chemo- and immune-based therapies have been evaluated in clinical trials, most of these therapeutics do not show significant benefit for patients with advanced disease. Treatment failure in melanoma patients is attributed mainly to the development of tumor heterogeneity resulting from the formation of genetically divergent subpopulations. These subpopulations are composed of cancer stem-like cells (CSCs) as a small fraction and non-cancer stem cells that form the majority of the tumor mass. In recent years, CSCs gained more attention and suggested as valuable experimental model system for tumor study. In melanoma, intratumoral heterogeneity, progression and drug resistance result from the unique characteristics of melanoma stem cells (MSCs). These MSCs are characterized by their distinct protein signature and tumor growth-driving pathways, whose activation is mediated by driver mutation-dependent signal. The molecular features of MSCs are either in a causal or consequential relationship to melanoma progression, drug resistance and relapse. Here, we review the current scientific evidence that supports CSC hypothesis and the validity of MSCs-dependent pathways and their key molecules as potential therapeutic target for melanoma treatment.

  19. Inhaled therapeutics for prevention and treatment of pneumonia.

    Science.gov (United States)

    Safdar, Amar; Shelburne, Samuel A; Evans, Scott E; Dickey, Burton F

    2009-07-01

    The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise.

  20. Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment.

    Science.gov (United States)

    Ligabue, Matteo; Lucchetti, Dario; Catone, Tiziana; Fabrizi, Laura; Marvasi, Luigi; Zaghini, Anna; Coni, Ettore

    2005-11-01

    Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits.

  1. MicroRNA as therapeutic targets for treatment of depression

    Directory of Open Access Journals (Sweden)

    Hansen KF

    2013-07-01

    Full Text Available Katelin F Hansen, Karl Obrietan Department of Neuroscience, Ohio State University, Columbus, OH, USA Abstract: Depression is a potentially life-threatening mental disorder affecting approximately 300 million people worldwide. Despite much effort, the molecular underpinnings of clinical depression remain poorly defined, and current treatments carry limited therapeutic efficacy and potentially burdensome side effects. Recently, small noncoding RNA molecules known as microRNA (miRNA have gained prominence as a target for therapeutic intervention, given their capacity to regulate neuronal physiology. Further, mounting evidence suggests a prominent role for miRNA in depressive molecular signaling. Recent studies have demonstrated that dysregulation of miRNA expression occurs in animal models of depression, and in the post-mortem tissue of clinically depressed patients. Investigations into depression-associated miRNA disruption reveals dramatic effects on downstream targets, many of which are thought to contribute to depressive symptoms. Furthermore, selective serotonin reuptake inhibitors, as well as other antidepressant drugs, have the capacity to reverse aberrant depressive miRNA expression and their downstream targets. Given the powerful effects that miRNA have on the central nervous system transcriptome, and the aforementioned studies, there is a compelling rationale to begin to assess the potential contribution of miRNA to depressive etiology. Here, we review the molecular biology of miRNA, our current understanding of miRNA in relation to clinical depression, and the utility of targeting miRNA for antidepressant treatment. Keywords: depression, microRNA, miRNA, BDNF, Dicer, serotonin

  2. Modern opportunities of therapeutic treatment of allergic conjunctivitis. A review

    Directory of Open Access Journals (Sweden)

    D. Yu. Maychuk

    2014-07-01

    Full Text Available H1‑receptor antagonists are drugs of choice to treat allergy. They work very fast as their therapeutic effect develops within 10‑15 min, have good tolerability and almost no adverse side-effects, and require no frequent instillations. Levocabastine quickly inhibits allergic reaction caused by specific allergen or histamine. Levocabastine while being a highly-selective H1‑receptor antagonist is the most perspective topical mono-drug used to treat acute allergic conjunctivitis. Levocabastine applied on a spot produces instant effect which persists for a long time so that instillations twice a day (BID are enough. Levocabastine is more effective than other 15 antihistamines. In contrast to previous antihistamines, levocabastine blocks vasodilatation and reduces vascular permeability increase. Levocabastine eye drops have good tolerability comparable with cromoglicic acid eye drops and placebo. Levocabas tine is successfully used in allergic conjunctivitis (pollinosis, perennial, vernal, rhinoconjunctivitis treatment in children. Its efficacy is the same or even higher than that of cromoglycate and azelastine. 20 clinical studies (more than 1200 patients revealed that levocabastine eye drops are effective, work quickly and have good tolerability. This drug is efficient in allergic conjunctivitis treatment and acute infectious conjunctivitis complex therapy. 

  3. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

    Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

  4. Measuring Therapeutic Alliance with Children in Residential Treatment and Therapeutic Day Care

    Science.gov (United States)

    Roest, Jesse; van der Helm, Peer; Strijbosch, Eefje; van Brandenburg, Mariëtte; Stams, Geert Jan

    2016-01-01

    Purpose: This study examined the construct validity and reliability of a therapeutic alliance measure (Children's Alliance Questionnaire [CAQ]) for children with psychosocial and/or behavioral problems, receiving therapeutic residential care or day care in the Netherlands. Methods: Confirmatory factor analysis of a one-factor model ''therapeutic…

  5. Acupuncture as a therapeutic treatment option for threatened miscarriage

    Directory of Open Access Journals (Sweden)

    Betts Debra

    2012-03-01

    Full Text Available Abstract Background Threatened miscarriage involves vaginal bleeding in a pregnancy that remains viable. This is a common early pregnancy complication with increased risk factors for early pregnancy loss, preterm premature rupture of membranes (PPROM, preterm delivery, low birth weight babies and maternal antepartum haemorrhage. Currently there are no recommended medical treatment options, rather women receive advice that centres on a 'wait and see' approach. For women with a history of unexplained recurrent miscarriage providing supportive care in a subsequent pregnancy improves live birthing outcomes, but the provision of supportive care to women experiencing threatened miscarriage has to date not been examined. Discussion While it is known that 50-70% of miscarriages occur due to chromosomal abnormalities, the potential for therapeutic intervention amongst the remaining percentage of women remains unknown. Complementary and alternative medicine (CAM therapies have the potential to provide supportive care for women presenting with threatened miscarriage. Within fertility research, acupuncture demonstrates beneficial hormonal responses with decreased miscarriage rates, raising the possibility acupuncture may promote specific beneficial effects in early pregnancy. With the lack of current medical options for women presenting with threatened miscarriage it is timely to examine the possible treatment benefits of providing CAM therapies such as acupuncture. Summary Despite vaginal bleeding being a common complication of early pregnancy there is often reluctance from practitioners to discuss with women and medical personal how and why CAM may be beneficial. In this debate article, the physiological processes of early pregnancy together with the concept of providing supportive care and acupuncture are examined. The aim is to raise awareness and promote discussion as to the beneficial role CAM may have for women presenting with threatened miscarriage.

  6. A Novel Therapeutic for the Treatment and Prevention of Hearing Loss from Acoustic Trauma

    Science.gov (United States)

    2015-05-01

    Award Number: W81XWH-14-1-0077 TITLE: A NOVEL THERAPEUTIC FOR THE TREATMENT AND PREVENTION OF HEARING LOSS FROM ACOUSTIC TRAUMA PRINCIPAL...2015 4. TITLE AND SUBTITLE A Novel Therapeutic for the Treatment and Prevention of Hearing Sa. CONTRACT NUMBER: Loss from Acoustic Trauma WB l XW...Quad Chart is submitted as an appendix. 9. APPENDICES Quad Chart 6 A Novel Therapeutic for the Treatment and Prevention of Hearing Loss from

  7. Correlates of Therapeutic Alliance and Treatment Outcomes among Israeli Female Methadone Patients

    Science.gov (United States)

    Schiff, Miriam; Levit, Shabtay

    2010-01-01

    Objectives: This study examines potential predictors (e.g., attachment style, frequency of therapeutic treatment sessions) of client-rated therapeutic alliance between the social worker and client. The relationship between therapeutic alliance and client's psychological outcomes (hope and posttraumatic stress symptoms [PTS's]) was also assessed.…

  8. Therapeutic gymnastics in comprehensive treatment of patients with generalized myasthenia

    Science.gov (United States)

    Kapelovich, R. L.

    1980-01-01

    The technique of therapeutic gymnastics was used for patients with mayasthenia gravis to control the consequences of hypodynamia induced by the myasthenic process. It is concluded that during myasthenia, the severity of the disease is due to the affection of the cross striated musculature. The most life threatening are the disorders in respiration and swallowing, that can be intensified by forced stay in bed and immobility. It is also concluded that the use of therapeutic gymnastics in patients which myasthenia promotes efficient presurgical preparation, and in the post surgical period; prevention of pulmonary complications and normalization of respiration. Therapeutic gymnastics with regard to the severity and localization of the myasthenic disorders must be a component part of the presurgical preparation and postsurgical management of patients with generalized myasthenia.

  9. [Therapeutic bronchoscopic treatment of postintubation tracheal stenosis: 5 cases].

    Science.gov (United States)

    Karakoca, Yalçin; Karaağaç, Güler; Karakoca, Sevinay; Yildiz, Tülay; Yazanel, Orhan; Sariman, Nesrin; Yildiz, M Erdem; Tekinsoy, Bülent

    2004-01-01

    Benign airway obstruction is known as curable by therapeutic bronchoscopic methods. Compared by surgical therapies it is comfortable and has no risks for the patients. For five patients who applied our clinic after tracheostomy and endotracheal intubation stenosis we used therapeutic bronchoscopic methods; "laser-stenotic silicon stent". In two patients after vaporization of membranous stricture by Neodimum Yttrium Aliminum Pevroskite Laser (Nd-YAP laser) who were seen posttracheostomy and postentubation; stenotic stent was implanted mechanically and/or by means of baloon dilatation. Membranous stricture area was coagulated by Nd-YAP-laser in other three cases and anatomic airway diameter was achieved mechanically and by baloon dilatation. In the follow up period we applied stenotic silicon stent implantation after second laser resection in whom restenosis observed. In conclusion; patients who had stenotic silicon stent implantation and having no problems in the follow up this therapeutic method is found to be curative.

  10. FGFR-targeted therapeutics for the treatment of breast cancer.

    Science.gov (United States)

    De Luca, Antonella; Frezzetti, Daniela; Gallo, Marianna; Normanno, Nicola

    2017-03-01

    Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients. Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed. Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

  11. Therapeutic chemical treatment of grape vines for root diseases

    Science.gov (United States)

    There is a need to develop post-plant treatment of soil pests for perennial vine and tree crops. Field trials were performed to evaluate post-plant treatment of established grape vines (Vitis vinifera var. Thompson Seedless) with known problems of soilborne plant-parasitic nematodes and pathogens us...

  12. Plant Alkaloids as an Emerging Therapeutic Alternative for the Treatment of Depression

    OpenAIRE

    Sadia ePervez; Haroon eKhan; Aini eKhan

    2016-01-01

    Depression is a heterogeneous mood disorder that has been classified and treated in a variety of ways. Although, a number of synthetic drugs are being used as standard treatment for clinically depressed patients, but they have adverse effects that can compromise the therapeutic treatments and patient's compliance. Unlike, synthetic medications, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy associated with least side effects, which i...

  13. Therapeutic Effect Observations on Individualized Treatment of Peripheral Facial Palsy

    Institute of Scientific and Technical Information of China (English)

    何希俊; 谭吉林; 王本国; 郭瑞兰; 韩丑萍

    2006-01-01

    目的:观察采用个体化方案治疗周围性面瘫的疗效.方法:治疗组121例患者根据其病情特点采用个体化方案进行针刺治疗,与118例常规针灸治疗者进行对照研究,比较其疗程与疗效的差异.结果:治疗组愈显率为90.9%,对照组愈显率为69.5%,差异有显著性(P<0.01);两组各疗程愈显率比较,差异有显著性(P<0.01).结论:采用个体化方案治疗周围性面瘫效果明显优于常规针刺方法,且疗程短.%To investigate the curative effect of individualized treatment on peripheral facial paralysis. Methods:A treatment group of 121 patients was treated with acupuncture under an individualized plan based on the condition of disease. For a control study,118 patients were treated with conventional acupuncture. The courses of treatment and the curative effects were compared. Results:The cure and marked efficacy rate was 90.9% in the treatment group and 69.5% in the control group. There was a significant difference (P<0.01).There was also a significant difference in the cure and marked efficacy rate in each courses of treatment between the two groups (P<0.01). Conclusion:Individualized acupuncture treatment is better in the effect and shorter in the courses than conventional acupuncture treatment for peripheral facial paralysis.

  14. Gene therapy as a therapeutic approach for the treatment of rheumatoid arthritis: innovative vectors and therapeutic genes.

    Science.gov (United States)

    Adriaansen, J; Vervoordeldonk, M J B M; Tak, P P

    2006-06-01

    In recent years, significant progress has been made in the treatment of rheumatoid arthritis (RA). In addition to conventional therapy, novel biologicals targeting tumour necrosis factor-alpha have successfully entered the clinic. However, the majority of the patients still has some actively inflamed joints and some patients suffer from side-effects associated with the high systemic dosages needed to achieve therapeutic levels in the joints. In addition, due to of the short half-life of these proteins there is a need for continuous, multiple injections of the recombinant protein. An alternative approach might be the use of gene transfer to deliver therapeutic genes locally at the site of inflammation. Several viral and non-viral vectors are being used in animal models of RA. The first gene therapy trials for RA have already entered the clinic. New vectors inducing long-term and regulated gene expression in specific tissue are under development, resulting in more efficient gene transfer, for example by using distinct serotypes of viral vectors such as adeno-associated virus. This review gives an overview of some promising vectors used in RA research. Furthermore, several therapeutic genes are discussed that could be used for gene therapy in RA patients.

  15. Emerging therapeutics for the treatment of diabetic nephropathy.

    Science.gov (United States)

    Brenneman, Jehrod; Hill, Jon; Pullen, Steve

    2016-09-15

    Diabetic nephropathy (DN) is the most common pathology contributing to the development of chronic kidney disease (CKD). DN caused by hypertension and unmitigated inflammation in diabetics, renders the kidneys unable to perform normally, and leads to renal fibrosis and organ failure. The increasing global prevalence of DN has been directly attributed to rising incidences of Type II diabetes, and is now the largest non-communicable cause of death worldwide. Despite the high morbidity, successful new treatments for DN are lacking. This review seeks to provide new insight on emerging clinical candidates under investigation for the treatment of DN.

  16. Therapeutic Application of Natural Medicine Monomers in Cancer Treatment.

    Science.gov (United States)

    Zhong, Chen; Wall, Nathan R; Zu, Yuangang; Sui, Guangchao

    2017-07-14

    Natural medicine monomers (NMMs) isolated from plants have been recognized for their roles in treating different human diseases including cancers. Many NMMs exhibit effective anti-cancer activities and can be used as drugs or adjuvant agents to enhance the efficacy of chemotherapy and radiotherapy with low or tolerable side effects. Some NMMs, such as Paclitaxel and Camptothecin, have been extensively studied for decades and are now used as anti-cancer medicines due to their remarkable curative effects, such as inhibiting cancer cell proliferation and metastasis, and inducing cell death and differentiation. Although therapeutic effects for most NMMs have been appreciated, the underlying mechanisms of their anti-cancer activities remain largely unexplored. In this review, we have grouped NMMs into six categories based on their chemical structures, and summarized current knowledge of molecular mechanisms of anti-cancer activities to provide a theoretical basis for clinical application and new drug development of NMMs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. [Molecular therapeutics in patients with cancer unresponsive to conventional treatments].

    Science.gov (United States)

    Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Víctor Edmundo

    2008-01-01

    Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of molecularly target-therapeutic (MTT) strategies. Cancer is a complex process due to accumulation of multiple mutations and alterations in the genoma. Tumor cells seem to rely heavily on the continued deregulation of one or more signaling pathways. Complete identification on cell signaling deregulations have provided greater understanding on the biology that underlies most cancers. High-throughput technologies in genomics and proteomics can help to detect the response in vitro and in vivo of targeted MTT effects. Cancer MTT are drugs blocking specific oncogenes or oncogenic signaling pathways and can secondary block off the growth and spreading involved in carcinogenesis and tumor progression. In this paper we revised concepts of oncogene addiction, oncogenic pathways signature and commented the high-tech technologies related to their study. Also we revised the favorable clinical results using new MTT strategies for hard-to-treat cancers in the last year, and the limitations and perspectives to achieve more effective targeted cancer therapy results. Identification of a progressive number of molecularly targeted oncogenes and their corresponding blocking agents will give cancer MTT strategies great potential for development in the next years. Novel biologic endpoints and innovative clinical designs are also required to the successful application of the therapies.

  18. OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE IN THE TREATMENT OF POSTOPERATIVE HEMIPLEGIA

    Institute of Scientific and Technical Information of China (English)

    包飞; 张云祥

    2004-01-01

    Objective: To observe the therapeutic effect of acupuncture in the treatment of hemiplegia resulted from craniocerebral operation. Methods: A total of 40 cases of postoperative hemiplegia patients were randomly and evenly divided into treatment group and control group that were respectively treated with acupuncture plus conventional therapy (anti-inflammation, intracranial pressure-lowering and alimentotherapy) and conventional therapy. Results: After treatment, the therapeutic effect for raising myodynamia of the paralyzed limbs in treatment group was significantly superior to that of control group (upper limb P<0.01, and lower limb P<0.05). Conclusion: Acupuncture can effectively facilitate the recovery of the paralyzed limb in patients undergoing cerebral surgical operation.

  19. Therapeutic Factors in Spouse-Abuse Group Treatment.

    Science.gov (United States)

    Schwartz, Jonathan P.; Waldo, Michael

    1999-01-01

    Examines men's experiences in educational groups for batterers. Two factors, imparting of information and development of socializing techniques, were found to be predominant. Other factors thought to be important for abuse treatment (i.e. hope, family reenactment, and modeling) were found to be minimally present. Analysis demonstrates relationship…

  20. Therapeutic Treatment Protocol for Enuresis Using an Enuresis Alarm

    Science.gov (United States)

    Shapira, Bettina E.; Dahlen, Penny

    2010-01-01

    Enuresis, one of the most prevalent and chronic childhood disorders, imposes serious financial, physical, and emotional burdens on the child and the family affected by it. This article provides counselors with an overview of the complex etiologies, diagnostic criteria, and current treatment options for the disorder, as well as assessment tools and…

  1. Cyclotherapy: opening a therapeutic window in cancer treatment.

    Science.gov (United States)

    van Leeuwen, Ingeborg M M

    2012-06-01

    Cyclotherapy is a promising endeavor to improve cancer treatment by tackling the dose-limiting side effects of chemotherapy, especially for cancers harboring mutations in the TP53 tumor suppressor. In this particular context, pretreatment with a p53 activator halts proliferation in healthy tissue, while leaving the p53-deficient tumor susceptible to conventional chemotherapy.

  2. The Effects of Feeding Unpredictability and Classical Conditioning on Pre-Release Training of White-Lipped Peccary (Mammalia, Tayassuidae)

    Science.gov (United States)

    Nogueira, Selene S. C.; Abreu, Shauana A.; Peregrino, Helderes; Nogueira-Filho, Sérgio L. G.

    2014-01-01

    Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari), a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3) and unpredictable feeding phases (U1- signaled and U2- non-signaled). The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2) than during the other two predictable phases (C1 and C3). The peccaries also spent less time feeding during the signaled unpredictable phase (U1) and the following control phase (C2) than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2), also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild. PMID:24475072

  3. The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae.

    Directory of Open Access Journals (Sweden)

    Selene S C Nogueira

    Full Text Available Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari, a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3 and unpredictable feeding phases (U1- signaled and U2- non-signaled. The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2 than during the other two predictable phases (C1 and C3. The peccaries also spent less time feeding during the signaled unpredictable phase (U1 and the following control phase (C2 than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2, also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

  4. [Therapeutic concepts in the treatment of postmenopausal osteoporosis].

    Science.gov (United States)

    Leidig-Bruckner, G; Ziegler, R

    1994-11-01

    Postmenopausal osteoporosis is not a well-defined disease, but summarizes women with different severity of changes in bone metabolism and different clinical complaints. The only common feature in women with 'postmenopausal osteoporosis' is the deficiency of estrogen. Postmenopausal women can be subdivided into four groups, according to their risk for fractures: 1. women without evident increase of fracture risk (bone mineral content between 0 and 2 SD of age-related normal range, no known risk factors from history); 2. women with possible increase of fracture risk (bone mineral content between 0 and -2 SD of age-related normal range, with or without known risk factors from history); 3. women with clear increase of fracture risk (bone mineral content below age-related normal range, with or without known risk factors from history); 4. women with already occurred fracture (manifest osteoporosis). Therapeutic intervention in postmenopausal women should be adapted to the risk for fracture. In all four groups a secondary prevention or basic therapy should be performed, focusing on calcium intake, vitamin D supply and sufficient physical activity. Calcium intake should be 1500 mg/day in women without estrogen substitution and 1000 mg in women with estrogen substitution. In patients living mainly inside or with malnutrition, a daily substitution of 500 E. Vitamin D3 is recommended. In group 2, regular control of bone mass is recommended to start additional estrogen replacement therapy, if accelerated loss of bone mass occurs. In group 3, estrogen replacement therapy is recommended urgently and is the therapy of first choice to prevent development of fractures. In group 4 (manifest osteoporosis), therapy should aim on improvement of the patient's symptoms and on increase of bone stability to avoid further fractures. The symptomatic therapy includes pain medications and an intensive physical therapy adapted to the patient's needs. Physical therapy should be performed for

  5. Novel therapeutic agents in the treatment of metastaticcolorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Over the past couple of decades considerable progresshas been made in the management of metastaticcolorectal cancers (mCRC) leading to a significant improvementin five-year survival. Although part of thissuccess has been rightly attributed to aggressive surgicalmanagement and advances in other adjunct treatments,our understanding of the pathogenesis of cancer andemergence of newer molecular targets for colon cancerhas created a powerful impact. In this review article wewill discuss various targeted therapies in the managementof mCRC. Newer agents on the horizon soon to beincorporated in clinical practice will be briefly reviewedas well.

  6. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment

    Science.gov (United States)

    Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Abad, Sonia; Sánchez-López, Elena; García, M. Luisa; Olloquequi, Jordi; Beas-Zarate, Carlos; Auladell, Carme; Camins, Antoni

    2016-01-01

    Alzheimer's disease (AD) currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ) peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a) to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b) to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR) activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC). PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5). Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease. PMID:26881137

  7. Mangiferin: A promising therapeutic agent for rheumatoid arthritis treatment.

    Science.gov (United States)

    Luczkiewicz, P; Kokotkiewicz, A; Dampc, A; Luczkiewicz, M

    2014-11-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Despite aggressive treatment with anti-rheumatic drugs, progressive destruction of joints continues to occur in RA patients, who subsequently require joint surgery. A lot of evidence suggest that fibroblast-like synovial cells (FLS) play crucial role in joint degradation and the propagation of inflammation in RA. The expansion of fibroblast populations in the joint results primarily from the inhibition of pro-apoptotic pathways, rather than large scale proliferation. Because multiple factors, which contribute to fibroblast activation and enhance their destructive potential, are under control of transcription factor NF-κB, this pathway presents an interesting target for RA therapy. However, due to the lack of specificity, NF-κB inhibitors may exert severe side effects. Given the above, there has recently been more interest in natural substances of plant origin which are regarded as a safe alternatives for synthetic drugs. Mangiferin, the naturally occurring polyphenol with excellent anti-inflammatory and antioxidative properties, exhibits strong pro-apoptotic effect toward synoviocytes isolated from human synovia. Moreover, it shows no cytotoxicity toward cultivated chondrocytes and reduces the levels of matrix metalloproteinases. Considering that mangiferin is a natural constituent of foods and traditional herbal medicines, showing fewer adverse effects and low toxicity, we hypothesize that it may prove effective in the treatment of RA and prevention against joint destruction.

  8. Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment

    Directory of Open Access Journals (Sweden)

    Jaume Folch

    2016-01-01

    Full Text Available Alzheimer’s disease (AD currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC. PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5. Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease.

  9. Therapeutic potential of octreotide in the treatment of liver metastases.

    Science.gov (United States)

    Davies, N; Cooke, T G; Jenkins, S A

    1996-01-01

    Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.

  10. [Therapeutic utility of biguanides in the treatment of NIDDM].

    Science.gov (United States)

    Fujimoto, S

    1999-03-01

    Metformin, one of the biguanides, is an oral hypoglycemic agent which acts primarily by decreasing hepatic glucose output and by increasing peripheral glucose disposal, therefore it has different hypoglycemic mechanism from that of sulfonylureas. The hypoglycemic effects of metformin are observed not only in obese NIDDM patients, but also in non-obese NIDDM patients. Moreover, addition of metformin improves glycemic control in patients with suboptimal glycemic control while taking maximum sulfonylurea therapy. Therefore, it is complementary to sulfonylurea therapy and represents a useful additional drug for the treatment, irrespective of obesity. The rare but serious condition of lactic acidosis should be kept in mind as a potential side effect, however, if metformin is avoided in patients with contraindications, the medication is very safe.

  11. Plant-derived therapeutics for the treatment of metabolic syndrome.

    Science.gov (United States)

    Graf, Brittany L; Raskin, Ilya; Cefalu, William T; Ribnicky, David M

    2010-10-01

    Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual's likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints. This review assesses examples of commonly known and partially characterized botanicals to describe specific considerations for the phytochemical, preclinical and clinical characterization of botanicals associated with metabolic syndrome.

  12. Analysis on Therapeutic Features of Ancient Acupuncture Treatment for Impotence

    Institute of Scientific and Technical Information of China (English)

    刘立公; 顾杰

    2009-01-01

    To analyze the acupuncture treatment for impotence in 130 kinds of classical medical books by computer,and summarize the rules of acupuncture for this disease.The results showed that selection of acupoints along the meridians,selection of acupoints by boay parts,selection ofacupoints by pattern identification are the laws ofacupuncture for this disease.%运用计算机对130种古医籍中用针灸治疗阳痿的内容进行分析,总结古代医家针灸治疗本病的用穴规律.结果发现针灸治疗本病有循经取穴,分部取穴和辨证取穴特点.

  13. Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic regimen.

    Science.gov (United States)

    Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D; Van Nostrand, Douglas; Wartofsky, Leonard

    2011-01-01

    The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3-0.5% and 2-3%, respectively. Thyroid autoantibodies are found in 5-18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy.

  14. Levothyroxine Treatment in Pregnancy: Indications, Efficacy, and Therapeutic Regimen

    Directory of Open Access Journals (Sweden)

    Joanna Klubo-Gwiezdzinska

    2011-01-01

    Full Text Available The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3–0.5% and 2–3%, respectively. Thyroid autoantibodies are found in 5–18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy.

  15. The role of expectation in the therapeutic outcomes of alcohol and drug addiction treatments.

    Science.gov (United States)

    Spagnolo, Primavera A; Colloca, Luana; Heilig, Markus

    2015-05-01

    Throughout history, patient-physician relationships have been acknowledged as an important component of the therapeutic effects of any pharmacological treatment. Here, we discuss the role of physicians' expectations in influencing the therapeutic outcomes of alcohol and drug addiction pharmacological treatments. As largely demonstrated, such expectations and attitudes may contribute to produce placebo and nocebo effects that in turn affect the course of the disease and the response to the therapy. This article is aimed at discussing the current insights into expectations, placebo and nocebo mechanisms and their impact on the therapeutic outcomes of alcohol and drug addiction treatments; with the goal of informing physicians and other health care providers about the potentially widespread implications for clinical practice and for a successful treatment regimen. Published by Oxford University Press on behalf of Medical Council on Alcohol 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Dutch guidance for the treatment of chronic hepatitis C virus infection in a new therapeutic era

    NARCIS (Netherlands)

    Berden, F.A.C.; Kievit, W.; Baak, L.C.; Bakker, C.M.; Beuers, U.; Boucher, C.A.B.; Brouwer, J.T.; Burger, D.M.; Erpecum, K.J. van; Hoek, B. van; Hoepelman, A.I.; Honkoop, P.; Kerbert-Dreteler, M.J.; Knegt, R.J. de; Koek, G.H.; Nieuwkerk, C.M. van; Soest, H. van; Tan, A.C.; Vrolijk, J.M.; Drenth, J.P.H.

    2014-01-01

    BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval

  17. Changes in Personality Disorder Traits Following 2 Years of Treatment in a Secure Therapeutic Community Milieu

    Science.gov (United States)

    Morrissey, Catrin; Taylor, Jon

    2014-01-01

    Therapeutic community treatment models have not previously been applied to forensic patients with mild intellectual disabilities (IDs) with a comorbid diagnosis of personality disorder. Thirteen patients with mild IDs were allocated to a unit within a high secure psychiatric service operating a model of treatment based on the principles and…

  18. Problem Severity Profiles of Substance Abusing Women in Therapeutic Treatment Facilities

    Science.gov (United States)

    Isralowitz, Richard; Reznik, Alexander

    2009-01-01

    This article aims to examine specific substance use profiles among former Soviet Union (FSU) immigrant and native-born women in Israeli therapeutic treatment facilities. Individuals were sampled at drug treatment facilities and assessed using the Addiction Severity Index. ASI scores suggest differences between the two groups. Among the findings…

  19. The therapeutic community as an adaptable treatment modality across different settings.

    Science.gov (United States)

    Kennard, David

    2004-01-01

    Simple core statements of the therapeutic community as a treatment modality are given, including a "living-learning situation" and "culture of enquiry." Applications are described in work with children and adolescents, chronic and acute psychoses, offenders, and learning disabilities. In each area the evolution of different therapeutic community models is outlined. In work with young people the work of Homer Lane and David Wills is highlighted. For long term psychosis services, the early influence of "moral treatment" is linked to the revitalisation of asylums and the creation of community based facilities; acute psychosis services have been have been run as therapeutic communities in both hospital wards and as alternatives to hospitalisation. Applications in prison are illustrated through an account of Grendon prison. The paper also outlines the geographical spread of therapeutic communities across many countries.

  20. OBSERVATION ON THE THERAPEUTIC EFFECT OF CT-AIDED SURROUNDING NEEDLING TREATMENT OF ISCHEMIC STROKE

    Institute of Scientific and Technical Information of China (English)

    PAN Wenyu; LI Yanhui; LIN Guohua

    2002-01-01

    121 cases of ischemic stroke were randomly divided into CT-aided surrounding needling group (CTASN, 61 cases) and scalp Acupuncture group (SA, 60 cases). After 30 sessions of treatment the therapeutic results of the two groups are significantly different (P < 0.05), the therapeutic effect of CTASN group is better than that of SA group. The plasma contents of TXB2 and 6-keto-PGF1a of the two groups change considerably after acupuncture treatment, the change in CTASN group is more obvious.

  1. OBSERVATION ON THE THERAPEUTIC EFFECT OF CT—AIDED SURROUNDING NEEDLING TREATMENT OF ISCHEMIC STROKE

    Institute of Scientific and Technical Information of China (English)

    潘文宇; 李艳慧; 等

    2002-01-01

    121 Cases of ischemic stroke were randomly divided into CT-aided surrounding needling group(CTASN,61 cases)and scalp Acupuncture group(SA,60 cases),After 30 sessions of treatment the therapeutic results of the two groups are significantly different (P<0.05),the therapeutic effect of CTANS group is better than than of SA group.The plasma contents of TXB2 and 6-keto-PGF1a of the two groups change considerably after acupuncture treatment,the change in CTASN group is more obvious.

  2. Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Yilong Zhang

    2015-03-01

    Full Text Available The hepatocyte growth factor (HGF: MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.

  3. The effect of treatment history on therapeutic outcome: psychological and neurobiological underpinnings.

    Directory of Open Access Journals (Sweden)

    Simon Kessner

    Full Text Available It is increasingly recognized that the efficacy of medical treatments is determined in critical part by the therapeutic context in which it is delivered. An important characteristic of that context is treatment history. We recently reported first evidence for a carry-over of treatment experience to subsequent treatment response across different treatment approaches. Here we expand on these findings by exploring the psychological and neurobiological underpinnings of the effect of treatment experience on future treatment response in an experimental model of placebo analgesia with a conditioning procedure. In a combined behavioral and neuroimaging study we experimentally induced positive or negative experiences with an analgesic treatment in two groups of healthy human subjects. Subsequently we compared responses to a second, different analgesic treatment between both groups. We found that participants with an experimentally induced negative experience with the first treatment showed a substantially reduced response to a second analgesic treatment. Intriguingly, several psychological trait variables including anxiety, depression and locus of control modulate the susceptibility for the effects of prior treatment experiences on future treatment outcome. These behavioral effects were supported by neuroimaging data which showed significant differences in brain regions encoding pain and analgesia between groups. These differences in activation patterns were present not only during the pain phase, but also already prior to painful stimulation and scaled with the individual treatment response. Our data provide behavioral and neurobiological evidence showing that the influence of treatment history transfers over time and over therapeutic approaches. Our experimental findings emphasize the careful consideration of treatment history and a strictly systematic treatment approach to avoid negative carry-over effects.

  4. CLINICAL OBSERVATION ON THERAPEUTIC EFFECTS OF COMBINED TREATMENT OF NONINSULIN DEPENDENT DIABETES

    Institute of Scientific and Technical Information of China (English)

    ZHU Jin-gui; QU Hui-qing

    2005-01-01

    Objective: To observe the therapeutic effect of combined treatment of diabetes mellitus (DM) and its complications. Methods: 30 cases of noninsulin dependent diabetes were treated by electroacupuncture (EA)of Tianzhu (天柱 BL 10), Dashu (大杼 BL 11), Fengmen (风门 BL 12), Jueyinshu (厥阴俞 BL 14), etc, massage at the acupoints along the Bladder Meridian, point injection of Vitamin B1, B6, B12 plus lidocaine at Neiguan (内关 PC 6) and Sanyinjiao (三阴交 SP 6, once every 3 days), cupping and physiotherapy comprehensively. The therapeutic effect was analyzed after 40 treatments. Results: After treatment, of the 30 cases, 23 (76.7%) experienced remarkable improvement in their symptoms and the rest 7 (23.3%) had improvement, with the total effective rate being 100%. Conclusion: The abovementioned combined treatment method works well in improving clinical symptoms of type Ⅱ DM patients.

  5. Early Therapeutic Alliance and Treatment Outcome in Individual and Family Therapy for Adolescent Behavior Problems

    Science.gov (United States)

    Hogue, Aaron; Dauber, Sarah; Stambaugh, Leyla Faw; Cecero, John J.; Liddle, Howard A.

    2006-01-01

    The impact of early therapeutic alliance was examined in 100 clients receiving either individual cognitive-behavioral therapy (CBT) or family therapy for adolescent substance abuse. Observational ratings of adolescent alliance in CBT and adolescent and parent alliance in family therapy were used to predict treatment retention (in CBT only) and…

  6. Modified Therapeutic Community Treatment for Offenders with Co-Occurring Disorders: Mental Health Outcomes

    Science.gov (United States)

    Sullivan, Christopher J.; Sacks, Stanley; McKendrick, Karen; Banks, Steven; Sacks, Joann Y.; Stommel, Joseph

    2007-01-01

    This paper examines outcomes 12 months post-prison release for offenders with co-occurring disorders (n = 185) randomly assigned to either a mental health control treatment (C) or a modified therapeutic community (E). Significant between-group differences were not found for mental health measures, although improvements were observed for each…

  7. Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

    NARCIS (Netherlands)

    Zuur, Marlanka A.; Bolhuis, Mathieu S.; Anthony, Richard; den Hertog, Alice; van der Laan, Tridia; Wilffert, Bob; Lange, de Wiel; van Soolingen, Dick; Alffenaar, Jan-Willem C.

    Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order

  8. Methadone: The Drug and Its Therapeutic Uses In the Treatment of Addiction. Series 31, No. 1.

    Science.gov (United States)

    Gamage, James R.; Zerkin, E. Lief

    This fact sheet from the National Clearinghouse for Drug Abuse Information discusses methadone, a therapeutic drug for the treatment of narcotic addiction. It reviews the pharmacology of the drug as well as physiological and psychological effects, patterns of use, and adverse effects (toxicity and poisoning). It examines the success rates of…

  9. The Relationship of Perfectionism, Depression, and Therapeutic Alliance during Treatment for Depression: Latent Difference Score Analysis

    Science.gov (United States)

    Hawley, Lance L.; Ho, Moon-Ho Ringo; Zuroff, David C.; Blatt, Sidney J.

    2006-01-01

    The authors examined the longitudinal relationship of patient-rated perfectionism, clinician-rated depression, and observer-rated therapeutic alliance using the latent difference score (LDS) analytic framework. Outpatients involved in the Treatment for Depression Collaborative Research Program completed measures of perfectionism and depression at…

  10. The impact of the therapeutic alliance on treatment outcome in patients with dissociative disorders

    Science.gov (United States)

    Cronin, Elisabeth; Brand, Bethany L.; Mattanah, Jonathan F.

    2014-01-01

    Background Research has shown that the therapeutic alliance plays an important role in enhancing treatment outcome among individuals with a variety of disorders, including posttraumatic stress disorder (PTSD). However, the therapeutic alliance and treatment outcome has not yet been studied in dissociative disorders (DD). Objectives The current study sought to investigate the impact of alliance on treatment outcome for DD patients. Methods Data from a naturalistic, longitudinal international treatment study of DD patients and their therapists were analyzed to determine if the alliance, as reported by patients and therapists, was associated with treatment outcome. Results Patients with higher self-rated alliance had fewer symptoms of dissociation, PTSD, and general distress, as well as higher levels of therapist-rated adaptive functioning. Over time, self-rated alliance scores predicted better outcomes, after controlling for patient adaptive capacities including symptom management at the time when the alliance ratings were made. Patient-rated alliance was more strongly associated with outcome than therapist-rated alliance. Conclusion Therapists who work with DD patients should understand the importance of the alliance on treatment outcome. These findings are consistent with previous literature demonstrating the importance of developing and maintaining a strong therapeutic alliance, although the effect sizes of individuals with DD were stronger than what has been found in many other patient groups. A greater understanding of the impact of the alliance in traumatized individuals may contribute to better outcomes for these individuals. PMID:24616755

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

    Directory of Open Access Journals (Sweden)

    Basanti Jena

    2013-12-01

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

  12. OBSERVATION ON THE THERAPEUTIC EFFECT OF AURICULAR PLASTER FOR TREATMENT OF 135 CASES OF MOTION SICKNESS

    Institute of Scientific and Technical Information of China (English)

    RAO Zhongdong; WEN Ming; HU Yuehua

    2002-01-01

    In the present paper, the therapeutic effects of auricular plaster (otopoint-pellet pressing therapy)and Western medicine (Dramamine) were compared in the treatment of 200 cases of motion sickness who were randomly divided into auricular plaster group (n = 135) and Western medicine (control) group (n = 65). Results indicated that the markedly effective rates and total effective rates of auricular plaster group and control group were 51. 1% and 23. 1 %, 94.1% and 81.6% respectively, and the therapeutic effect of the former group was significantly superior to that of the control group (P<0.01).

  13. Perspectives of Treatment Providers and Clients with Serious Mental Illness Regarding Effective Therapeutic Relationships.

    Science.gov (United States)

    Easter, Alison; Pollock, Michele; Pope, Leah Gogel; Wisdom, Jennifer P; Smith, Thomas E

    2016-07-01

    This study explores the nature of clinical therapeutic relationships between mental health treatment providers and high-need clients with serious mental illness who had recently discontinued treatment. Semi-structured qualitative interviews of 56 clients with serious mental illness who had recently discontinued care and 25 mental health treatment providers were completed. Both clients with serious mental illness and treatment providers emphasized the importance of client-focused goal setting, time and availability of treatment providers, a caring approach, and trust and honesty in the relationship. However, clients with serious mental illness placed greater emphasis on goals involving tangible services, a notable area of discord between the two groups. Individuals with serious mental illness and treatment providers agreed regarding several key elements to a positive clinical relationship. Further attention to client goals related to tangible services may serve to improve relationships between treatment providers and high-need clients with serious mental illness.

  14. Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

    Science.gov (United States)

    Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

    2015-01-01

    Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

  15. N-type calcium channel blockers: novel therapeutics for the treatment of pain.

    Science.gov (United States)

    Schroeder, C I; Doering, C J; Zamponi, G W; Lewis, R J

    2006-09-01

    Highly selective Ca(v)2.2 voltage-gated calcium channel (VGCC) inhibitors have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Cone snail venoms provided the first drug in class with FDA approval granted in 2005 to Prialt (omega-conotoxin MVIIA, Elan) for the treatment of neuropathic pain. Since this pioneering work, major efforts underway to develop alternative small molecule inhibitors of Ca(v)2.2 calcium channel have met with varied success. This review focuses on the properties of the Ca(v)2.2 calcium channel in different pain states, the action of omega-conotoxins GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved Ca(v)2.2 calcium channel therapeutics, and finally the development of small molecules for the treatment of chronic pain.

  16. Codependency and family cohesion and adaptability: changes during treatment in a therapeutic community.

    Science.gov (United States)

    Teichman, M; Basha, U

    1996-04-01

    Codependency is a significant factor in the understanding of addiction to psychoactive substances. The present study examined changes in the level of codependency and perceived family relationships of drug-using residents in the three therapeutic communities in Israel in the course of their treatment. The findings indicate significant changes in both the level of codependency and the residents' perceptions of their family relationships between the beginning and the reentry stages of their treatment. On the other hand, no significant associations were found between their level of codependency and their perceptions of their family relationships. The findings are discussed in relation to the nature of addiction, the family processes, the treatment in the therapeutic community, and the addicted person's perseverance in that community.

  17. Standardised classification of pre-release development in male-brooding pipefish, seahorses, and seadragons (Family Syngnathidae

    Directory of Open Access Journals (Sweden)

    Sommer Stefan

    2012-12-01

    Full Text Available Abstract Background Members of the family Syngnathidae share a unique reproductive mode termed male pregnancy. Males carry eggs in specialised brooding structures for several weeks and release free-swimming offspring. Here we describe a systematic investigation of pre-release development in syngnathid fishes, reviewing available data for 17 species distributed across the family. This work is complemented by in-depth examinations of the straight-nosed pipefish Nerophis ophidion, the black-striped pipefish Syngnathus abaster, and the potbellied seahorse Hippocampus abdominalis. Results We propose a standardised classification of early syngnathid development that extends from the activation of the egg to the release of newborn. The classification consists of four developmental periods – early embryogenesis, eye development, snout formation, and juvenile – which are further divided into 11 stages. Stages are characterised by morphological traits that are easily visible in live and preserved specimens using incident-light microscopy. Conclusions Our classification is derived from examinations of species representing the full range of brooding-structure complexity found in the Syngnathidae, including tail-brooding as well as trunk-brooding species, which represent independent evolutionary lineages. We chose conspicuous common traits as diagnostic features of stages to allow for rapid and consistent staging of embryos and larvae across the entire family. In view of the growing interest in the biology of the Syngnathidae, we believe that the classification proposed here will prove useful for a wide range of studies on the unique reproductive biology of these male-brooding fish.

  18. [Integration without equalization: on necessary modifications of therapeutic strategies in the treatment of migrants].

    Science.gov (United States)

    Behrens, Katharina; Calliess, Iris Tatjana

    2008-12-01

    Given an increased knowledge for the special requirements of patients with a history of migration in mental health care, different approaches varying between an adaptation of existing systems and the implementation of specialized institutions are being discussed. The present study investigates the treatment courses of 55 first generation immigrants and a control sample of 55 native patients treated in a psychiatric day clinic of a university clinic. Besides the application of questionnaires concerning treatment outcome, a detailed content analysis of treatment records was performed investigating the preference for different therapeutic approaches, migration- and culture-related aspects as well as language problems. Treatment outcome and the reactions to different therapeutic strategies (i. e., verbal-oriented vs. body-centered approaches) suggest a good fit of a common treatment concept also for patients from different countries of origin and ethnic backgrounds. Qualitative analyses, however, imply that migration biography and cultural diversity should be included in diagnostic and therapeutic considerations to a much bigger extent. Language problems, in contrast, appeared to be less salient in the present study.

  19. Human pluripotent stem cells:Towards therapeutic development for the treatment of lifestyle diseases

    Institute of Scientific and Technical Information of China (English)

    Miwako; Nishio; Masako; Nakahara; Akira; Yuo; Kumiko; Saeki

    2016-01-01

    There are two types of human pluripotent stem cells: Embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs),both of which launched themselves on clinical trials after having taken measures to overcome problems: Blocking rejections by immunosuppressants regarding ESCs and minimizing the risk of tumorigenicity by depleting exogenous gene components regarding iP SCs.It is generally assumed that clinical applications of human pluripotent stem cells should be limited to those cases where there are no alternative measures for treatments because of the risk in transplanting those cells to living bodies.Regarding lifestyle diseases,we have already several therapeutic options,and thus,development of human pluripotent stem cell-based therapeutics tends to be avoided.Nevertheless,human pluripotent stem cells can contribute to the development of new therapeutics in this field.As we will show,there is a case where only a short-term presence of human pluripotent stem-derived cells can exert long-term therapeutic effects even after they are rejected.In those cases,immunologically rejections of ESC-or allogenic iP SC-derived cells may produce beneficial outcomes by nullifying the risk of tumorigenesis without deterioration of therapeutic effects.Another utility of human pluripotent stem cells is the provision of an innovative tool for drug discovery that are otherwise unavailable.For example,clinical specimens of human classical brown adipocytes(BAs),which has been attracting a great deal of attention as a new target of drug discovery for the treatment of metabolic disorders,are unobtainable from living individuals due to scarcity,fragility and ethical problems.However,BA can easily be produced from human pluripotent stem cells.In this review,we will contemplate potential contribution of human pluripotent stem cells to therapeutic development for lifestyle diseases.

  20. Therapeutic impact of CT-guided percutaneous catheter drainage in treatment of deep tissue abscesses

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Nobuhiro; Ohkuni, Yoshihiro; Kaneko, Norihiro; Aoshima, Masahiro; Yamazaki, Ikuo; Kawamura, Yasutaka, E-mail: nobuhiro0204@hotmail.com [Kameda Medical Center, Chiba (Japan)

    2013-03-15

    Combination therapy of CT-guided percutaneous drainage and antibiotics is the first-line treatment for abscesses. Its effectiveness has been demonstrated. However, the therapeutic impact of this procedure for infection treatment has never been reported. We retrospectively analyzed all 47 patients who received CT-guided percutaneous drainage for infection treatment. Patients' characteristics, pathogens isolated, antibiotics administered, technical and clinical outcomes, complications related to this procedure and therapeutic impacts were investigated. Patients were 26 males and 21 females. The mean age was 63.5 years ({+-}18.7). The diseases targeted were 19 retroperitoneal abscesses, 18 intraabdominal abscesses, three pelvic abscesses, and seven others. As for technical outcomes, all of the 54 procedures (100%) were successful. As for clinical outcomes, 44 (93.6%) were cured and three patients (6.4%) died. No complications related to this procedure were found in this study. A total of 42 patients (88%) had a change in the management of their infection as a result of CT-guided percutaneous drainage, such as selection and discontinuation of antibiotics. In conclusion, CT-guided percutaneous drainage is a safe and favorable procedure in the treatment of deep tissue abscesses. Therapeutic impact of these procedures helped physicians make a rational decision for antibiotics selection. (author)

  1. Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

    Science.gov (United States)

    Li, Hai-feng; Zou, Yan; Ding, Gangqiang

    2013-01-01

    Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

  2. Therapeutic impact of CT-guided percutaneous catheter drainage in treatment of deep tissue abscesses.

    Science.gov (United States)

    Asai, Nobuhiro; Ohkuni, Yoshihiro; Yamazaki, Ikuo; Kaneko, Norihiro; Aoshima, Masahiro; Kawamura, Yasutaka

    2013-01-01

    Combination therapy of CT-guided percutaneous drainage and antibiotics is the first-line treatment for abscesses. Its effectiveness has been demonstrated. However, the therapeutic impact of this procedure for infection treatment has never been reported. We retrospectively analyzed all 47 patients who received CT-guided percutaneous drainage for infection treatment. Patients' characteristics, pathogens isolated, antibiotics administered, technical and clinical outcomes, complications related to this procedure and therapeutic impacts were investigated. Patients were 26 males and 21 females. The mean age was 63.5 years (±18.7). The diseases targeted were 19 retroperitoneal abscesses, 18 intra-abdominal abscesses, three pelvic abscesses, and seven others. As for technical outcomes, all of the 54 procedures (100%) were successful. As for clinical outcomes, 44 (93.6%) were cured and three patients (6.4%) died. No complications related to this procedure were found in this study. A total of 42 patients (88%) had a change in the management of their infection as a result of CT-guided percutaneous drainage, such as selection and discontinuation of antibiotics. In conclusion, CT-guided percutaneous drainage is a safe and favorable procedure in the treatment of deep tissue abscesses. Therapeutic impact of these procedures helped physicians make a rational decision for antibiotics selection.

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

    Directory of Open Access Journals (Sweden)

    Gupta R

    2014-01-01

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

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

    Science.gov (United States)

    Gupta, Ram; Chaudhary, Anita R; Shah, Binita N; Jadhav, Avinash V; Zambad, Shitalkumar P; Gupta, Ramesh Chandra; Deshpande, Shailesh; Chauthaiwale, Vijay; Dutt, Chaitanya

    2014-01-01

    Background and aim Mucosal healing in inflammatory bowel disease (IBD) can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF) has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn’s disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor ameliorates IBD in disease models. These findings highlight the potential of TRC160334 for its clinical application in the treatment of IBD. PMID:24493931

  5. Plant alkaloids as an emerging therapeutic alternative for the treatment of depression

    Directory of Open Access Journals (Sweden)

    Sadia ePervez

    2016-02-01

    Full Text Available Depression is a heterogeneous mood disorder that has been classified and treated in a variety of ways. Although a number of synthetic drugs are being used as standard treatment for clinically depressed patients, but they have adverse effects that can compromise the therapeutic treatments and patient's compliance. Unlike, synthetic medications, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy associated with least side effects, which in turn has initiated the scientific research regarding the antidepressant activity. This review is mostly based on the literature of the last decade, aimed at exploring the preclinical profile of plant-based alkaloids (the abundant secondary metabolite as an emerging therapy for depression.

  6. Reasons for the treatment of users of crack in a therapeutic community

    Directory of Open Access Journals (Sweden)

    Maycon Rogério Seleghim

    2015-07-01

    Full Text Available Objective: Knowing the motivation of crack users for treatment in hospital environments. Method: Descriptive and qualitative search, using the design of some cases. Twenty male crack users, aged over 18 years old, hospitalized in a Therapeutic Community in Southern Brazil, were interviewed. A semi-structured interview was used and the data were analyzed by their thematic content. Results: Were found three categories that reflect the treatment motivations: perception of the crack harmful consequences; the compulsive use of drugs as the treatment initiation; and, the family participation looking for a treatment. Conclusion: Significant events (turning points favored the interruption of the crack use and the family assumed a very important place to the users behavior in relation to the use of the drug, exclusively. Descriptors: Street drugs, Crack Cocaine, Substance Abuse Treatment Centers, Family.

  7. Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication

    OpenAIRE

    2016-01-01

    Abstract 1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenous antioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or w...

  8. Therapeutic switching in leishmania chemotherapy: a distinct approach towards unsatisfied treatment needs

    OpenAIRE

    Shakya, Nishi; Bajpai, Preeti; Gupta, Suman

    2011-01-01

    Current drugs for the treatment of visceral leishmaniasis are inadequate. No novel compound is in the pipeline. Since economic returns on developing a new drug for neglected disease, leishmaniasis is so low that therapeutic switching represents the only realistic strategy. It refers to “alternative drug use” discoveries which differ from the original intent of the drug. Amphotericin B, paromomycin, miltefosine and many other drugs are very successful examples of “new drugs from old”. This art...

  9. Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia

    OpenAIRE

    2016-01-01

    Therapeutic hypothermia (HT) is standard care for moderate and severe neonatal hypoxic-ischaemic encephalopathy (HIE), the leading cause of permanent brain injury in term newborns. However, the optimal temperature for HT is still unknown, and few preclinical studies have compared multiple HT treatment temperatures. Additionally, HT may not benefit infants with severe encephalopathy. In a neonatal rat model of unilateral hypoxia-ischaemia (HI), the effect of five different HT temperatures was ...

  10. Molecular Markers and Targeted Therapeutics in Metastatic Tumors of the Spine: Changing the Treatment Paradigms.

    Science.gov (United States)

    Goodwin, C Rory; Abu-Bonsrah, Nancy; Rhines, Laurence D; Verlaan, Jorrit-Jan; Bilsky, Mark H; Laufer, Ilya; Boriani, Stefano; Sciubba, Daniel M; Bettegowda, Chetan

    2016-10-15

    A review of the literature. The aim of this study was to discuss the evolution of molecular signatures and the history and development of targeted therapeutics in metastatic tumor types affecting the spinal column. Molecular characterization of metastatic spine tumors is expected to usher in a revolution in diagnostic and treatment paradigms. Molecular characterization will provide critical information that can be used for initial diagnosis, prognosticating the ideal treatment strategy, assessment of treatment efficacy, surveillance and monitoring recurrence, and predicting complications, clinical outcome, and overall survival in patients diagnosed with metastatic cancers to the spinal column. A review of the literature was performed focusing on illustrative examples of the role that molecular-based therapeutics have played in clinical outcomes for patients diagnosed with metastatic tumor types affecting the spinal column. The impact of molecular therapeutics including receptor tyrosine kinases and immune checkpoint inhibitors and the ability of molecular signatures to provide prognostic information are discussed in metastatic breast cancer, lung cancer, prostate cancer, melanoma, and renal cell cancer affecting the spinal column. For the providers who will ultimately counsel patients diagnosed with metastases to the spinal column, molecular advancements will radically alter the management/surgical paradigms utilized. Ultimately, the translation of these molecular advancements into routine clinical care will greatly improve the quality and quantity of life for patients diagnosed with spinal malignancies and provide better overall outcomes and counseling for treating physicians. N/A.

  11. OBSERVATION ON THE THERAPEUTIC EFFECT OF ELECTROACUPUNCTURE TREATMENT FOR SIMPLE CHRONIC RHINITIS

    Institute of Scientific and Technical Information of China (English)

    WEN Biling; ZHOU Shuang; YANG Yihong

    2002-01-01

    @@ Simple chronic rhinitis is a reversible chronic inflammatory disorder of nasal mucosa caused by various factors, it is a frequently encountered disorder with clinical manifestations of increased nasal secretion, intermittent alternative nasal obstruction, frequent ( respiratory ) anosmia and rhinophonia while speaking. In severe cases, it may manifest as hypocathexis, hypomnesis, fatigue, headache, head distress, insomnia, etc.that considerably hinder the patient's work or study. In the last 10 years, the authors have chiefly applied electroacupuncture (EA) to treatment of 38 cases of chronic rhinitis and the therapeutic effects are satisfactory. The following is the report of the treatment.

  12. Rannasangpei Is a Therapeutic Agent in the Treatment of Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Peng Wu

    2016-01-01

    Full Text Available Rannasangpei (RSNP is used as a therapeutic agent in the treatment of cardiovascular diseases, neurological disorders, and neurodegeneration in China; however, its potential use in the treatment of vascular dementia (VD was unclear. In this study, our aim was to examine the neuroprotective effect of RSNP in a VD rat model, which was induced by permanent bilateral common carotid artery occlusion (2VO. Four-week administration with two doses of RSNP was investigated in our study. Severe cognitive deficit in the VD model, which was confirmed in Morris water maze (MWM test, was significantly restored by the administration of RSNP. ELISA revealed that the treatments with both doses of RSNP could reinstate the cholinergic activity in the VD animals by elevating the production of choline acetyltransferase (ChAT and reducing the acetylcholinesterase (AChE; the treatment of RSNP could also reboot the level of superoxide dismutase (SOD and decrease malondialdehyde (MDA. Moreover, Western blot and quantitative PCR (Q-PCR results indicated that the RSNP could suppress the apoptosis in the hippocampus of the VD animals by increasing the expression ratio of B-cell lymphoma-2 (Bcl-2 to Bcl-2-associated X protein (Bax. These results suggested that RSNP might be a therapeutic agent in the treatment of vascular dementia in the future.

  13. Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis.

    Science.gov (United States)

    Zuur, Marlanka A; Bolhuis, Mathieu S; Anthony, Richard; den Hertog, Alice; van der Laan, Tridia; Wilffert, Bob; de Lange, Wiel; van Soolingen, Dick; Alffenaar, Jan-Willem C

    2016-05-01

    Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment.

  14. Therapeutic Effect Observation on Treatment of Acne with Acupuncture plus Moving Cupping and Blood-letting

    Institute of Scientific and Technical Information of China (English)

    WANG Qi-fang; WANG Guo-yan; HAN Chou-ping

    2008-01-01

    目的:观察针刺配合刺络走罐治疗痤疮的疗效.方法:将60例痤疮患者随机分为两组,治疗组采用针刺配合刺络走罐;对照组采用针刺治疗,两组均治疗30天后观察疗效.结果:治疗组总有效率明显高于对照组(P<0.05).结论:针刺配合刺络走罐治疗痤疮能有效提高该病的有效率.%Objective: To observe the therapeutic effect on treatment of acne with acupuncture plus moving cupping and blood-letting. Method: Sixty acne cases were randomized into the treatment group for combined acupuncture and moving cupping and blood-letting and control group for acupuncture alone. The therapeutic effects of the cases in the two groups were observed after a 30-day treatment. Result: The total effective rate was significantly higher in the treatment group than in the control group (P<0.05). Conclusion: The combined acupuncture and moving cupping and blood-letting can effectively increase the effective rate in the treatment of acne.

  15. Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

    Science.gov (United States)

    Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. ANALYSIS ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE TREATMENT OF 2656CASES OF PRIMARY TRIGEMINAL NEURALGIA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In the present paper,the clinical therapeutic effect of acupuncture therapy for treat-ment of primary prosopalgia was observed and its influencing factors were analyzed in 2656 patients.Yuyao(EX-HN4),Touwei(ST8),Sibai(ST2),Quanliao(SI18),Xiaguan(ST7)and Ji-achengjiang were punctured selectively according to the involvement of different branches of the trigeminal nerve.After treatment,of the 2656cases,the trigeminal neuralgia disappeared in 1469(55.31),727(27.37%)had marked improvement,430(16.19%)had improvement and 30(1.13%)had no any significant effect.The three years'follow-up visit in 245cases showed a relapse in 187cases(76.3%).We think that the therapeutic effect is closely related to the needling manipula-tions.Only when an electric shock-like needing sensation appeared(i.e.“qi reaching th affected area”)after inserting the acupuncture needle into the chief acupoints,a better therapeutic effect would be achived.

  17. Novel Therapeutic Approaches to the Treatment of Chronic Abdominal Visceral Pain

    Directory of Open Access Journals (Sweden)

    Franca Patrizi

    2006-01-01

    Full Text Available Chronic abdominal visceral pain (CAVP has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS, might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

  18. A reinforcement-based therapeutic workplace for the treatment of drug abuse: three-year abstinence outcomes.

    Science.gov (United States)

    Silverman, Kenneth; Svikis, Dace; Wong, Conrad J; Hampton, Jacqueline; Stitzer, Maxine L; Bigelow, George E

    2002-08-01

    Long-term Therapeutic Workplace effects were evaluated in heroin- and cocaine-dependent, unemployed, treatment-resistant young mothers. Participants were paid to work or to train in the Therapeutic Workplace but had to provide drug-free urine samples to gain daily access. Participants (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants could work for 3 years. Relative to controls, Therapeutic Workplace participants increased cocaine (28% vs. 54% negative; p = .04) and opiate (37% vs. 60% negative; p = .05) abstinence on the basis of monthly urine samples collected until 3 years after intake. The Therapeutic Workplace can be an effective long-term treatment of cocaine and heroin addiction in poor and chronically unemployed young mothers.

  19. [Therapeutic holidays in osteoporosis: Long-term strategy of treatment with bisphosphonates].

    Science.gov (United States)

    Moro Álvarez, María Jesús; Neyro, José Luis; Castañeda, Santos

    2016-01-01

    Oral bisphosphonates (BF) are drugs widely used in the treatment of osteoporosis and placed as first-line treatment for osteoporosis in most clinical guidelines. BF are effective drugs that reduce the incidence of fractures and even reduce mortality. Because of their great affinity for bone, BF have shown that even when they are discontinued still offer a latent protective effect on bone mineral density, maintaining their anti-fracture effect. However, prolonged use for years has been linked to the gradual emergence of complications such as osteonecrosis of the jaw or atypical femur fractures, which have raised questions as when to hold and when to make a final or temporary break, recognized as periods of rest or "therapeutic holidays" of these drugs. Thus, in patients treated with BF for a period of 3-5 years with a low risk of fracture, the drug should be discontinued and restarted when there is an indication for treatment. In contrast, in patients with moderate risk, therapeutic holidays are advised, while reassessing after 2-3 years for restarting purposes. Finally, in patients with high risk of fracture, treatment with BF should not be withdrawn. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Treatment Model in Children with Speech Disorders and Its Therapeutic Efficiency

    Directory of Open Access Journals (Sweden)

    Barberena, Luciana

    2014-05-01

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

  1. Caries preventive efficiency of therapeutic complex accomponying orthodontic treatment of children with initial dental caries

    Directory of Open Access Journals (Sweden)

    Denga A.E.

    2013-12-01

    Full Text Available The use of orthodontic non-removable appliance in orthodontic treatment inter¬feres with the process of teeth mineralization, worsens level of oral cavity hygiene, stimulates development of caries process. The situation is complicated when a patient has an initial tooth decay. The aim of this study was to determine genetic characteristics of children with initial caries and clinical evaluation of effectiveness of the developed caries preventive therapeutic complex accompanying treatment of jaw facial anomalies (JFA. 47 children aged 12-14 with initial tooth decay participated in the examination. Complex diagnostics, including molecular genetic studies was carried out. Therapeutic complex for children, of the main group included remineralizing, adaptogenic, biogenic agents, which increase non-specific resistance, as well as infiltration ICON therapy before fixing braces. Caries preventive complex accompanying JFA treatment in children with primary tooth decay developed with regard to revealed genetic disorders of amelogenesis, 2-nd of phase detoxification, collagen formation, functional responses in the oral cavity, state of hard tissues of teeth and periodontal tissues enabled to preserve existing carious process, normalize periodontal and hygienic indices at all stages of treatment.

  2. Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents

    Directory of Open Access Journals (Sweden)

    Steve D Wilton

    2011-03-01

    Full Text Available Steve D Wilton, Sue FletcherCentre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, Perth, WA, AustraliaAbstract: The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD was expected to lead to timely development of effective therapies. Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals. Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments. Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms.Keywords: Duchenne muscular dystrophy, molecular therapeutics, small molecules

  3. The therapeutic use of localized cooling in the treatment of VX poisoning.

    Science.gov (United States)

    Sawyer, T W; Mikler, J; Worek, F; Reiter, G; Thiermann, H; Tenn, C; Weatherby, K; Bohnert, S

    2011-07-04

    The organophosphate (OP) nerve agent VX is a weaponized chemical warfare agent that has also been used by terrorists against civilians. This contact poison produces characteristic signs of OP poisoning, including miosis, salivation, mastication, dysrhythmias and respiratory distress prior to death. Although successful treatment of OP poisoning can be obtained through decontamination and/or oxime reactivation of agent-inhibited cholinesterase, medical countermeasures that increase the therapeutic window for these measures would be of benefit. An anaesthetized swine model was utilized to examine the effects of lethal VX exposure to the skin, followed by cooling the exposure site prior to decontamination or treatment. The cooling was simply accomplished by using crushed ice in grip-seal plastic bags applied to the exposure sites. Cooling of skin exposed to lethal doses of VX significantly increased the window of opportunity for successful decontamination using the Reactive Skin Decontaminant Lotion(®) (RSDL(®)) or treatment with the oxime antidotes HI-6 and 2PAM. Analyses of blood VX levels showed that cooling acted to slow or prevent the entry of VX into the bloodstream from the skin. If the exposure site is known, the simple and non-invasive application of cooling provides a safe means with which to dramatically increase the therapeutic window in which decontamination and/or antidote treatment against VX are life-saving.

  4. Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence--qualitative results.

    Science.gov (United States)

    Loizaga-Velder, Anja; Verres, Rolf

    2014-01-01

    This qualitative empirical study explores the ritual use of ayahuasca in the treatment of addictions. Ayahuasca is an Amazonian psychedelic plant compound created from an admixture of the vine Banisteriopsis caapi and the bush Psychotria viridis. The study included interviews with 13 therapists who apply ayahuasca professionally in the treatment of addictions (four indigenous healers and nine Western mental health professionals with university degrees), two expert researchers, and 14 individuals who had undergone ayahuasca-assisted therapy for addictions in diverse contexts in South America. The study provides empirically based hypotheses on therapeutic mechanisms of ayahuasca in substance dependence treatment. Findings indicate that ayahuasca can serve as a valuable therapeutic tool that, in carefully structured settings, can catalyze neurobiological and psychological processes that support recovery from substance dependencies and the prevention of relapse. Treatment outcomes, however, can be influenced by a number of variables that are explained in this study. In addition, issues related to ritual transfer and strategies for minimizing undesired side-effects are discussed.

  5. A fuzzy approach to evaluation and management of therapeutic procedure in diabetes mellitus treatment

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    Tadić Danijela

    2010-01-01

    Full Text Available In this paper a new fuzzy model (FMOTPD2 is developed and by this model the measures of beliefs are determined so that one of the groups of possible therapeutic procedures is optimal for each patient of type 2 diabetes on hospital treatment. The choice of therapeutic procedure on individual level, which is one of the demands of modern medicine, means that each therapeutic procedure is to be evaluated by multiple and different criteria. In this paper, evaluation criteria are classified into two groups: (1 common criteria by which medicines used by the type 2 diabetes patients are being evaluated and (2 specific criteria, by which the patients' 1h state of health with type 2 diabetes mellitus is being estimated. Generally, the relative importance and values of these criteria are different. It is assumed that (a the relative importance of evaluation criteria is defined by a team of medical experts and described by linguistic expressions and (b the values of evaluation criteria are determined by evidence data, anamnesis and a diagnostic process. They can be crisp or uncertain. The most often used linguistic expressions describing the relative importance of evaluation criteria are modeled by triangular fuzzy numbers. The rest of uncertainties, which exist in developed model are described by discrete fuzzy numbers. A new algorithm for determining a unified fuzzy portrait of treated therapeutic procedures for each patient is given. It enables calculation of the measures of beliefs that some therapeutic procedures are more optimal than the others. The developed model is illustrated by examples with real word data collected in a hospital.

  6. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions

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    Gina M Graziani

    2015-11-01

    Full Text Available Introduction: The development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART, would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates. Discussion: This review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy. Conclusions: Given the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of

  7. Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: a systematic review.

    Science.gov (United States)

    Khunti, Kamlesh; Gomes, Marilia B; Pocock, Stuart; Shestakova, Marina V; Pintat, Stéphane; Fenici, Peter; Hammar, Niklas; Medina, Jesús

    2017-08-22

    Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner according to evidence-based clinical guidelines, is a key reason for uncontrolled hyperglycaemia in patients with type 2 diabetes. The aims of this systematic review were to identify how therapeutic inertia in the management of hyperglycaemia was measured and to assess its extent over the past decade. Systematic searches for articles published from 1 January 2004 to 1 August 2016 were conducted in MEDLINE and Embase. Two researchers independently screened all of the titles and abstracts, and the full texts of publications deemed relevant. Data were extracted by a single researcher using a standardized data extraction form. The final selection for the review included 53 articles. Measurements used to assess therapeutic inertia varied across studies, making comparisons difficult. Data from low- to middle-income countries were scarce. In most studies, the median time to treatment intensification after a glycated haemoglobin (HbA1c ) measurement above target was more than 1 year (range 0.3 to >7.2 years). Therapeutic inertia increased as the number of antidiabetic drugs rose and decreased with increasing HbA1c levels. Data were mainly available from Western countries. Diversity of inertia measures precluded meta-analysis. Therapeutic inertia in the management of hyperglycaemia in patients with type 2 diabetes is a major concern. This is well documented in Western countries, but corresponding data are urgently needed in low- and middle-income countries, in view of their high prevalence of type 2 diabetes. This article is protected by copyright. All rights reserved.

  8. [Triazole antifungal agents: practice guidelines of therapeutic drug monitoring and perspectives in treatment optimization].

    Science.gov (United States)

    Scodavolpe, Simon; Quaranta, Sylvie; Lacarelle, Bruno; Solas, Caroline

    2014-01-01

    Antifungal triazole agents (fluconazole, voriconazole, itraconazole and posaconazole) are widely used for the management of invasive fungal infections (IFI). These drugs are indicated both for the prophylaxis and treatment of IFI, particularly in candidiasis and aspergillosis, major cause of mortality in immunocompromised patients. Due to a large interindividual pharmacokinetic variability leading to sub-therapeutic or toxic concentrations and to concentration-efficacy and/or -toxicity relationships, therapeutic drug monitoring (TDM) of antifungal triazole is fully justified. This review provides an overview of literature based data that confirm the usefulness of such TDM and its level of evidence as well as the practical guidelines for its implementation. In addition, we discuss the interest of new tools to improve the clinical management of IFI, such as genotyping tests optimizing initial voriconazole dosing regimen or the development of a new solid oral tablet of posaconazole improving its bioavailability and limiting absorption disorders.

  9. Fluconazole and its place in the treatment of seborrheic dermatitis--new therapeutic possibilities.

    Science.gov (United States)

    Zisova, Lilija G

    2006-01-01

    Seborrheic dermatitis is a subacute or chronic disease of the skin, affecting the seborrhea afflicted areas and presenting with erythema and desquamation. The inflammatory reaction towards the fungi Malassezia spp. is considered to have a basic etiologic connection with this disease. Taking into consideration the pathogenesis, treatment of the dermatitis should be directed towards eradication of Malassezia spp., reduction of the skin lipids, and suppression of the inflammatory response. A wide variety of agents presented in different forms--ointments, shampoos and drugs--can offer quick, safe and effective treatment alternatives. The purpose of the present study was to monitor the therapeutic effects of the anti-fungal drug fluconazole in patients with seborrheic dermatitis. We compared two study groups of patients: Group I--27 patients with seborrheic dermatitis stage I, II and III, treated with fluconazole, 50 mg/day for two weeks. As topical therapy we applied clobetasol propionate 0.05% ointment. After the completion of the therapeutic course, 85% of the patients in this group were clinically cured and their symptoms faded away. Fifteen percent of the subjects in this group--mainly stage III seborrheic dermatitis patients, showed partial but significant clinical improvement. The specific fungal test for Malassezia spp. on Dixon agar was negative in 93% of the cases in this group. Group II--eleven patients with similar clinical indexes were treated with fluconazole 50 mg/day only, for the same time period. The therapeutic results in this group were also satisfactory--31.5% of the patients were cured and 68.5% showed clinical improvement. In 74% of the patients the specific test for Malassezia spp. was negative after treatment. Fluconazole treatment in patients with seborrheic dermatitis proves to be successful, effective and safe.

  10. Influence of comorbidities on therapeutic progression of diabetes treatment in Australian veterans: a cohort study.

    Directory of Open Access Journals (Sweden)

    Agnes I Vitry

    Full Text Available BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20,134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P<0.001. Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS/SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.

  11. Novel therapeutic approaches for the treatment of castration-resistant prostate cancer.

    Science.gov (United States)

    Heidegger, Isabel; Massoner, Petra; Eder, Iris E; Pircher, Andreas; Pichler, Renate; Aigner, Friedrich; Bektic, Jasmin; Horninger, Wolfgang; Klocker, Helmut

    2013-11-01

    Prostate cancer is a leading cause of cancer death in men in developed countries. Once the tumor has achieved a castration-refractory metastatic stage, treatment options are limited with the average survival of patients ranging from two to three years only. Recently, new drugs for treatment of castration-resistant prostate cancer (CRPC) have been approved, and others are in an advanced stage of clinical testing. In this review we provide an overview of the new therapeutic agents that arrived in the clinical praxis or are tested in clinical studies and their mode of action including hormone synthesis inhibitors, new androgen receptor blockers, bone targeting and antiangiogenic agents, endothelin receptor antagonists, growth factor inhibitors, novel radiotherapeutics and taxanes, and immunotherapeutic approaches. Results and limitations from clinical studies as well as future needs for improvement of CRPC treatments are critically discussed.

  12. Research Progress of Therapeutic Endoscopy in the Treatment of Pancreaticobiliary Disease

    Institute of Scientific and Technical Information of China (English)

    CAI Lei; CHENG Yuan; CAI Li-quan; PAN Ming-xin; GAO Yi

    2014-01-01

    Pancreaticobiliary diseases, which include cholecystitis, choledocholithiasis, cholangitis, malignant biliary stricture, pancreatic pseudocyst and pancreatic cancer, have increasing morbidity and mortality year by year and severely threaten human lives, for which there are many therapeutic methods in clinic. The promotion of endoscopic otomy and the development of new devices have greatly improved the successful rate of endoscopic retrograde cholangiopancreatology (ERCP). Additionally, with the development of non-invasive diagnostic technique for pancreatic disease like magnetic resonance cholangiopancreatography, ERCP can also be widely used in the treatment of pancreatic diseases. Therefore, this study mainly reviewed the application of ERCP in the treatment of pancreaticobiliary diseases, hoping to improve the survival rate of patients and provide basis for the clinical treatment.

  13. Improving Therapeutic Ratio in Head and Neck Cancer with Adjuvant and Cisplatin-Based Treatments

    Directory of Open Access Journals (Sweden)

    Loredana G. Marcu

    2013-01-01

    Full Text Available Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients.

  14. Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

    Science.gov (United States)

    Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

    2017-03-01

    Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

  15. Relation between Treatment Course and Therapeutic Effects of Acupuncture for Female Obesity of Diffrerent Types

    Institute of Scientific and Technical Information of China (English)

    SUN Hong

    2008-01-01

    objective;To observe the relationship between treatment course and therapeutic effect of acupuncture on female obesity in different types.Methods;The 83 cases of obesity were divided into two groups;abdominal obesity group(AO,31 cases)and symmetrical obesity group(SO,52 cases).All of them were treated by acupuncture for 3 months,1 month as one course.Results;In Group AO,after one month of treatment,body mass index(BMI),waist circumference(WC)and skin fat thickness(SFT)in the upper limbs(A),trunk(B)and abdomen(at locations C and D)were very significantly reduced(P<0.01);After 2 months of treatment,BMI,WC and SFT at C were also very significantly reduced(P<0.01),SFT in A and at D was significantly reduced(p<0.05),but no significant SFT difference was found in B(P>0.05);And after 3 months of treatment,no difference was found in any indices.In Group SO,all the indices including BMI,WC and SFTim A,B,C and D were reduced in the successive 3 months of treatment (P<0.01).Conclusions;The therapeutic effect of acupuncture on abdominal obesity was gradually Iessened with the prolonging of treatment course,even without further advance after reaching the normal body weight range.But for symmetrical obesity,tbe effect was gradually advanced to reach the normal range.That tgeir body weight in a normal range will be kept stable without further reduction remains to be studied further

  16. [Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

    Science.gov (United States)

    Allouche, G

    2016-02-01

    Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses

  17. Therapeutic potential of Panax ginseng and ginsenosides in the treatment of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Shergis, J L; Di, Y M; Zhang, A L; Vlahos, R; Helliwell, R; Ye, J M; Xue, C C

    2014-10-01

    Chronic obstructive pulmonary disease (COPD) is a major global health burden and will become the third largest cause of death in the world by 2030. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, cause progressive airflow limitation. This inflammation, where macrophages, neutrophils and lymphocytes are prominent, leads to oxidative stress, emphysema, airways fibrosis and mucus hypersecretion. COPD responds poorly to current anti-inflammatory treatments including corticosteroids, which produce little or no benefit. Panax ginseng has a long history of use in Chinese medicine for respiratory conditions, including asthma and COPD. In this perspective we consider the therapeutic potential of Panax ginseng for the treatment of COPD. Panax ginseng and its compounds, ginsenosides, have reported effects through multiple mechanisms but primarily have anti-inflammatory and anti-oxidative effects. Ginsenosides are functional ligands of glucocorticoid receptors and appear to inhibit kinase phosphorylation including MAPK and ERK1/2, NF-κB transcription factor induction/translocation, and DNA binding. They also inhibit pro-inflammatory mediators, TNF-α, IL-6, IL-8, ROS, and proteases such as MMP-9. Panax ginseng protects against oxidative stress by increasing anti-oxidative enzymes and reducing the production of oxidants. Given that Panax ginseng and ginsenosides appear to inhibit processes related to COPD pathogenesis, they represent an attractive therapeutic target for the treatment of COPD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  19. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  20. Therapeutic application of dysprosium-165-FHMA in the treatment of rheumatoid knee effusions

    Energy Technology Data Exchange (ETDEWEB)

    English, R.J.; Zalutsky, M.; Venkatesan, P.; Sledge, C.B.

    1986-03-01

    Radiation synovectomy utilizing a variety of radionuclides has proven to be an effective technique in the treatment of rheumatoid arthritis. The recent introduction of the short-lived radionuclide, Dysprosium-165 (/sup 165/Dy), as a replacement for the longer-lived radiocolloids has reduced nontarget dosimetry caused by leakage of the agent from the articular cavity. A review of the methods and status of radiation synovectomy, and the application of /sup 165/Dy-ferric hydroxide macroaggregates (FHMA) as an alternative therapeutic agent is described.

  1. RNAi therapeutics and applications of microRNAs in cancer treatment.

    Science.gov (United States)

    Uchino, Keita; Ochiya, Takahiro; Takeshita, Fumitaka

    2013-06-01

    RNA interference-based therapies are proving to be powerful tools for combating various diseases, including cancer. Scientists are researching the development of safe and efficient systems for the delivery of small RNA molecules, which are extremely fragile in serum, to target organs and cells in the human body. A dozen pre-clinical and clinical trials have been under way over the past few years involving biodegradable nanoparticles, lipids, chemical modification and conjugation. On the other hand, microRNAs, which control the balance of cellular biological processes, have been studied as attractive therapeutic targets in cancer treatment. In this review, we provide an overview of RNA interference-based therapeutics in clinical trials and discuss the latest technology for the systemic delivery of nucleic acid drugs. Furthermore, we focus on dysregulated microRNAs in human cancer, which have progressed in pre-clinical trials as therapeutic targets, and describe a wide range of strategies to control the expression levels of endogenous microRNAs. Further development of RNA interference technologies and progression of clinical trials will contribute to the achievement of practical applications of nucleic acid drugs.

  2. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

    Science.gov (United States)

    Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

    2004-08-01

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  3. Effect of comprehensive intervention on the therapeutic effect and treatment compliance in elderly patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    Li-Ming Zhang

    2016-01-01

    Objective:To explore the effect of comprehensive intervention on the therapeutic effect and treatment compliance in elderly patients with hypertension. Methods:A total of 110 elderly patients with hypertension who were admitted in our hospital were included in the study and randomized into the intervention group (n=56) and the control group (n=54). The patients in the two groups were given pressure controlling drugs and symptomatic treatment. On this basis, the patients in the intervention group were given the comprehensive intervention. The blood pressure controlling and medication compliance change on admission, and 4 and 8 weeks after treatment in the two groups were compared. SF-36 living quality rating scale was used to evaluate the living quality after hospital discharge. Results:The comparison of SBP and DBP before intervention between the two groups was not statistically significant. SBP and DBP 4 and 8 weeks after treatment were significantly reduced when compared with on admission. SBP and DBP 4 and 8 weeks after treatment in the intervention group were significantly lower than those in the control group. The medication compliance after intervention in the intervention group was significantly higher than that in the control group. The improvement of living quality after intervention in the intervention group was significantly superior to that in the control group. Conclusions:The comprehensive intervention in the treatment of senile hypertension can enhance the medication compliance, effectively control and stabilize the blood pressure, and improve the living quality.

  4. Group treatment for child sexual abuse: treatment referral and therapeutic outcomes.

    Science.gov (United States)

    Liotta, Lindsay; Springer, Craig; Misurell, Justin R; Block-Lerner, Jennifer; Brandwein, David

    2015-01-01

    A quasi-experimental design was used to compare the effectiveness of group (game-based cognitive behavioral) therapy to group-plus-individual therapy for child sexual abuse. The sample consisted predominantly of children from economically disadvantaged, African-American or Latino backgrounds. Pretreatment scores were examined in order to determine which factors influence treatment referral decisions. Results suggest that children who were referred for individual therapy in addition to group therapy report higher pretreatment levels of sexualized behavior. Posttreatment differences were also compared across therapy conditions. Results suggest that individual therapy is needed to address the sexual concerns of survivors but that it may not be needed to augment the effects of group therapy for other symptoms. Implications for treatment are discussed.

  5. Therapeutic effects of blood purification in treatment of fulminant hepatic failure

    Directory of Open Access Journals (Sweden)

    Yunchuan Pu

    2013-08-01

    Full Text Available OBJECTIVES: To evaluate the clinical effects of blood purification for treating fulminant hepatic failure (FHF. METHODS: Thirty-three severe FHF patients with hepatic encephalopathy (HE above grade III were subjected to a combined blood purification treatment in addition to the comprehensive liver protection therapy. Patients underwent continuous hemofiltration on a daily basis during the daytime followed by sequential treatment with plasma exchange or hemodialysis every 2-3 days. The therapeutic effects of this treatment were evaluated. RESULTS: After treatment with blood purification, restoration of consciousness (those who abandoned the treatment without restoration of consciousness were excluded was achieved in 6 of 8 cases (75% in acute liver failure (ALF group, 3 of 3 cases (100% in subacute liver failure (SALF group, and 9 of 14 cases (64.29% in acute/subacute on chronic liver failure (A/SCLF group. Of all cases, 11 patients restored consciousness after 7 days in a coma. The rate of long-term survival (those who abandoned the treatment were excluded was 3/7 (42.86% for ALF group, 2/2 (100% for SALF group, and 1/11 (9.09% for A/SCLF group. The levels of hemoglobin and platelet in peripheral blood were significantly reduced after blood purification. CONCLUSIONS: Treatment of FHF patients with daily continuous hemofiltration during the daytime is effective in treating HE and in improving health status in the early stages of the disease. Long-term prognosis also benefits from this treatment. The rate of consciousness recovery and long-term survival is highest in SALF group followed by ALF group. This treatment is less effective in A/SCLF patients. It should be noted that blood purification procedure may cause damage to blood cells.

  6. Observations on Therapeutic Effect of Back-Shu Acupoint in Treatment of Asthma

    Institute of Scientific and Technical Information of China (English)

    徐斯伟

    2008-01-01

    目的:观察背俞穴治疗哮喘的疗效.方法:将61例患者分为背俞穴组、针灸组、针刺组,三组均每星期治疗2次,10次为1疗程,治疗3疗程后观察疗效.结果与结论:背俞穴组和针灸组控显率均高于常规针刺组(P<0.05),针灸组控显率略高于背俞穴组,但没有统计学意义.结果表明背俞穴治疗哮喘有较好的疗效.%Objective: To investigate the therapeutic effect of Back-Shu acupoint in treating asthma. Methods: Sixty-one patients were randomly divided into a Back-Shu acupoint group, a acupuncture-moxibustion group and a acupuncture group. All the three groups were treated twice a week, 10 times made up a treatment course. The therapeutic effect was evaluated after three courses of treatment. Results and conclusion: The control and marked effective rate were significantly higher in the Back-Shu acupoint group and acupuncture-moxibustion groups than in the acupuncture group (P<0.05). They were slightly higher in the acupuncture-moxibustion group than in the Back-Shu acupoint group, but there was no statistically significant difference. The results indicated that the Back-Shu acupoints have a good therapeutic effect in treating asthma.

  7. ECONOMIC ASPECTS OF THERAPEUTIC EYELID HYGIENE IN MEIBOMIAN GLAND DYSFUNCTION TREATMENT

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2015-01-01

    Full Text Available The value of dry eye for general public health increases due to its high occurence in elderly persons and aging population. Non-specific questionnaires are adopted for dry eye. Additionally, 36‑item Medical Outcomes Study-Short Form (MOS-SF-36 and benefit evaluation method were developed. Methods. Information analysis and mathematical methods and public health technology evaluation methods (i.e., modelling, analysis of disease burden, and budget impact analysis were applied to economic aspect study. Decision tree model based on these finding was developed and applied to cost estimating of blepharoconjunctival and exogenous dry eye treatment in computer vision syndrome. Two scenarios of patient management were considered, i.e., typical management and management using therapeutic eyelid hygiene. Similar model was developed for early postoperative period after LASIK. Short-run analysis (1 year was performed, direct medical costs were considered. This analysis implies the calculation of overall cost (economic burden of the disease. Official data on adult population size in 2014 and the occurrence of the disease were used to assess prevalence. Budget impact analysis evaluates the difference in total economic effects due to comparison technology use in money terms. Sensitivity analysis assesses the stability of simulation results. Medical treatment cost was considered the most valuable parameter. Results and conclusions. Direct medical costs of typical management and management using therapeutic eyelid hygiene in demodicosis, computer vision syndrome, and after LASIK were 14,623 RUB and 9,200 RUB (savings of 37 %, 17,630 RUB and 9,200 RUB (savings of 47 %, 4,425.5 RUB and 3,004 RUB (savings of 32 %, respectively. Analysis of economic burden with respect to disease occurrence and typical management costs demonstrated that in 2015 this parameter was estimated as 576,198,416,556 RUB. In terms of direct medical costs, therapeutic eyelid hygiene saves 44

  8. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Kim, John J; Buchbinder, Nathan; Ammanuel, Simon; Kim, Robert; Moore, Erika; O'Donnell, Neil; Lee, Jennifer K; Kulikowicz, Ewa; Acharya, Soumyadipta; Allen, Robert H; Lee, Ryan W; Johnston, Michael V

    2013-01-01

    Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%-50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries.

  9. Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.

    Science.gov (United States)

    Roecker, Anthony J; Cox, Christopher D; Coleman, Paul J

    2016-01-28

    Since its discovery in 1998, the orexin system, composed of two G-protein coupled receptors, orexins 1 and 2, and two neuropeptide agonists, orexins A and B, has captured the attention of the scientific community as a potential therapeutic target for the treatment of obesity, anxiety, and sleep/wake disorders. Genetic evidence in rodents, dogs, and humans was revealed between 1999 and 2000, demonstrating a causal link between dysfunction or deletion of the orexin system and narcolepsy, a disorder characterized by hypersomnolence during normal wakefulness. These findings encouraged efforts to discover agonists to treat narcolepsy and, alternatively, antagonists to treat insomnia. This perspective will focus on the discovery and development of structurally diverse orexin antagonists suitable for preclinical pharmacology studies and human clinical trials. The work described herein culminated in the 2014 FDA approval of suvorexant as a first-in-class dual orexin receptor antagonist for the treatment of insomnia.

  10. New therapeutic approaches for treatment-resistant schizophrenia: a look to the future.

    Science.gov (United States)

    Miyamoto, Seiya; Jarskog, L Fredrik; Fleischhacker, W Wolfgang

    2014-11-01

    Schizophrenia for many patients is a lifelong mental disorder with significant consequences on most functional domains. One fifth to one third of patients with schizophrenia experience persistent psychotic symptoms despite adequate trials of antipsychotic treatment, and are considered to have treatment-resistant schizophrenia (TRS). Clozapine is the only medication to demonstrate efficacy for psychotic symptoms in such patients. However, clozapine is not effective in 40%-70% of patients with TRS and it has significant limitations in terms of potentially life-threatening side effects and the associated monitoring. Accordingly, a number of pharmacological and non-pharmacological biological approaches for clozapine-resistant TRS have emerged. This article provides a brief updated critical review of recent therapeutic strategies for TRS, particularly for clozapine-resistant TRS, which include pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation.

  11. A gamma-ray therapeutic system applied to treatment of body tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Yu; DUAN Zheng-Cheng; ZHU Guo-Li; GONG Shi-Hua; LI Xiao-Ping

    2004-01-01

    In order to treat malignant tumors in human body, a stereotactic gamma-ray whole-body therapeutic system has been developed. This system is a typical large mechatronics treatment machine. In this paper, its main working principles and characteristics are introduced. This system comprises a special gallows frame with an open vertical structure, a changeable collimator device by which the size of convergence center can be chosen, and a 3D treatment couch. A computer brings the couch to target position automatically. Therefore precise and dynamic rotary converging therapy for tumors located anywhere in the body has been realized. The system's performance has been proved in practice, which includes good curative effect, reliable automation, and safe and secure operation.

  12. Potential Therapeutic Mechanisms and Tracking of Transplanted Stem Cells: Implications for Stroke Treatment.

    Science.gov (United States)

    Zhang, Yanhong; Yao, Honghong

    2017-01-01

    Stem cell therapy is a promising potential therapeutic strategy to treat cerebral ischemia in preclinical and clinical trials. Currently proposed treatments for stroke employing stem cells include the replacement of lost neurons and integration into the existing host circuitry, the release of growth factors to support and promote endogenous repair processes, and the secretion of extracellular vesicles containing proteins, noncoding RNA, or DNA to regulate gene expression in recipient cells and achieve immunomodulation. Progress has been made to elucidate the precise mechanisms underlying stem cell therapy and the homing, migration, distribution, and differentiation of transplanted stem cells in vivo using various imaging modalities. Noninvasive and safe tracer agents with high sensitivity and image resolution must be combined with long-term monitoring using imaging technology to determine the optimal therapy for stroke in terms of administration route, dosage, and timing. This review discusses potential therapeutic mechanisms of stem cell transplantation for the treatment of stroke and the limitations of current therapies. Methods to label transplanted cells and existing imaging systems for stem cell labeling and in vivo tracking will also be discussed.

  13. [The multimodal interdisciplinary therapeutic program in chronic back pain. A new treatment strategy].

    Science.gov (United States)

    Casser, H; Riedel, T; Schrembs, C; Ingenhorst, A; Kühnau, D

    1999-11-01

    The epidemic-like rise in chronic low back pain in western industrial nations is less an expression of a medical than a psychosocial phenomenon. Differentiation between acute, chronic or chronifying pain is of crucial importance for therapeutic procedures. Pain syndromes in the muscular-skeletal system tend to become chronic to a far larger extent than expected. More than 80 % of low back pain represents a functional pain syndrome and does not show any pathoanatomical correlate. Pain existing independently seems to be predestined by a somatic and psychosocial deconditioning syndrome. Those at risk of chronifying pain or those whose pain is already chronic should be given an interdisciplinary, multimodal therapeutic program. A pilot study was carried out in our clinic: multidisciplinary treatment was given to our patients (of which over 90 % belonged to stages II and III on the Gerbershagen scale) and the result was significant improvement in the measurements of pain intensity, sensoric and affective pain perception, their list of complaints, the common scale of depression and the pain disability index. Taking previously published studies into consideration, it is safe to say that a multidisciplinary, multimodal program of therapy even after stay in hospital results in considerable relief of pain and improvement in the ability to cope with the pain for patients with chronified pain syndromes in the muscular-skeletal system which are resistant to treatment on an outpatient basis.

  14. [Therapeutic effect and mechanism of the surgical treatment for cervical vertigo with cervical spondylosis].

    Science.gov (United States)

    Zhong, Zhuolin; Hu, Jianhua; Zhai, Jiliang; Tian, Ye; Qiu, Guixing; Weng, Xisheng; Wu, Gui; Zhu, Qiankun; Zhao, Lijuan

    2015-07-07

    To investigate the therapeutic effect and mechanism of the surgical treatment for cervical vertigo with cervical spondylosis. Thirty-five patients in Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College, who received surgical treatment for cervical spondylosis concomitant with cervical vertigo from 2004 to 2013 were reviewed retrospectively. The preoperative cervical curvature index (CCI), slip distance and intervertebral angle, as well as the pre-and-postoperative Cobb angle were measured. The pre-and-postoperative degree of vertigo was reported according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium standard. The therapeutic effect and mechanism for patients with different imaging features and thus underwent various surgical approaches were analyzed. The mean follow-up was 40.6 months. Cervical instability was found in 33 patients. 29 of 35 (82.9%) patients had a satisfied recovery from cervical vertigo. The difference in Cobb angle in pre- and postoperative neutral cervical X-ray images was positively associated with the improvement for the vertigo (Pearson's test, P vertigo in the context of cervical spondylosis. Cervical sympathetic nerves may have played an important role in the cervical vertigo. Surgery may relieve the cervical vertigo accompanying the cervical spondylosis.

  15. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    Marzena Ciechomska

    2016-01-01

    Full Text Available Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient’s functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.

  16. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases.

    Science.gov (United States)

    Ciechomska, Marzena; O'Reilly, Steven

    2016-01-01

    Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.

  17. Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder.

    Science.gov (United States)

    Papakostas, G I; Ionescu, D F

    2015-10-01

    Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments--especially for treatment-resistant depression (TRD)--are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.

  18. Therapeutic Progression in Abused Women Following a Drug-Addiction Treatment Program.

    Science.gov (United States)

    Fernández-Montalvo, Javier; López-Goñi, José J; Arteaga, Alfonso; Cacho, Raúl; Azanza, Paula

    2015-06-30

    This study explored the prevalence of victims of abuse and the therapeutic progression among women who sought treatment for drug addiction. A sample of 180 addicted Spanish women was assessed. Information was collected on the patients' lifetime history of abuse (psychological, physical, and/or sexual), socio-demographic factors, consumption variables, and psychological symptoms. Of the total sample, 74.4% (n = 134) of the addicted women had been victims of abuse. Psychological abuse affected 66.1% (n = 119) of the patients, followed by physical abuse (51.7%; n = 93) and sexual abuse (31.7%; n = 57). Compared with patients who had not been abused, the addicted women with histories of victimization scored significantly higher on several European version of the Addiction Severity Index (EuropASI) and psychological variables. Specifically, physical abuse and sexual abuse were related to higher levels of severity of addiction. Regarding therapeutic progression, the highest rate of dropout was observed among victims of sexual abuse (63.5%; n = 33), followed by victims of physical abuse (48.9%; n = 23). Multivariate analysis showed that medical and family areas of the EuropASI, as well as violence problems and suicide ideation, were the main variables related to physical and/or sexual abuse. Moreover, women without abuse and with fewer family problems presented the higher probability of treatment completion. The implications of these results for further research and clinical practice are discussed.

  19. Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis.

    Science.gov (United States)

    Guptill, Jeffrey T; Soni, Madhu; Meriggioli, Matthew N

    2016-01-01

    Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

  20. Epigenetics: A novel therapeutic approach for the treatment of Alzheimer’s disease

    Science.gov (United States)

    Adwan, Lina; Zawia, Nasser H.

    2013-01-01

    Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field. PMID:23562602

  1. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Misra, Monika

    2013-03-01

    Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

  2. Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Guang-Biao Huang; Soo-Hyun Park; Eun-Ock Park; Eun-Kyung Choi; Young-Chul Chung; Tong Zhao; Sushma Shrestha Muna; Hong-Mei Jin; Jong-Il Park; Kyu-Sik Jo; Bo-Hee Lee; Soo-Wan Chae; Sun-Young Kim

    2013-01-01

    Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aβ)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aβ25 35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.

  3. RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.

    Science.gov (United States)

    Gonzalez-Rodriguez, Agueda; Valverde, Angela M

    2015-01-01

    RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a direct translation to medicine. The liver has been widely chosen as a model system for the development of RNA interference therapy due to the convenience and availability of effective delivery into this tissue. Numerous preclinical models have revealed promising results, but the safety of this technology remains the primary challenge in developing siRNA based treatments. Liver diseases comprise a broad spectrum of genetic and non-genetic pathologies including acute fulminant liver injury that demands urgent medical care, or chronic pathologies such as nonalcoholic fatty liver (NAFLD), alcoholic liver disease, liver cirrhosis, viral hepatitis and hepatocellular carcinoma (HCC). In some cases restoration of liver function is not possible and alternatives to liver transplantation offering novel and efficient therapeutic approaches are urgently needed. In this review, we describe recent insights on the advantages of using RNA interference in preclinical settings as a targeted strategy with potential to markedly improve the treatment of liver diseases.

  4. Target Acquired: Progress and Promise of Targeted Therapeutics in the Treatment of Prostate Cancer.

    Science.gov (United States)

    Stuchbery, Ryan; Kurganovs, Natalie J; McCoy, Patrick J; Nelson, Colleen C; Hayes, Vanessa M; Corcoran, Niall M; Hovens, Christopher M

    2015-01-01

    Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient's disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

  5. Evolving Refractory Major Depressive Disorder Diagnostic and Treatment Paradigms: Toward Closed-Loop Therapeutics

    Science.gov (United States)

    Ward, Matthew P.; Irazoqui, Pedro P.

    2010-01-01

    Current antidepressant therapies do not effectively control or cure depressive symptoms. Pharmaceutical therapies altogether fail to address an estimated 4 million Americans who suffer from a recurrent and severe treatment-resistant form of depression known as refractory major depressive disorder. Subjective diagnostic schemes, differing manifestations of the disorder, and antidepressant treatments with limited theoretical bases each contribute to the general lack of therapeutic efficacy and differing levels of treatment resistance in the refractory population. Stimulation-based therapies, such as vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation, are promising treatment alternatives for this treatment-resistant subset of patients, but are plagued with inconsistent reports of efficacy and variable side effects. Many of these problems stem from the unknown mechanisms of depressive disorder pathogenesis, which prevents the development of treatments that target the specific underlying causes of the disorder. Other problems likely arise due to the non-specific stimulation of various limbic and paralimbic structures in an open-loop configuration. This review critically assesses current literature on depressive disorder diagnostic methodologies, treatment schemes, and pathogenesis in order to emphasize the need for more stringent depressive disorder classifications, quantifiable biological markers that are suitable for objective diagnoses, and alternative closed-loop treatment options tailored to well-defined forms of the disorder. A closed-loop neurostimulation device design framework is proposed, utilizing symptom-linked biomarker abnormalities as control points for initiating and terminating a corrective electrical stimulus which is autonomously optimized for correcting the magnitude and direction of observed biomarker abnormality. PMID:20631824

  6. Evolving refractory major depressive disorder diagnostic and treatment paradigms: toward closed-loop therapeutics.

    Science.gov (United States)

    Ward, Matthew P; Irazoqui, Pedro P

    2010-01-01

    Current antidepressant therapies do not effectively control or cure depressive symptoms. Pharmaceutical therapies altogether fail to address an estimated 4 million Americans who suffer from a recurrent and severe treatment-resistant form of depression known as refractory major depressive disorder. Subjective diagnostic schemes, differing manifestations of the disorder, and antidepressant treatments with limited theoretical bases each contribute to the general lack of therapeutic efficacy and differing levels of treatment resistance in the refractory population. Stimulation-based therapies, such as vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation, are promising treatment alternatives for this treatment-resistant subset of patients, but are plagued with inconsistent reports of efficacy and variable side effects. Many of these problems stem from the unknown mechanisms of depressive disorder pathogenesis, which prevents the development of treatments that target the specific underlying causes of the disorder. Other problems likely arise due to the non-specific stimulation of various limbic and paralimbic structures in an open-loop configuration. This review critically assesses current literature on depressive disorder diagnostic methodologies, treatment schemes, and pathogenesis in order to emphasize the need for more stringent depressive disorder classifications, quantifiable biological markers that are suitable for objective diagnoses, and alternative closed-loop treatment options tailored to well-defined forms of the disorder. A closed-loop neurostimulation device design framework is proposed, utilizing symptom-linked biomarker abnormalities as control points for initiating and terminating a corrective electrical stimulus which is autonomously optimized for correcting the magnitude and direction of observed biomarker abnormality.

  7. The Genus Aloe: Phytochemistry and Therapeutic Uses Including Treatments for Gastrointestinal Conditions and Chronic Inflammation.

    Science.gov (United States)

    Cock, I E

    2015-01-01

    Plants of the genus Aloe have perhaps the longest recorded history of medicinal usage and are amongst the most widely used plants for traditional medicinal purposes worldwide. Aloe vera, Aloe ferox, Aloe arborescens and Aloe perryi are the best known and most widely used, but many other species are also used for their therapeutic properties. The Aloes have been used since ancient times, particularly for the treatment of microbial infections, gastrointestinal disorders and inflammatory conditions. In addition to their myriad uses in traditional therapeutics, the Aloes have also been used as components of cosmetic formulations, and in the food and beverage industries. Despite their wide acceptance, studies from different laboratories often report wide variations in the therapeutic bioactivities from within the same Aloe species, even when the same extraction procedures are used. Furthermore, leaves from individual Aloe plants within the same species may have widely varying levels of the bioactive phytochemicals. Phytochemical analyses have shown that many Aloe species contain various carbohydrate polymers (notably glucomannans) and a range of other low molecular weight phenolic compounds including alkaloids, anthraquinones, anthrones, benzene and furan derivatives, chromones, coumarins, flavonoids, phytosterols, pyrans and pyrones. There has been a wealth of information published about the phytochemistry and therapeutic potential of the Aloes (especially Aloe vera). Much of this has been contradictory. Intra- and interspecies differences in the redox state of the individual Aloe components and in the ratios of these components may occur between individual plants. These factors may all affect the physiological properties of Aloe extracts. Due to the structure and chemical nature of many of the Aloe phytochemicals, it is likely that many of the reported medicinal properties are due to antioxidant or prooxidant effects. The antioxidant/prooxidant activities of many Aloe

  8. Mind the gap: In-session silences are associated with client attachment insecurity, therapeutic alliance, and treatment outcome

    DEFF Research Database (Denmark)

    Daniel, Sarah Ingrid Franksdatter; Folke, Sofie; Lunn, Susanne

    2017-01-01

    Objective: The association between in-session silences and client attachment, therapeutic alliance, and treatment outcome was investigated in two treatments for bulimia nervosa. Method: 69 women and one man were randomized to two years of psychoanalytic psychotherapy (PPT) or 20 sessions of cogni......Objective: The association between in-session silences and client attachment, therapeutic alliance, and treatment outcome was investigated in two treatments for bulimia nervosa. Method: 69 women and one man were randomized to two years of psychoanalytic psychotherapy (PPT) or 20 sessions...

  9. Therapeutic community drug treatment success in Peru: a follow-up outcome study

    Directory of Open Access Journals (Sweden)

    Browne Thom

    2008-12-01

    Full Text Available Abstract Background The purpose of this study was to assess the impact of drug abuse treatment in Peru that used the therapeutic community (TC model. Program directors and several staff members from all study treatment facilities received two to eight weeks of in-country training on how to implement the TC treatment model prior to the follow-up study. Methods This outcome study involved 33 TC treatment facilities and 509 former clients in Lima and other cities in five providences across Peru. A retrospective pre-test (RPT follow-up design was employed in which 30-day use of illegal drugs and alcohol to intoxication was measured at baseline retrospectively, at the same time of the six-month follow-up. In-person interview data were collected from directors of 73 percent of the eligible TC organizations in January and February 2003 and from former 58 percent of the eligible TC former clients between October 2003 and October 2004. Drug testing was conducted on a small sample of former clients to increase the accuracy of the self-reported drug use data. Results Medium to large positive treatment effects were found when comparing 30-day illegal drug and alcohol use to intoxication before and six months after receiving treatment. As a supplemental analysis, we assumed the 42 percent of the former clients who were not interviewed at the six month assessment had returned to drugs. These results showed medium treatment effects as well. Hierarchical Generalized Linear Modeling (HGLM results showed higher implementation fidelity, less stigma after leaving treatment, and older clients, singly or in combination are key predictors of treatment success. Conclusion This study found that former clients of drug and alcohol treatment in facilities using the TC model reported substantial positive change in use of illegal drugs and alcohol to intoxication at a six-month follow-up. The unique contribution of this study is that the results also suggest attention should

  10. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  11. Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention.

    Science.gov (United States)

    Tzialla, Chryssoula; Borghesi, Alessandro; Pozzi, Margherita; Stronati, Mauro

    2015-12-07

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units. The benefits of antibiotic therapy when indicated are clearly enormous, but the continued and widespread use of antibiotics has generated over the years a strong selective pressure on microorganisms, favoring the emergence of resistant strains. Health agencies worldwide are galvanizing attention toward antibiotic resistance in gram-positive and gram-negative bacteria. Infections in neonatal units due to multidrug and extensively multidrug resistant bacteria are rising and are already seriously challenging antibiotic treatment options. While there is a growing choice of agents against multi-resistant gram-positive bacteria, new options for multi-resistant gram-negative bacteria in the clinical practice have decreased significantly in the last 20 years making the treatment of infections caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment options are currently limited and will be some years before any new treatment for neonates become available for clinical use, if ever. The aim of the review is to highlight the current knowledge on antibiotic resistance in the neonatal population, the possible therapeutic choices, and the prevention strategies to adopt in order to reduce the emergency and spread of resistant strains.

  12. THERAPEUTIC EFFECTS OF A COGNITIVE-BEHAVIOURAL TREATMENT WITH JUVENILE OFFENDERS

    Directory of Open Access Journals (Sweden)

    Antonio Andrés-Pueyo

    2012-07-01

    Full Text Available Several treatment evaluations have highlighted the effectiveness of cognitive-behavioural programmes with both youth and adult offenders. This paper describes the application and assessment of a cognitive-behavioural treatment (adapted to Spanish from Ross and Fabiano’s Reasoning & Rehabilitation Programme with juvenile offenders serving community orders in an educational measure called in Spanish ‘libertad vigilada’ (similar to parole. The intervention comprised six different therapeutic components: self-control, cognitive restructuring, problem solving, social skills/assertiveness, values/empathy, and relapse prevention. Treatment effectiveness was tested using a quasi-experimental design involving two groups and pre/post evaluation. The results show that the programme was effective (with low to moderate effect sizes in improving participants’ social skills and self-esteem, as well as in reducing their aggressiveness. However, the intervention had no positive influence on empathy, cognitive distortions or impulsiveness. These results are in line with those of many other correctional studies, in which the treatment applied had a significant but partial effect on participants.

  13. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  14. Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies

    Science.gov (United States)

    Bonsu, Kwadwo Osei; Owusu, Isaac Kofi; Buabeng, Kwame Ohene; Reidpath, Daniel Diamond; Kadirvelu, Amudha

    2016-01-01

    Heart failure (HF) is a major public health priority due to its epidemiological transition and the world’s aging population. HF is typified by continuous loss of contractile function with reduced, normal, or preserved ejection fraction, elevated vascular resistance, fluid and autonomic imbalance, and ventricular dilatation. Despite considerable advances in the treatment of HF over the past few decades, mortality remains substantial. Pharmacological treatments including β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists have been proven to prolong the survival of patients with HF. However, there are still instances where patients remain symptomatic, despite optimal use of existing therapeutic agents. This understanding that patients with chronic HF progress into advanced stages despite receiving optimal treatment has increased the quest for alternatives, exploring the roles of additional pathways that contribute to the development and progression of HF. Several pharmacological targets associated with pathogenesis of HF have been identified and novel therapies have emerged. In this work, we review recent evidence from proposed mechanisms to the outcomes of experimental and clinical studies of the novel pharmacological agents that have emerged for the treatment of HF. PMID:27350750

  15. Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics.

    Science.gov (United States)

    de Sousa, Rafael T; Zanetti, Marcus V; Brunoni, Andre R; Machado-Vieira, Rodrigo

    2015-01-01

    Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords "treatment-resistant depression", "major depressive disorder", "adjunctive", "refractory" and "augmentation". From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted.

  16. Therapeutic Effect Observation on Treatment of Vestibular Central Balance Disturbance with Brain-Regulating Electroacupuncture

    Institute of Scientific and Technical Information of China (English)

    赵宏; 刘志顺; 赵婷; 赵因; 王麟鹏; 韩丑萍

    2006-01-01

    Objective:To investigate the therapeutic effect of electroacupuncture on vestibular central balance disturbance. Methods: Forty-six patients with vestibular central balance disturbance were randomly divided into a treatment group of 23 cases and a control group of 23 cases. After 4 weeks 'treatment, the effects were evaluated by Berg balance scale, Visual analog scale and a staticdynamic balance test. Results: The effective rate was 87.0% in the treatment group and 65.2% in the control group. There was a significant difference (P< 0.05). After treatment, Berg balance scale score, eye opening with two feet standing time and eye closure with two feet standing time were better in the treatment group than in the control group after treatment (P< 0.05). Conclusion: This therapy is effective for vestibular central balance disturbance.%目的:观察电针治疗前庭中枢性平衡障碍的疗效.方法:将46例前庭中枢性平衡障碍的患者随机分为治疗组23例,对照组23例,经治疗4星期后,分别对Berg平衡量表、目测类比评分、静动态平衡试验进行观察.结果:治疗组有效率87.0%,对照组65.2%,差异有显著意义(P<0.05);疗后Berg量表积分、睁眼双足站立时间和闭眼双足站立时间,治疗组优于对照组(P<0.05).结论:该疗法是治疗前庭中枢性平衡障碍的有效方法.

  17. Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

    Science.gov (United States)

    de Quervain, Dominique J-F; Margraf, Jürgen

    2008-04-07

    Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of

  18. Differential effectiveness of residential versus outpatient aftercare for parolees from prison-based therapeutic community treatment programs

    OpenAIRE

    Messina Nena P; Prendergast Michael L; Dang Jeff; Burdon William M; Farabee David

    2007-01-01

    Abstract Background Research has indicated that more intense treatment is associated with better outcomes among clients who are appropriately matched to treatment intensity level based on the severity of their drug/alcohol problem. This study examined the differential effectiveness of community-based residential and outpatient treatment attended by male and female drug-involved parolees from prison-based therapeutic community substance abuse treatment programs based on the severity of their d...

  19. Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment.

    Science.gov (United States)

    Coler, Rhea N; Bertholet, Sylvie; Pine, Samuel O; Orr, Mark T; Reese, Valerie; Windish, Hillarie Plessner; Davis, Charles; Kahn, Maria; Baldwin, Susan L; Reed, Steven G

    2013-04-15

    Recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. The aim of this study was to assess whether therapeutic immunization could impact the course of Mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, ID93, formulated in a synthetic nanoemulsion adjuvant, GLA-SE, administered in combination with existing first-line chemotherapeutics rifampicin and isoniazid. We used a mouse model of fatal tuberculosis and the established cynomolgus monkey model to design an immuno-chemotherapeutic strategy to increase long-term survival and reduce bacterial burden, compared with standard antibiotic chemotherapy alone. This combined approach induced robust and durable pluripotent antigen-specific T helper-1-type immune responses, decreased bacterial burden, reduced the duration of conventional chemotherapy required for survival, and decreased M. tuberculosis-induced lung pathology, compared with chemotherapy alone. These results demonstrate the ability of therapeutic immunization to significantly enhance the efficacy of chemotherapy against tuberculosis and other infectious diseases, with implications for treatment duration, patient compliance, and more optimal resource allocation.

  20. Evidence for the endothelin system as an emerging therapeutic target for the treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Smith TP

    2014-08-01

    Full Text Available Terika P Smith,1 Tami Haymond,1 Sherika N Smith,1 Sarah M Sweitzer1,2 1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA; 2Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Many people worldwide suffer from pain and a portion of these sufferers are diagnosed with a chronic pain condition. The management of chronic pain continues to be a challenge, and despite taking prescribed medication for pain, patients continue to have pain of moderate severity. Current pain therapies are often inadequate, with side effects that limit medication adherence. There is a need to identify novel therapeutic targets for the management of chronic pain. One potential candidate for the treatment of chronic pain is therapies aimed at modulating the vasoactive peptide endothelin-1. In addition to vasoactive properties, endothelin-1 has been implicated in pain transmission in both humans and animal models of nociception. Endothelin-1 directly activates nociceptors and potentiates the effect of other algogens, including capsaicin, formalin, and arachidonic acid. In addition, endothelin-1 has been shown to be involved in inflammatory pain, cancer pain, neuropathic pain, diabetic neuropathy, and pain associated with sickle cell disease. Therefore, endothelin-1 may prove a novel therapeutic target for the relief of many types of chronic pain. Keywords: endothelin-1, acute pain, chronic pain, endothelin receptor antagonists

  1. OBSERVATION OF THERAPEUTIC EFFECT ON TREATMENT OF THE GREATER OCCIPITAL NEURALGIA WITH ACUPUNCTURE

    Institute of Scientific and Technical Information of China (English)

    LIU Xue-qi; LIU Wei

    2006-01-01

    Objective: To compare the differences in therapeutic effects on treatments of the greater occipital neuralgia between acupuncture and western medicine. Method: Sixty cases of the greater occipital neuralgia were randomized into acupuncture group (30 cases) and western medicine group (30 cases). In acupuncture group, acupuncture was applied on Fengchi (风池 GB 20), Chengling (承灵 GB 18), Xuanzhong (悬钟 GB 39) and Ashi (阿是穴), once everyday. In western medicine group, carbamazepine was administrated orally, 100 mg, Bid × 10 days. Results: In acupuncture group, 25 cases (83.3%) were cured, 4 cases (13.3%) remarkably effective, 1 case (3.4%) effective and 0 case ineffective. In western medicine group, 16 cases (53.3%) were cured, 7 cases (23.3%) remarkably effective, 2 cases (6.7%) effective and 5 cases ( 16.7 % ) ineffective. The cured-markedly effective rates of two groups were 96.6 % and 76.6 % respectively, indicating significant difference between two groups ( P < 0.05). Conclusion: The therapeutic effect with acupuncture on the greater occipital neuralgia was significant compared with that with carbamazepine.

  2. THE ROLE OF THERAPEUTIC SWIMMING AND KINETOPROPHYLAXY IN THE TREATMENT OF KYPHOTIC ATTITUDES

    Directory of Open Access Journals (Sweden)

    Şalgău Silviu

    2015-10-01

    Full Text Available By kinetoprophylaxy and therapeutic swimming (not restrictively and a good education of a correct posture, kyphotic attitudes can be prevented and/or eliminated, so as to contribute to the increase and harmonious development of the young generation. All these measures may give good results, but they should also endeavour to maintain their health, paying attention to their posture and sitting correctly during classes.Considering that these cases are increasingly frequent, we have focused on studying and investigating the treatment for this disease which is found in different environments, due to different causes. The conducted research set as its main objective to assess the extent to which basic kinetoprophylaxy and therapeutic swimming, associated with patient’s awareness of the need to maintain a correct attitude will lead to rebalancing the tone of the imbalanced muscle groups and which result in deficient attitudes.Obviously, in order to achieve such an objective, it was necessary to pass through a series of secondary objectives, such as: Examining and evaluating a larger number of children, in order to identify those who reported kyphotic attitudes due to muscle imbalances;Identifying the most effective ways in which we can achieve awareness and practice the correct position for children. Hypotheses: It is assumed that, the use of means of kinetoprophylaxy, with subjects presenting kyphotic attitudes due to muscle imbalances, can cause muscle tone rebalancing and attitude correction. It is assumed that, associating kinetoprophylaxy with therapeutic swimming and with posture awareness and control, may contribute to correcting the deficient attitude, and, thus, to preventing any shortcomings in the spinal column.Conclusions:The exercises to correct kyphotic attitudes, properly adapted and performed, within the framework of a consistent program, determine the functional rebalancing of the groups muscle on the front and back of the torso and

  3. Therapeutic Plasmapheresis Enabling Radioactive Iodine Treatment in a Patient with Thyrotoxicosis.

    Science.gov (United States)

    Min, Se Hee; Phung, Anita; Oh, Tae Jung; Han, Kyou-Sup; Kim, Man Jin; Kim, Jee Min; Lee, Ji Hyun; Park, Young Joo

    2015-10-01

    Therapeutic plasma exchange (TPE) is one possible treatment for patients resistant to conventional antithyroid drugs or requiring urgent attention for thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately attributed to Graves' disease in whom antithyroid drug used initially was soon discontinued, due to abnormal liver function, and replaced by Lugol's solution. Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal type machine resulted in diminished levels of thyroid hormone levels, which then rebounded after another two courses of membrane filtration type TPE. However, the patient could be treated with radioactive iodine therapy without any complications at present.

  4. Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.

    Science.gov (United States)

    Kintzing, James R; Filsinger Interrante, Maria V; Cochran, Jennifer R

    2016-12-01

    Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity. In this review we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    Science.gov (United States)

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic.

  6. Therapeutic Plasmapheresis. A Gate to an Effective Treatment of Severe Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Claudia Stefanutti

    2014-07-01

        Table 1. Different clinical use of conventional and selective apheresis techniques in relation to the pathology to be treated in emergency or on long (chronic-term.  Throughout the acute phase of hyperlipidemic pancreatitis (HLP, PEX (Lipid-apheresis could be of considerable assistance not only in lowering TG levels but also in the prevention of recurrent HLP (3. Furthermore, patients with homo-, double- compound-, and heterozygous Familial Hypercholesterolemia and HyperLp(a lipoproteinemia would benefit lipoprotein-apheresis (LA as an extracorporeal procedure providing selective removal of lipids and lipoproteins including Low Density Lipoproteins (LDL and other apolipoprotein B100-containing lipoproteins (4, 5. Having numerous metabolic and clinical superiorities, LA characterizes an upgraded selective form of conventional extracorporeal therapies, e.g. plasma-exchange (PEX- Lipid-apheresis, which were broadly-used for managing severe hypercholesterolemia in the seventies. However, LA is primarily used in the treatment of previously-mentioned severe forms of dyslipidemia. FH patients are particularly prone to coronary ischemic events necessitating a tailored, intensive, efficient, continuous, and unceasing form of treatment. Obviously, a therapeutic approach exclusively relying on existing accessible medications would not lead to preferred clinical outcomes. The above reported clinical examples clearly suggest what differences exist between the non-selective and selective apheresis techniques as far as different pathologies exhibiting affinity are concerned. In particular, the clinical presentation, emergency or not, greatly affects the use of a given extracorporeal technique. However, depending upon the indication, a selective technique not usually utilized in emergency, such as selective dextran sulfate cellulose LA was recently suggested to treat acutely preeclampsia, where targeted therapies to stabilize the clinical manifestations and prolong

  7. OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPOINT-INJECTION FOR TREATMENT OF GOUTY ARTHRITIS

    Institute of Scientific and Technical Information of China (English)

    曾振秀; 林文清

    2001-01-01

    In the present paper, 60 cases of gouty arthritis patients were randomly divided into acupuncture group (n=30) and acupoint-injection group (n=30). In these two groups, the tender-point was used as the main acupoint, combined with Taichong (LR 3), Yinbai (SP 1), Sanyinjiao (SP 6), Juegu (GB 39), Xuehai (SP 10), etc. 10 % Chishao (Radix Paeoniae Rubra) Injection and dexamethasone were used for acupoint-injection. Results indicated that in acupoint-injeution and acupuncture groups, 15 (50.0%) and 9 (30.0%) cases had marked improvement, 12 (40.0%) and 10 (33.3%) were effective, and 3 (10.0%) and 11(36.7%) failed in treatment, with the total effective rats being 90.0 % and 63.3 % respectively. Statistical analysis shows that acupoint-injection is significantly superior to simple acupuncture in the therapeutic effect ( P<0.05)

  8. Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer.

    Science.gov (United States)

    Hervault, Aziliz; Thanh, Nguyen Th Kim

    2014-10-21

    Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

  9. Vagus nerve stimulation may be a sound therapeutic option in the treatment of refractory epilepsy

    Directory of Open Access Journals (Sweden)

    Murilo S. Meneses

    2013-01-01

    Full Text Available INTRODUCTION: Refractory epilepsy accounts for 20 to 30% of epilepsy cases and remains a challenge for neurologists. Vagus nerve stimulation (VNS is an option for palliative treatment. OBJECTIVE: It was to study the efficacy and tolerability of VNS in patients implanted with a stimulator at the Curitiba Institute of Neurology (INC. METHODS: A case study of six patients with refractory epilepsy submitted to a VNS procedure at the INC in the last four years was described and discussed. RESULTS: Mean age at time of implantation was 29 years. Mean follow-up was 26.6 months. Seizure frequency decreased in all patients (40-50% (n=2 and >80% (n=4. Three patients no longer required frequent hospitalizations. Two patients previously restricted to wheelchairs started to walk, probably because of improved mood. CONCLUSION: In this population, VNS proved to be a sound therapeutic option for treating refractory epilepsy.

  10. [Xenogeneic cell therapeutics: Treatment of type 1 diabetes using porcine pancreatic islets and islet cells].

    Science.gov (United States)

    Godehardt, Antonia W; Schilling-Leiß, Dagmar; Sanzenbacher, Ralf; Tönjes, Ralf R

    2015-11-01

    In view of the existing shortage of human donor organs and tissues, xenogeneic cell therapeutics (xCT) offer an alternative for adequate treatment. In particular, porcine pancreatic islets and islet cells have already entered the field of experimental therapy for type-1 diabetes mellitus (T1DM) patients. Thereby, xCT depict challenging products with a glance on medical, ethical, and regulatory questions. With cross-species transplantation (xenotransplantation), the risk of immunological graft rejection as well as the risk of infectious transmission of microbial and viral pathogens must be considered. This includes the bidirectional transmission of microorganisms from graft to host as well as from host to graft. Crossing the border of species requires a critical risk-benefit evaluation as well as a thorough longtime surveillance of transplant recipients after treatment. The international legal and regulatory requirements for xCT are inter alia based on the World Health Organization criteria summarized in the Changsha Communiqué (2008). In the European Union, they were reflected by the European Medicines Agency (EMA) Guideline on Xenogeneic Cell-based Medicinal Products following the implementation of the Regulation on Advanced Therapies (ATMP). On the basis of this regulation, the first non-clinical and clinical experiences were obtained for porcine islets. The results suggest that supportive treatment of T1DM risk patients with xCT may be an alternative to established allogeneic organ transplantation in the future.

  11. MDMA and PTSD treatment: "PTSD: From novel pathophysiology to innovative therapeutics".

    Science.gov (United States)

    Sessa, Ben

    2017-05-10

    There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment-resistant PTSD. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  12. The recent updates of therapeutic approaches against aβ for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Ling, Shucai; Zhou, Jing; Rudd, John A; Hu, Zhiying; Fang, Marong

    2011-08-01

    One of the main neuropathological lesions observed in brain autopsy of Alzheimer's disease (AD) patients is the extracellular senile plaques mainly composed of amyloid-beta (Aβ) peptide. Recently, treatment strategies have focused on modifying the formation, clearance, and accumulation of this potentially neurotoxic peptide. β- and γ-secretase are responsible for the cleavage of amyloid precursor protein (APP) and the generation of Aβ peptide. Treatments targeting these two critical secretases may therefore reduce Aβ peptide levels and positive impact on AD. Vaccination is also an advanced approach against Aβ. This review focuses on recent advances of our understanding of this key peptide, with emphasis on Aβ peptide synthesis, accumulation and neurotoxicity, and current therapies including vaccination and two critical secretase inhibitors. MicroRNAs (miRNAs) are a class of conserved endogenous small noncoding RNAs, known to regulate the expression of complementary messenger RNAs, involved in AD development. We therefore address the relationship of miRNAs in the brain and Aβ generation, as a novel therapeutic approach to the treatment of AD while also providing new insights on the etiology of this neurological disorder.

  13. Therapeutic Effect of Propofol in the Treatment of Endotoxin-induced Shock in Rats

    Institute of Scientific and Technical Information of China (English)

    高巨; 曾邦雄; 周罗晶; 袁世荧; 张诗海

    2003-01-01

    To assess the potential therapeutic effect of propofol in the treatment of endotoxemia, 76rats were randomly assigned to 5 groups: control group(A), endotoxemic group(B), pre-treatmentgroup(C), simultaneous treatment group(D) and post-treatment group(E). Five h after endotoxininjection, PO2, pH, MAP, plasma concentrations of Nitrite/nitrate (NO2-/NO3-) and mortalityrates were assessed in each group. After the rats were sacrificed, lung tissue was sampled to meas-ure myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-α contents. It was foundthat endotoxin injection produced progressive hypotension, metabolic acidosis, and a large increasein the plasma NO2-/NO3- concentrations and increased mortality rates in 5h. Endotoxin injectionsignificantly increased MPO activity and TNF-α contents in lung tissue (P< 0. 01 or P < 0. 05 ).These changes response to endotoxin were significantly attenuated in the groups B, C and D. Butthese beneficial effects were blunted in the group E. The results suggest that propofol administra-tion may offer advantages in endotoxemia.

  14. THERAPEUTIC EFFECT OF NON-SURGICAL TREATMENT OF CHRONIC PERIODONTITIS IN DIABETIC CHINESE

    Institute of Scientific and Technical Information of China (English)

    YANG Yun-zhu(杨芸珠); SUN Zhe(孙喆); HU Chun-zhen(胡纯贞); YANG Yu-guo(杨裕国); JIN Li-jian(金力坚); LEUNG Hui-qiang(梁惠强); Esmond F Corbet

    2004-01-01

    Objective To observe the therapeutic effect of non-surgical treatment on diabetic Chinese with chronic periodontitis. Methods Moderate to advanced chronic periodontitis (CP) was studied in 36 diabetes mellitus (DM) patients classified as 20 with high and fiuctuating blood glucose level (DM-H) and 16 with relatively low and stable blood glucose level (DM-L). 28 non-DM CP patients acted as controls (Non-DM). Plaque index (PH), gingival index (Gl), bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (AL)of all patients were recorded at 6 sites on each tooth at the baseline and 1,3 and 6 months after oral hygiene instruction ( OHI) , scaling and root planing. Results It was found that the short-term effect of non-surgical periodontal procedure had resulted in significant resolution of gingival inflammation and pronounced reduction in pocket depth and gain of attachment loss in both DM and Non-DM CP patients. Conclusion The pilot study suggested that non-surgical periodontal treatment allowed for favorable treatment responses in a group of Chinese diabetic subjects with chronic periodontitis and that their various profiles of blood glucose did not influence the short-term healing response to OHI, scaling and root planning.

  15. Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections

    Directory of Open Access Journals (Sweden)

    Marina Berditsch

    2016-09-01

    Full Text Available An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix® paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20–40 min at a concentration of 40–80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100–200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication.

  16. Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections

    Science.gov (United States)

    Berditsch, Marina; Lux, Hannah; Babii, Oleg; Afonin, Sergii; Ulrich, Anne S.

    2016-01-01

    An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix® paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20–40 min at a concentration of 40–80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100–200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication. PMID:27618065

  17. Manual therapy and therapeutic exercise in the treatment of osteoarthritis of the hip: a systematic review

    Directory of Open Access Journals (Sweden)

    A. Romeo

    2013-05-01

    Full Text Available This systematic review aimed at investigating the role of therapeutic exercise and/or manual therapy in the treatment of hip osteoarthritis (OA. Two independent reviewers (AR, CV searched PubMed, Cinahl, Cochrane Library, PEDro and Scopus databases and a third one (SP was consulted in case of disagreement. The research criteria were publication period (from May 2007 to April 2012 and publication language (English or Italian. Ten randomized controlled trials matched inclusion criteria, eight of which concerning therapeutic exercise and two manual therapy. Few good quality studies were found. At mid- and long-term follow-up land-based exercises showed insufficient evidence of effectiveness with respect to pain and quality of life, but positive results were found for physical function. Water exercises significantly reduced fall risk when combined with functional exercises. Programs containing progressive and gradual exposure of difficult activities, education and exercises promoted better outcomes, higher adherence to home program and increased amount of physical activity, especially walking. Manual therapy seemed to reduce pain and decrease disability at short-term. Less use of nonsteroidal anti-inflammatory drugs was statistically significant at long-term follow-up in patients treated with manual therapy. The relationship between clinical results and radiological grade of OA was not investigated. Encouraging results were found in recent literature for manual therapy and functional training. Further research is needed to elucidate this issue through high-quality trials, especially addressing the aspects that have not been thoroughly explored yet, for instance type, amount and scheduling of conservative treatment.

  18. Marburg virus infection in nonhuman primates: Therapeutic treatment by lipid-encapsulated siRNA.

    Science.gov (United States)

    Thi, Emily P; Mire, Chad E; Ursic-Bedoya, Raul; Geisbert, Joan B; Lee, Amy C H; Agans, Krystle N; Robbins, Marjorie; Deer, Daniel J; Fenton, Karla A; MacLachlan, Ian; Geisbert, Thomas W

    2014-08-20

    Marburg virus (MARV) and the closely related filovirus Ebola virus cause severe and often fatal hemorrhagic fever (HF) in humans and nonhuman primates with mortality rates up to 90%. There are no vaccines or drugs approved for human use, and no postexposure treatment has completely protected nonhuman primates against MARV-Angola, the strain associated with the highest rate of mortality in naturally occurring human outbreaks. Studies performed with other MARV strains assessed candidate treatments at times shortly after virus exposure, before signs of disease are detectable. We assessed the efficacy of lipid nanoparticle (LNP) delivery of anti-MARV nucleoprotein (NP)-targeting small interfering RNA (siRNA) at several time points after virus exposure, including after the onset of detectable disease in a uniformly lethal nonhuman primate model of MARV-Angola HF. Twenty-one rhesus monkeys were challenged with a lethal dose of MARV-Angola. Sixteen of these animals were treated with LNP containing anti-MARV NP siRNA beginning at 30 to 45 min, 1 day, 2 days, or 3 days after virus challenge. All 16 macaques that received LNP-encapsulated anti-MARV NP siRNA survived infection, whereas the untreated or mock-treated control subjects succumbed to disease between days 7 and 9 after infection. These results represent the successful demonstration of therapeutic anti-MARV-Angola efficacy in nonhuman primates and highlight the substantial impact of an LNP-delivered siRNA therapeutic as a countermeasure against this highly lethal human disease.

  19. Developing a Therapeutic Range of Adalimumab Serum Concentrations in Management of Psoriasis: A Step Toward Personalized Treatment

    NARCIS (Netherlands)

    Menting, S.P.; Coussens, E.; Pouw, M.F.; Reek, J.M.P.A. van den; Temmerman, L.; Boonen, H.; Jong, E.M.G.J. de; Spuls, P.I.; Lambert, J.

    2015-01-01

    IMPORTANCE: Adalimumab has proven to be effective in suppressing psoriasis disease activity and is administered in a standard dose. OBJECTIVE: To establish a therapeutic range for adalimumab trough levels in the treatment of plaque-type psoriasis, leading to a more personalized treatment. DESIGN, SE

  20. A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes.

    Science.gov (United States)

    Silverman, K; Svikis, D; Robles, E; Stitzer, M L; Bigelow, G E

    2001-02-01

    This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In this treatment, patients are paid to perform jobs or to participate in job training. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Pregnant and postpartum drug abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants were invited to work 3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for abstinence, workplace attendance, and performance. On average, 45% of participants attended the workplace per day. Relative to controls, the Therapeutic Workplace nearly doubled patients' abstinence from opiates and cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively, p Workplace can effectively treat heroin and cocaine abuse in pregnant and postpartum women.

  1. Autophagy blockade enhances HDAC inhibitors' pro-apoptotic effects: Potential implications for the treatment of a therapeutic-resistant malignancy

    OpenAIRE

    Lopez, Gonzalo; Torres, Keila; Lev, Dina

    2011-01-01

    Malignant peripheral nerve sheath tumors (MPNST s) are aggressive, highly metastatic, poor prognosis tumors for which effective therapeutic strategies are currently lacking. We summarize recent work focusing on preclinical evaluation of histone deacetylase inhibitors (HDACis) for the treatment of MPNST. HDACis are a novel drug class with anti-cancer therapeutic promise. Using human MPNST cell lines and xenograft models we found that a MPNST subset is highly sensitive to HDACis, whereas a frac...

  2. The therapeutic community for addicts : intimacy, perent involvment and treatment outcome

    NARCIS (Netherlands)

    M. Kooyman (Martien)

    1992-01-01

    textabstractTherapeutic communities for addicts developed since the Sixties without a clear theory on what made them therapeutic. There have also been some doubts on their long term outcome results. Part I of this book describes how therapeutic communities for addicts have roots in the self-help mov

  3. The therapeutic community for addicts : intimacy, perent involvment and treatment outcome

    NARCIS (Netherlands)

    M. Kooyman (Martien)

    1992-01-01

    textabstractTherapeutic communities for addicts developed since the Sixties without a clear theory on what made them therapeutic. There have also been some doubts on their long term outcome results. Part I of this book describes how therapeutic communities for addicts have roots in the self-help

  4. The therapeutic community for addicts : intimacy, perent involvment and treatment outcome

    NARCIS (Netherlands)

    M. Kooyman (Martien)

    1992-01-01

    textabstractTherapeutic communities for addicts developed since the Sixties without a clear theory on what made them therapeutic. There have also been some doubts on their long term outcome results. Part I of this book describes how therapeutic communities for addicts have roots in the self-help mov

  5. CLINICAL OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE PLUS MANUAL REPOSITION FOR TREATMENT OF ACUTE LUMBAR VERTEBRAL ARTICULAR DYSKINESIA

    Institute of Scientific and Technical Information of China (English)

    骆钧梵

    2003-01-01

    Objective: To observe the therapeutic effect of acupuncture plus manual reposition for treatment of acute lumbar vertebral articular dyskinesia for choosing a better remedy. Methods: 66 cases of acute lumbar vertebral articular dyskinesia were randomly divided into acupuncture plus manual reposition group (treatment group, n= 33) and routine manual reposition group (control group, n = 33). Yaotong-point was punctured, when, the patient was asked to move his or her waist simultaneously. Results: After one session of treatment, of the two 33 cases in treatment and control groups, 28 (84.85%) and20 (60.61%) were cured, 4 (12.12%) and 9 (27.27%) were improved, and 1 (3.03%) and 4 (12.12%) failed in the treatment. The therapeutic effect of treatment group was significantly superior to that of control group ( P< 0.05). Conclusion: Acupuncture combined with manual reposition is apparently superior to simple routine manual reposition in relieving acute lumbar vertebral articular dyskinesia.

  6. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    failure, due to bacteria with coexistent macrolide-associated and fluoroquinolone-associated resistance mutations, were recently published by Australian investigators. Pristinamycin and solithromycin may be of clinical benefit for such multidrug-resistant infections. Further clinical studies are required to determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. Keywords: Mycoplasma genitalium, non-gonococcal urethritis, macrolide, fluoroquinolone, resistance, treatment failure

  7. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Paola Savoia

    2015-09-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer in individuals with fair skin type (I–II and steadily increasing in incidence (70% of skin malignancy. It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC.

  8. Therapeutic effect of bone cement injection in the treatment of intraosseous ganglion of the carpal bones.

    Science.gov (United States)

    Yu, Kunlun; Shao, Xinzhong; Tian, Dehu; Bai, Jiangbo; Zhang, Bing; Zhang, Yingze

    2016-09-01

    The aim of the present study was to treat intraosseous ganglia of the carpal bones with injectable bone cement grafting. Between January 2012 and December 2013, 4 patients (3 men and 1 woman) presenting with wrist pain and activity limitation were diagnosed with intraosseous ganglion of the carpal bones by radiography. The patients were treated with minimal invasive curettage and bone cement injection surgery. All patients were followed up for a mean time of 17 months (range, 12-22 months). The wrist pain was significantly reduced in all patients following surgery. In addition, the activity range and grip strength were also improved compared with the preoperative parameters. Subsequent to treatment, the Mayo wrist score and the Disabilities of the Arm, Shoulder and Hand score presented mean values of 78.8 (range, 75-80) and 11 (range, 7.7-15.0), respectively. These results suggested that the patients showed a good recovery. All patients were satisfied with the postoperative results and returned to work within 4 weeks. In conclusion, bone cement injection is an effective and safe therapeutic strategy for the treatment of intraosseous ganglia of the carpal bone.

  9. Predicting therapeutic response to secondary treatment with bupropion: dichotic listening tests of functional brain asymmetry.

    Science.gov (United States)

    Bruder, Gerard E; Stewart, Jonathan W; Schaller, Jennifer D; McGrath, Patrick J

    2007-10-31

    Studies using neuroimaging, electrophysiologic and cognitive measures have raised hopes for developing predictors of therapeutic response to antidepressants. Pretreatment measures of functional brain asymmetry have been found to be related to response to the selective serotonin reuptake inhibitor fluoxetine. This report examines the extent to which dichotic listening tests also predict clinical response to an antidepressant with a different mechanism of action, i.e., bupropion. Dichotic listening data were obtained for 17 unmedicated depressed patients who were subsequently treated with bupropion. Right-handed outpatients were tested on dichotic fused-words and complex-tones tests. Seven patients who responded to bupropion and 10 nonresponders did not differ in gender, age or education. Bupropion responders had significantly larger left-hemisphere advantage for perceiving words when compared to nonresponders, but there was no difference in their right-hemisphere advantage for tones. All patients having a left-hemisphere advantage above the normal mean responded to bupropion, whereas only 9% of patients below the normal mean responded to treatment. These findings should encourage further study of the clinical value of dichotic listening and other measures of functional brain asymmetry for identifying depressed patients who most benefit from treatment with different classes of antidepressants.

  10. Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Raskin, Philip

    2013-07-01

    Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.

  11. Combination of treatment with death receptor 5-specific antibody with therapeutic HPV DNA vaccination generates enhanced therapeutic anti-tumor effects.

    Science.gov (United States)

    Tseng, Chih Wen; Monie, Archana; Trimble, Cornelia; Alvarez, Ronald D; Huh, Warner K; Buchsbaum, Donald J; Straughn, J Michael; Wang, Mei-Cheng; Yagita, Hideo; Hung, Chien-Fu; Wu, T-C

    2008-08-12

    There is currently a vital need for the development of novel therapeutic strategies for the control of advanced stage cancers. Antigen-specific immunotherapy and the employment of antibodies against the death receptor 5 (DR5) have emerged as two potentially promising strategies for cancer treatment. In the current study, we hypothesize that the combination of treatment with the anti-DR5 monoclonal antibody, MD5-1 with a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7(detox)) administered via gene gun would lead to further enhancement of E7-specific immune responses as well as anti-tumor effects. Our results indicated that mice bearing the E7-expressing tumor, TC-1 treated with MD5-1 monoclonal antibody followed by CRT/E7(detox) DNA vaccination generated the most potent therapeutic anti-tumor effects as well as highest levels of E7-specific CD8+ T cells among all the groups tested. In addition, treatment with MD5-1 monoclonal antibody was capable of rendering the TC-1 tumor cells more susceptible to lysis by E7-specific cytotoxic T lymphocytes. Our findings serve as an important foundation for future clinical translation.

  12. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Allen RH

    2013-01-01

    Full Text Available John J Kim,1,2 Nathan Buchbinder,1,† Simon Ammanuel,1,4,5,† Robert Kim,1,† Erika Moore,1 Neil O'Donnell,1 Jennifer K Lee,3 Ewa Kulikowicz,3 Soumyadipta Acharya,1 Robert H Allen,1,9 Ryan W Lee,6,7 Michael V Johnston4–81Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, 2The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, 3Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, 4Kennedy Krieger Institute, 5Hugo W Moser Research Institute, 6Department of Neurology, 7Department of Pediatrics, 8Department of Physical Medicine and Rehabilitation Johns Hopkins University School of Medicine, Baltimore, MD; 9Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA†These authors contributed equally to this workAbstract: Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE. Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors

  13. Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer.

    Science.gov (United States)

    Morad, Samy A F; Davis, Traci S; MacDougall, Matthew R; Tan, Su-Fern; Feith, David J; Desai, Dhimant H; Amin, Shantu G; Kester, Mark; Loughran, Thomas P; Cabot, Myles C

    2017-04-15

    The anticancer properties of ceramide, a sphingolipid with potent tumor-suppressor properties, can be dampened via glycosylation, notably in multidrug resistance wherein ceramide glycosylation is characteristically elevated. Earlier works using the ceramide analog, C6-ceramide, demonstrated that the antiestrogen tamoxifen, a first generation P-glycoprotein (P-gp) inhibitor, blocked C6-ceramide glycosylation and magnified apoptotic responses. The present investigation was undertaken with the goal of discovering non-anti-estrogenic alternatives to tamoxifen that could be employed as adjuvants for improving the efficacy of ceramide-centric therapeutics in treatment of cancer. Herein we demonstrate that the tamoxifen metabolites, desmethyltamoxifen and didesmethyltamoxifen, and specific, high-affinity P-gp inhibitors, tariquidar and zosuquidar, synergistically enhanced C6-ceramide cytotoxicity in multidrug resistant HL-60/VCR acute myelogenous leukemia (AML) cells, whereas the selective estrogen receptor antagonist, fulvestrant, was ineffective. Active C6-ceramide-adjuvant combinations elicited mitochondrial ROS production and cytochrome c release, and induced apoptosis. Cytotoxicity was mitigated by introduction of antioxidant. Effective adjuvants markedly inhibited C6-ceramide glycosylation as well as conversion to sphingomyelin. Active regimens were also effective in KG-1a cells, a leukemia stem cell-like line, and in LoVo human colorectal cancer cells, a solid tumor model. In summary, our work details discovery of the link between P-gp inhibitors and the regulation and potentiation of ceramide metabolism in a pro-apoptotic direction in cancer cells. Given the active properties of these adjuvants in synergizing with C6-ceramide, independent of drug resistance status, stemness, or cancer type, our results suggest that the C6-ceramide-containing regimens could provide alternative, promising therapeutic direction, in addition to finding novel, off-label applications

  14. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    Science.gov (United States)

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  15. Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication.

    Science.gov (United States)

    Xu, Yongpeng; Wang, Shuo; Jiang, Lulu; Wang, Hui; Yang, Yilin; Li, Ming; Wang, Xujing; Zhao, Xiulan; Xie, Keqin

    2016-01-01

    1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenousantioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1-BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1-BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin.We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect.

  16. Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia

    Directory of Open Access Journals (Sweden)

    Hajheydari Zohreh

    2009-01-01

    Full Text Available Background: Finasteride, a type P-selective 5a-reductase inhibitor, as a causative agent of decreasing dihydroxy testestrone (DHT level, is effective in the treatment of male androgenic alopecia. Aim: We compared the local and oral finasteride in the treatment of androgenic alopecia. Method: This is a double blind, randomized clinical trial study of 45 male patients, who were referred with alopecia to the private clinics and departments in Boo-Ali Sina Hospital, in Sari. Patients with male androgenic alopecia were selected according to the history and physical examinations. The patients were randomly divided into two: topical finasteride (A and oral finasteride (B groups. Topical finasteride group (A received a topical gel of 1% finasteride and placebo tablets, while the oral finasteride group (B received finasteride tablets (1 mg and gel base (without drug as placebo for 6 months. The patients were followed by clinical observation and recording of side effects prior to the treatment and at the end of first week, and then by a monthly follow-up. The size of bald area, total hair count, and terminal hair were studied. Data were analyzed by descriptive and Chi-square statistical test. Results: The mean duration of hair loss was 18.8±23.10 months. Each month the terminal hair, size of bald area and hair count between the two groups were compared. There were no significant differences between the two groups as a viewpoint of hair thickness, hair counts and the size of bald area. Serial measurements indicated a significant increase in hair counts and terminal hair counts between the two groups. Conclusions: The results of this study showed that the therapeutic effects of both finasteride gel and finasteride tablet were relatively similar to each other.

  17. The Potential Therapeutic Effect of Green Tea in Treatment of Vernal Keratoconjunctivitis

    Directory of Open Access Journals (Sweden)

    Mahnaz Mosallaei

    2008-05-01

    Full Text Available Vernal keratoconjunctivitis is a chronic, recurrent and severe ocular allergic disease, which is characterized by persistent allergic inflammation of the conjunctiva. It can be accompanied by ocular discomfort and visual disturbance. All forms are characterized by intense itching, tearing, mucous secretions and a severe photophobia, which often forces children to live virtually in dark places. Conjunctival proliferative changes, such as the formation of giant papillae are the characteristic findings of affected individuals. Giant papillae develop as a result of infiltration of inflammatory cells, changes in the epithelial layer, and increased deposition of extracellular matrix molecules such as collagen and proliferation of conjunctival fibroblasts. Currently several therapeutic options such as corticosteroids, mast cell stabilizers and cyclosporine are applied for treatment of Vernal keratoconjunctivitis but in long-term, the chronic and recurrent nature of this problem leads to failure or appearance of side effects of current treatment in many patients. Recently, Green tea extract and its principal active ingredient, epigallocatechin gallate , are gaining attention and increased usage due to its healthful properties. It has considerable anticatactogenic effect by inducing apoptosis in lens epithelial cells and antioxidant effects. Also its great benefits were achieved in attenuation of damaging influences to the retina caused by ischemia/reperfusion. Based on evidences supported beneficial effects of green tea, we hypothesize that local administration of green tea and its extract seems to be a proper substitute or adjunct to current treatments of Vernal keratoconjunctivitis. This plant contains a series of antioxidants that can abolish the process of allergic cascade. Moreover, by suppressing TNF-alpha potentially, it can reduce proinflammatory reaction, as well as fibroblast proliferation and subsequently decrease giant papilla formation

  18. Disposition kinetics of selenium in healthy volunteers following therapeutic shampoo treatment.

    Science.gov (United States)

    Noisel, Nolwenn; Bouchard, Michèle; Carrier, Gaétan

    2010-05-01

    This study was aimed at documenting the kinetic time courses of selenium (Se) in accessible biological matrices of volunteers following controlled applications of therapeutic shampoo containing Se, to better elucidate the mechanisms by which shampoo-Se accumulates in hair and hence estimate the contribution of this source to total Se body burden. Ten healthy volunteers were exposed to Se-shampoo three times a week over a month. Blood, hair and toenail concentrations along with daily urinary excretions were repeatedly measured over an 18-month period following the onset of application. Over the entire study period, blood concentrations of Se (range: 127-233μg/l) and daily urinary excretions (range: 11.9-150μg/d) remained within baseline range of the general population. Conversely, during shampoo application, mean Se concentrations in hair reached transitional levels of 89μg/g while, following cessation of treatment, a mono-exponential decrease was observed with a mean half-life of 4.5 weeks. Two of the volunteers also exhibited an increase in toenail concentrations of Se during the study period. Results show that Se-shampoo does not contribute significantly to total Se body burden, as assessed from blood and urine levels. Differences observed between blood and urine time courses as compared to hair profiles and the presence of Se on hair grown before treatment indicates an adsorption on hair; however, the gradual decrease in Se concentrations in successive centimeters of hair grown following the application period suggests a concomitant absorption from the scalp during treatment with subsequent excretion in hair.

  19. Therapeutic Observation on Treatment of Infantile Cerebral Palsy with Integrative Chinese-Western Medicine: A Clinical Report of 104 Cases

    Institute of Scientific and Technical Information of China (English)

    XU Dong-hao; SHI Bing-pei; SHI Wei; CHEN Dong-dong; MIAO Jing; YANG Hong; HAN Chou-ping

    2007-01-01

    Objective: To study the therapeutic effects of combined treatment with Chinese and western medicine in children with cerebral palsy (CP). Methods: 104 CP children were treated mainly with physiotherapy and acupuncture, together with occupational therapy, sensory integration and electrical stimulation. Gross Motor Function Measure (GMFM) was used to assess the effects of treatment. Results: After treatment for 3.29±0.80 months, the majority of CP children improved their IQ and limb symptoms, with decreased abnormal posture, increased muscle strength and improved motor developmental function. GMFM88 and GMFM66 scores had significantly increased after treatment. Conclusions: Combined treatment with Chinese and Western Medicine has confirmed effects on CP children.

  20. Early Therapeutic Alliance, Treatment Retention, and 12-Month Outcomes in a Healthy Lifestyles Intervention for People with Psychotic Disorders.

    Science.gov (United States)

    Andrews, Michelle; Baker, Amanda L; Halpin, Sean A; Lewin, Terry J; Richmond, Robyn; Kay-Lambkin, Frances J; Filia, Sacha L; Castle, David; Williams, Jill M; Clark, Vanessa; Callister, Robin

    2016-12-01

    Engaging and retaining individuals with psychotic disorders in psychosocial treatments is difficult. Early therapeutic alliance, treatment retention, and 12-month outcomes were examined in a subsample of smokers with a psychotic disorder (N = 178) participating in a healthy lifestyles study comparing a telephone versus face-to-face delivered intervention. Therapeutic alliance was assessed using the Agnew Relationship Measure; primary outcomes were treatment retention and changes in symptoms and health behaviors. Contrary to expectations, early alliance did not predict treatment retention. However, elements of both client- and therapist-rated alliance predicted some clinical outcomes (e.g., higher confidence in the therapeutic alliance at session 1 predicted improvements in 12-month depression). Some modest interactions between early alliance and intervention condition were also identified (e.g., clients initially with lower self-perceived initiative, or higher therapist-perceived bonding benefited preferentially from the telephone-delivered intervention), highlighting the need to further examine the interplay between therapeutic alliance and treatment modality.

  1. InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

    Science.gov (United States)

    Rushforth, Dominic P; Pratt, Brenda E; Chittenden, Sarah J; Murray, Iain S; Causer, Louise; Grey, Matthew J; Gear, Jonathan I; Du, Yong; Flux, Glenn D

    2017-03-01

    The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration.

  2. Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases.

    Science.gov (United States)

    Shimokawa, Hiroaki

    2002-03-01

    Rho-kinase has been identified as one of the effectors of the small GTP-binding protein Rho. Accumulating evidence has demonstrated that the Rho/Rho-kinase-mediated pathway plays an important role in various cellular functions, not only in vascular smooth muscle contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions, all of which may be involved in the pathogenesis of arteriosclerosis/atherosclerosis. Indeed, animal experiments have demonstrated that Rho-kinase inhibitors effectively suppress coronary artery spasm and that long-term inhibition of Rho-kinase inhibits the development of coronary arteriosclerotic lesions and even causes regression of coronary vascular lesions in vivo. Recent clinical studies also have demonstrated the inhibitory effect of a Rho-kinase inhibitor on coronary artery spasm in patients with vasospastic angina and on exercise-induced myocardial ischemia in patients with stable effort angina with adequate safety. It is possible that Rho-kinase is also involved in the pathogenesis of other forms of cardiovascular diseases. Thus, Rho-kinase could be regarded as a novel therapeutic target in treatment of cardiovascular diseases.

  3. Role of curcumin in idiopathic pulmonary arterial hypertension treatment: a new therapeutic possibility.

    Science.gov (United States)

    Bronte, Enrico; Coppola, Giuseppe; Di Miceli, Riccardo; Sucato, Vincenzo; Russo, Antonio; Novo, Salvatore

    2013-11-01

    The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include systemic drugs such as prostanoids, phosphodiesterase inhibitors and antagonists of endothelin-1 (ERBs). Some researchers have long investigated the anti-inflammatory effects of curcumin. It shows a role for inactivation of NF-κB-mediated inflammation. On the basis of these findings we propose a potential role of curcumin and its pharmacologically fit derivatives for treatment of idiopathic pulmonary arterial hypertension.

  4. Current therapeutic leads for the treatment of melanoma: targeted immunotherapy in the post-genomic era.

    Science.gov (United States)

    Papanastasiou, Anastasios D; Sirinian, Chaido; Kalofonos, Haralabos P; Repanti, Maria

    2014-01-01

    Metastatic melanoma has a poor prognosis and until today most therapeutic approaches are ineffective. Advances in molecular pathology and genome analysis technologies have led to the identification of genetic events and immune regulatory checkpoints that provide novel targets for pharmaceutical intervention in melanoma. Development of selective mitogen-activated kinase (MAPK) pathway inhibitors was the first major achievement coming from genetic studies that identified a constitutively active MAP kinase pathway and BRAF activating mutations in melanoma. At the same time, the manipulation of immune system checkpoints through monoclonal antibodies changed clinical practice and led to further improvement of patient outcomes. In an effort to further develop melanoma targeted therapies that depend on the genetic profile of a given patient, high-throughput genome wide approaches (next-generation sequencing [NGS], gene arrays, etc) have been employed for the characterization of genetic alterations in the patient's tumor. In the near future, the combined information from the genetic and immune background of an individual will provide the basis for a personalized, highly targeted approach in the treatment of melanoma.

  5. Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus.

    Science.gov (United States)

    Yoshimoto, Ryo; Miyamoto, Yasuhisa; Shimamura, Ken; Ishihara, Akane; Takahashi, Kazuhiko; Kotani, Hidehito; Chen, Airu S; Chen, Howard Y; Macneil, Douglas J; Kanatani, Akio; Tokita, Shigeru

    2006-09-12

    Histamine H3 receptors (H3Rs) are located on the presynaptic membranes and cell soma of histamine neurons, where they negatively regulate the synthesis and release of histamine. In addition, H3Rs are also located on nonhistaminergic neurons, acting as heteroreceptors to regulate the releases of other amines such as dopamine, serotonin, and norepinephrine. The present study investigated the effects of H3R ligands on appetite and body-weight regulation by using WT and H3R-deficient mice (H3RKO), because brain histamine plays a pivotal role in energy homeostasis. The results showed that thioperamide, an H3R inverse agonist, increases, whereas imetit, an H3R agonist, decreases appetite and body weight in diet-induced obese (DiO) WT mice. Moreover, in DiO WT mice, but not in DiO H3RKO mice, imetit reduced fat mass, plasma concentrations of leptin and insulin, and hepatic triglyceride content. The anorexigenic effects of imetit were associated with a reduction in histamine release, but a comparable reduction in histamine release with alpha-fluoromethylhistidine, an inhibitor of histamine synthesis, increased appetite. Moreover, the anorexigenic effects of imetit were independent of the melanocortin system, because imetit comparably reduced appetite in melanocortin 3 and 4 receptor-deficient mice. The results provide roles of H3Rs in energy homeostasis and suggest a therapeutic potential for H3R agonists in the treatment of obesity and diabetes mellitus.

  6. Zika virus outbreak: an overview of the experimental therapeutics and treatment.

    Science.gov (United States)

    Saxena, Shailendra K; Elahi, Asif; Gadugu, Srinivasulu; Prasad, Anil K

    2016-06-01

    Zika virus (ZIKV) infection is a new emerging threat around the globe which might be responsible for microcephaly and Guillain-Barre syndrome in the infants. Recently, ZIKV outbreak has caused a public health crisis in Brazil after being linked to a sharp increase in birth defects. ZIKV is ssRNA virus belongs to the family Flaviviridae. It is mainly transmitted by mosquito bite specifically Aedes species and disease symptoms include fever, joint pain, muscle pain, rash, conjunctivitis, and headache. The reservoir of ZIKV is still not known. Protection at personal level by avoiding mosquito bite would help to reduce the incidence of the disease. Control of ZIKV infection by vaccination or antiviral drug either from modern, complementary and alternative medicines may be considered to be one of the most effective strategies in the long run. Large scale immunization of susceptible human population is highly required to prevent this deadly disease. Attempts should be made as soon as possible to develop effective vaccines or antiviral to prevent ZIKV infection. This article provides a current overview of the experimental therapeutics and treatment options based on modern, complementary and alternative medicines.

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

    Science.gov (United States)

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

    2010-02-01

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

  8. Sclerostin inhibition: a novel therapeutic approach in the treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Shah AD

    2015-06-01

    Full Text Available Arti D Shah,1 Dolores Shoback,1,2 E Michael Lewiecki3,4 1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; 2Endocrine Research Unit, Department of Medicine, Veterans Affairs Medical Center, San Francisco, CA, USA; 3University of New Mexico School of Medicine, Albuquerque, NM, USA; 4New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA Abstract: Osteoporosis and osteoporosis-related fractures are growing problems with the aging population and are associated with significant morbidity and mortality. At this time, other than parathyroid hormone analogs, all therapies for osteoporosis are antiresorptive. Therefore, researchers have focused efforts on development of more anabolic therapies. Understanding of the Wnt signaling pathway, which is critical for skeletal development, and the role of sclerostin in inhibition of Wnt signaling has led to the discovery of a novel therapeutic approach in the treatment of osteoporosis – sclerostin inhibition. In this review, we discuss the biology of Wnt signaling and sclerostin inhibition. We then discuss human disorders of decreased sclerostin function and animal models of sclerostin inhibition. Both have served to elucidate the effects of decreased sclerostin levels and function – increased bone mass and strength and fewer fractures. In addition, we review data from Phase I and II studies of the two humanized sclerostin monoclonal antibodies, romosozumab and blosozumab, both of which have had positive effects on bone mineral density. We conclude with a discussion of the ongoing Phase III studies of romosozumab. The available data support the potential for neutralizing sclerostin monoclonal antibodies to serve as anabolic agents in the treatment of osteoporosis. Keywords: osteoporosis, sclerostin, Wnt signaling, anabolic therapies, romosozumab 

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

    Directory of Open Access Journals (Sweden)

    Guang-Huan Sun

    2010-10-01

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

  10. Oral zinc sulphate in treatment of patients with thallium poisoning: A clinical therapeutic trial

    Directory of Open Access Journals (Sweden)

    Ahmed A. Al-Mohammadi

    2011-06-01

    Full Text Available Thallium poisoning is usually associated with typical dermatological features simulating that of zinc deficiency. The aim of this study was to evaluate the role of oral zinc sulphate in the treatment of patients with thallium poisoning.Materials and methods: This clinical therapeutic trial study was conducted in Departments of Dermatology of Baghdad and Basrah Teaching Hospitals from February 2008 - February 2010, where a total of 37 patients with thallium poisoning were enrolled.A detailed history was taken from all patients and complete clinical examination was performed. All patients received zinc sulphate in a dose of 5 mg/kg three times a day few days before confirming the diagnosis of thallium poisoning. Thallium in urine had been measured using the colorimetric method and was positive in all patients. After confirming the diagnosis of thallium poisoning, thallium antidotes Prussian blue was given to 32 patients.Results: Age range of 37 patients was 5-33 (24±5.3 years. The dermatological findings were mainly: anagen hair loss affected the scalp and limbs. Also, dusky ecchymotic red dermatitis like rash was observed on the face and dorsum of hands and legs, while neurological manifestations were mainly of peripheral neuropathy, were reported in 21 (55% patients. All patients but two responded promptly to a trial of zinc sulphate within few days.Conclusion: Oral Zinc sulphate appears to be an effective and safe treatment for thallium poisoning particularly for skin and hair features and in reducing its lethal progression and complications. J Clin Exp Invest 2011;2(2:133-7

  11. Current and Emerging Therapeutic Strategies for the Treatment of Meibomian Gland Dysfunction (MGD).

    Science.gov (United States)

    Thode, Adam R; Latkany, Robert A

    2015-07-01

    Meibomian gland (MG) dysfunction (MGD) is a multifactorial, chronic condition of the eyelids, leading to eye irritation, inflammation and ocular surface disease. Initial conservative therapy often includes a combination of warm compresses in addition to baby shampoo or eyelid wipes. The practice of lid hygiene dates back to the 1950s, when selenium sulfide-based shampoo was first used to treat seborrhoeic dermatitis of the eyelids. Today, tear-free baby shampoo has replaced dandruff shampoo for MGD treatment and offers symptom relief in selected patients. However, many will not achieve significant improvement on this therapy alone; some may even develop an allergy to the added dyes and fragrances in these products. Other manual and mechanical techniques to treat MGD include MG expression and massage, MG probing and LipiFlow(®). While potentially effective in patients with moderate MGD, these procedures are more invasive and may be cost prohibitive. Pharmacological treatments are another course of action. Supplements rich in omega-3 fatty acids have been shown to improve both MGD and dry eye symptoms. Tea tree oil, specifically the terpenin-4-ol component, is especially effective in treating MGD associated with Demodex mites. Topical antibiotics, such as azithromycin, or systemic antibiotics, such as doxycycline or azithromycin, can improve MGD symptoms both by altering the ocular flora and through anti-inflammatory mechanisms. Addressing and treating concurrent ocular allergy is integral to symptom management. Topical N-acetylcysteine and topical cyclosporine can both be effective therapeutic adjuncts in patients with concurrent dry eye. A short course of topical steroid may be used in some severe cases, with monitoring for steroid-induced glaucoma and cataracts. While the standard method to treat MGD is simply warm compresses and baby shampoo, a more tailored approach to address the multiple aetiologies of the disease is suggested.

  12. Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy.

    Science.gov (United States)

    Tutka, Piotr; Zatoński, Witold

    2006-01-01

    Cytisine, a natural plant alkaloid, has been marketed in Central and Eastern Europe for over 40 years for the clinical management of smoking cessation. Despite the fact that cytisine has been used by millions of smokers, its characteristics have not been reviewed in scientific literature in English, and presently existing clinical studies on its effectiveness and safety are insufficient to warrant licensing by modern standards. Understanding of the mechanism of cytisine action as a smoking cessation aid provides a necessary basis for conducting clinical trials to confirm its efficacy as an optimal antismoking therapy. Hereafter, we present a review of current knowledge about the pharmacokinetics, pharmacodynamics, toxicity, therapeutic efficacy and safety of cytisine, and about its derivatives that are under development. Recent pharmacological research has elucidated that the drug is a low efficacy partial agonist of alpha4beta2 nicotinic acetylcholine receptors, which are believed to be central to the effect of nicotine (NIC) on the reward pathway. The drug reduces the effects of NIC on dopamine release in the mesolimbic system when given alone, while simultaneously attenuating NIC withdrawal symptoms that accompany cessation attempts. Clinical studies on cytisine as a smoking cessation aid have demonstrated that the drug is effective and safe. Our recent uncontrolled trial has shown that a 12-month carbon monoxide-verified continuous abstinence rate following a standard course of treatment with cytisine with minimal behavioral support is similar (13.8%; N = 436) to that observed following treatment with NIC replacement therapy. Since cytisine exhibits a desirable pharmacological profile which makes it an attractive smoking cessation drug, it should be advanced to randomized clinical trials. However, more detailed preclinical studies on its pharmacokinetics and safety profile are required.

  13. [Therapeutic targets in the treatment of dyslipidemia: HDL and non-HDL cholesterol].

    Science.gov (United States)

    Brea Hernando, Ángel Julián

    2014-07-01

    Atherogenic dyslipidemia (AD) consists of the combination of an increase in very low density lipoproteins (VLDL), which results in increased plasma triglyceride (TG) levels, with a reduction of levels of high-density lipoprotein bound cholesterol (HDL-C), also accompanied by a high proportion of small and dense LDL particles. AD is considered the main cause of the residual risk of experiencing cardiovascular disease (CVD), which is still presented by any patient on treatment with statins despite maintaining low-density lipoprotein bound cholesterol (LDL-C) levels below the values considered to be the objective. Non-HDL cholesterol (non-HDL-c) reflects the number of atherogenic particles present in the plasma. This includes VLDL, intermediate density lipoproteins (IDL) and LDL. Non-HDL-c provides a better estimate of cardiovascular risk than LDL-c, especially in the presence of hypertriglyceridemia or AD. The European guidelines for managing dyslipidemia recommend that non-HDL-c values be less than 100 and 130 mg/dL for individuals with very high and high cardiovascular risk, respectively. However, these guidelines state that there is insufficient evidence to suggest that raising HDL-c levels incontrovertibly results in a reduction in CVD. Therefore, the guidelines do not set recommended HDL-c levels as a therapeutic objective. The guidelines, however, state that individuals with AD on treatment with statins could benefit from an additional reduction in their risk by using fibrates. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  14. Reduced chance of hearing loss associated with Therapeutic Drug Monitoring of Aminoglycosides in the treatment of Multidrug Resistant Tuberculosis

    NARCIS (Netherlands)

    van Altena, R; Dijkstra, J.A.; van der Meer, M E; Borjas Howard, J F; Kosterink, J G W; van Soolingen, D; van der Werf, T S; Alffenaar, J W C

    2017-01-01

    Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to

  15. Therapeutic Alliance and Treatment Adherence in Two Interventions for Bulimia Nervosa: A Study of Process and Outcome

    Science.gov (United States)

    Loeb, Katharine L.; Wilson, G. Terence; Labouvie, Erich; Pratt, Elizabeth M.; Hayaki, Jumi; Walsh, B. Timothy; Agras, W. Stewart; Fairburn, Christopher G.

    2005-01-01

    The relationship between therapeutic alliance, therapist adherence to treatment protocol, and outcome was analyzed in a randomized trial of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy for bulimia nervosa. Independent observers rated audiotapes of full-length therapy sessions. Purging frequency was the primary outcome…

  16. Therapeutic Alliance and Treatment Adherence in Two Interventions for Bulimia Nervosa: A Study of Process and Outcome

    Science.gov (United States)

    Loeb, Katharine L.; Wilson, G. Terence; Labouvie, Erich; Pratt, Elizabeth M.; Hayaki, Jumi; Walsh, B. Timothy; Agras, W. Stewart; Fairburn, Christopher G.

    2005-01-01

    The relationship between therapeutic alliance, therapist adherence to treatment protocol, and outcome was analyzed in a randomized trial of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy for bulimia nervosa. Independent observers rated audiotapes of full-length therapy sessions. Purging frequency was the primary outcome…

  17. How effective is pre-release nematode control in farm-reared red-legged partridges Alectoris rufa?

    Science.gov (United States)

    Villanúa, D; Pérez-Rodríguez, L; Rodríguez, O; Viñuela, J; Gortázar, C

    2007-03-01

    Game bird farming is associated with high parasite levels that reduce farm productivity, reduce survival after releasing, and may pose a health risk for natural populations. The efficacy of albendazole (orally, 20 mg kg(-1) was evaluated in farmed red-legged partridges naturally infected with the nematodes Aonchotheca caudinflata and Heterakis gallinarum. In treated birds body condition improved, nematode egg deposition was reduced and the proportion of gravid A. caudinflata females was reduced, but not the overall worm burdens. Albendazole was found to be 36.8% and 17.1% effective against A. caudinflata and H. gallinarum, respectively. These results indicate that the anthelmintic treatment used normally in Spanish partridge farms is not effective enough to avoid the introduction of parasites into the field after release.

  18. Recovery Journeys of Counselors and Clients: A Case Study of the Therapeutic Alliance in a Drug Treatment and Rehabilitation Center in Malaysia

    Science.gov (United States)

    Amat, Mohamad Isa

    2013-01-01

    The therapeutic alliance is a significant research area in counseling. The understanding of the therapeutic alliance, particularly in drug treatment settings helps counselors and clients to increase the treatment outcomes and its treatment process. The present study investigated the journeys of recovering counselors and clients in a private…

  19. Pre-treatment antinuclear antibody positivity, therapeutic efficacy and persistence of biologics in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Codreanu Cătălin

    2016-06-01

    Full Text Available Introduction: Rheumatoid factor (RF and anti-citrullinated protein antibodies (ACPA are poor prognostic factors in rheumatoid arthritis (RA. The therapeutic implication of antinuclear antibody (ANA positivity in RA is still debated. The study aims to evaluate ANA positivity as a prognostic factor for the therapeutic response to biologics in RA.

  20. Virtual reality as therapeutic tool in the confines of social anxiety disorder treatment

    DEFF Research Database (Denmark)

    Grillon, Helena; Riquier, Francoise; Herbelin, Bruno

    2006-01-01

    We hereby present a study whose aim is to evaluate the efficiency and flexibility of virtual reality as a therapeutic tool in the confines of a social phobia behavioural therapeutic program. Our research protocol, accepted by the ethical commission of the cantonal hospices’ psychiatry service...

  1. A Web-Based Therapeutic Workplace for the Treatment of Drug Addiction and Chronic Unemployment

    Science.gov (United States)

    Silverman, Kenneth; Wong, Conrad J.; Grabinski, Michael J.; Hampton, Jacqueline; Sylvest, Christine E.; Dillon, Erin M.; Wentland, R. Daniel

    2005-01-01

    This article describes a Web-based therapeutic workplace intervention designed to promote heroin and cocaine abstinence and train and employ participants as data entry operators. Patients are paid to participate in training and then to perform data entry jobs in a therapeutic workplace business. Salary is linked to abstinence by requiring patients…

  2. Therapeutic Community in a California Prison: Treatment Outcomes after 5 Years

    Science.gov (United States)

    Zhang, Sheldon X.; Roberts, Robert E. L.; McCollister, Kathryn E.

    2011-01-01

    Therapeutic communities have become increasingly popular among correctional agencies with drug-involved offenders. This quasi-experimental study followed a group of inmates who participated in a prison-based therapeutic community in a California state prison, with a comparison group of matched offenders, for more than 5 years after their initial…

  3. Virtual reality as therapeutic tool in the confines of social anxiety disorder treatment

    DEFF Research Database (Denmark)

    Grillon, Helena; Riquier, Francoise; Herbelin, Bruno

    2006-01-01

    We hereby present a study whose aim is to evaluate the efficiency and flexibility of virtual reality as a therapeutic tool in the confines of a social phobia behavioural therapeutic program. Our research protocol, accepted by the ethical commission of the cantonal hospices’ psychiatry service, is...

  4. Observation on Therapeutic Effect in Treatment of Hypoxemic Infantile Encephalopathy by Acupuncture plus Hyperbaric Oxygen

    Institute of Scientific and Technical Information of China (English)

    刘锦; 郭峰; 蒯乐

    2006-01-01

    目的:探讨针刺结合高压氧治疗小儿缺氧缺血性脑病(HIE)的疗效.方法:59例HIE患儿,分为治疗组(33例),对照组(26例),两组均采用纠正酸中毒,控制脑水肿及惊厥,静脉滴注脑活素或胞二磷胆碱等基础治疗,治疗组则采用针刺结合高压氧治疗,对照组则只采用高压氧治疗.结果:治疗组与对照组总有效率分别为97.0%,73.1%.经统计学处理P<0.01差异非常显著.结论:针刺加高压氧治疗HIE优于单用高压氧治疗,主要表现在能缩短疗程,提高治愈率,降低死亡率,减少后遗症的发生,HIE患儿应尽早治疗.%Objective: To investigate the therapeutic effect of acupuncture plus hyperbaric oxygen in treating hypoxemic infantile encephalopathy (HIE). Methods: Fifty-nine HIE children were divided into treatment (33 cases) and control (26 cases) groups. Both groups were treated by basic therapy of removing acidosis, controlling cerebral edema and convulsion, and intravenous drip of cerebrolysin or citicoline. The treatment group was treated by acupuncture plus hyperbaric oxygen and the control group was treated by hyperbaric oxygen only. Results: The total effective rate was 97.0% in the treatment group and 73.1% in the control group. Statistical analysis showed a highly significant difference (P<0.01). Conclusion: Acupuncture plus hyperbaric oxygen was better than simple hyperbaric oxygen in treating HIE. Its main manifestations were shortening the course of disease, increasing cure rate, decreasing death rate and reducing the occurrence of sequelae.HIE children should be treated as early as possible.

  5. A meta-analysis of the relation between therapeutic alliance and treatment outcome in eating disorders.

    Science.gov (United States)

    Graves, Tiffany A; Tabri, Nassim; Thompson-Brenner, Heather; Franko, Debra L; Eddy, Kamryn T; Bourion-Bedes, Stephanie; Brown, Amy; Constantino, Michael J; Flückiger, Christoph; Forsberg, Sarah; Isserlin, Leanna; Couturier, Jennifer; Paulson Karlsson, Gunilla; Mander, Johannes; Teufel, Martin; Mitchell, James E; Crosby, Ross D; Prestano, Claudia; Satir, Dana A; Simpson, Susan; Sly, Richard; Lacey, J Hubert; Stiles-Shields, Colleen; Tasca, Giorgio A; Waller, Glenn; Zaitsoff, Shannon L; Rienecke, Renee; Le Grange, Daniel; Thomas, Jennifer J

    2017-02-02

    The therapeutic alliance has demonstrated an association with favorable psychotherapeutic outcomes in the treatment of eating disorders (EDs). However, questions remain about the inter-relationships between early alliance, early symptom improvement, and treatment outcome. We conducted a meta-analysis on the relations among these constructs, and possible moderators of these relations, in psychosocial treatments for EDs. Twenty studies met inclusion criteria and supplied sufficient supplementary data. Results revealed small-to-moderate effect sizes, βs = 0.13 to 0.22 (p conducta alimentaria (TCA). Sin embargo, quedan preguntas acerca de la inter-relación entre alianza temprana, mejoría temprana de síntomas y resultados del tratamiento. Hicimos un meta-análisis de la relación entre estos constructos y los posibles moderadores de estas relaciones en los tratamientos psicosociales para TCA. Método: Veintiún estudios reunieron los criterios de inclusión y aportaron suficientes datos suplementarios. Resultados: los resultados revelaron un efecto de la talla pequeño a moderado, ฆยs = 0.13 a 0.22 (p < .05), encontrando que la mejoría temprana de los síntomas estuvo relacionada con la subsecuente calidad de la alianza y las calificaciones de la alianza también estuvieron relacionadas con la subsecuente reducción de los síntomas. La relación entre alianza temprana y resultados de tratamiento fue parcialmente explicada por la temprana mejoría de los síntomas. Con relación a los moderadores, la alianza temprana mostró débiles asociaciones con el resultado en terapias con un fuerte componente conductual relativo a terapias no conductuales. Sin embargo, la alianza mostró más fuerte relación con los resultados para pacientes más jóvenes (versus mayores), por encima y sobre la varianza compartida con la temprana mejoría de síntomas. Discusión: En resumen, la reducción temprana de los síntomas refuerza la alianza terapéutica y los

  6. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

    Science.gov (United States)

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-03-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

  7. Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria

    Science.gov (United States)

    Bell, Sean M.; Wendt, Dan J.; Zhang, Yanhong; Long, Shinong; Tsuruda, Laurie; Zhao, Bin; Laipis, Phillip; Fitzpatrick, Paul A.

    2017-01-01

    Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000), at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2) upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av) PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser), rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients. PMID:28282402

  8. [Anxiogenic and anxiolytic effects of lithium chloride under preventive and therapeutic treatments of male mice with repeated experience of aggression].

    Science.gov (United States)

    Smagin, D A; Kudryavtseva, N N

    2014-01-01

    Repeated experience of aggression in daily agonistic interactions is accompanied by development of changes in behaviors and psychoemotional states indicating the development of the psychopathology of aggressive behavior, which are difficult to correct by drugs used for decrease of aggression in the clinics. In this paper the influence of lithium chloride on the behavior of aggressive males in different tests assessing anxiety, communication and exploratory activity (elevated plus maze test, social interaction test, partition test), as well as aggressiveness (agonistic interaction test) were studied. Lithium chloride (Sigma-Aldrich Co, 100 mg/kg/day, i.p.) was administered preventively to male in ranging from the 7th day of agonistic interactions, as well as therapeutically to males with 21 days of aggression experience during the period without agonistic interactions. Also the effects of chronic lithium chloride treatment on behaviors of animals without agonistic interactions (intact mice) were studied. Period of drug and saline (as the controls) treatment--14 days. It has been shown that preventive lithium chloride treatment of male mice with repeated experience of aggression induced pronounced anxiogenic effect, under therapeutic treatment--nxiolytic effects. Anxiolytic effect was also observed in intact males. There is no effect of lithium chloride on aggression. Differences in the effects of lithium chloride under preveitive and therapeutic treatments, as well as the causes of individual sensitivity to the drug in male mice in one group were discussed.

  9. Therapeutic implications of Epstein–Barr virus infection for the treatment of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Hutajulu SH

    2014-09-01

    Full Text Available Susanna Hilda Hutajulu,1 Johan Kurnianda,1 I Bing Tan,2,3 Jaap M Middeldorp4 1Department of Internal Medicine, Faculty of Medicine Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia; 2Department of Ear, Nose and Throat, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; 3Department of Ear, Nose and Throat, Faculty of Medicine Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia; 4Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands Abstract: Nasopharyngeal carcinoma (NPC is highly endemic in certain regions including the People's Republic of China and Southeast Asia. Its etiology is unique and multifactorial, involving genetic background, epigenetic, and environment factors, including Epstein–Barr virus (EBV infection. The presence of EBV in all tumor cells, aberrant pattern of antibodies against EBV antigens in patient sera, and elevated viral DNA in patient circulation as well as nasopharyngeal site underline the role of EBV during NPC development. In NPC tumors, EBV expresses latency type II, where three EBV-encoded proteins, Epstein–Barr nuclear antigen 1, latent membrane protein 1 and 2 (LMP1, 2, are expressed along with BamH1-A rightward reading frame 1, Epstein–Barr virus-encoded small nuclear RNAs, and BamH1-A rightward transcripts. Among all encoded proteins, LMP1 plays a central role in the propagation of NPC. Standard treatment of NPC consists of radiotherapy with or without chemotherapy for early stage, concurrent chemoradiotherapy in locally advanced tumors, and palliative systemic chemotherapy in metastatic disease. However, this standard care has limitations, allowing recurrences and disease progression in a certain proportion of cases. Although the pathophysiological link and molecular process of EBV-induced oncogenesis are not fully understood, therapeutic approaches targeting the virus may increase the

  10. Pre-Release Consumption of Methyl Eugenol Increases the Mating Competitiveness of Sterile Males of the Oriental Fruit Fly, Bactrocera dorsalis, in Large Field Enclosures

    Science.gov (United States)

    Shelly, Todd E.; Edu, James; McInnis, Donald

    2010-01-01

    The sterile insect technique may be implemented to control populations of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), when environmental concerns preclude widespread use of chemical attractants or toxicants. The goal of the present study was to evaluate whether the mating competitiveness of sterile B. dorsalis males could be increased via pre-release feeding on methyl eugenol. Males of the oriental fruit fly are strongly attracted to this plant-borne compound, which they ingest and use in the synthesis of the sex pheromone. Previous studies conducted in the laboratory and small field-cages have shown that males given methyl eugenol produce a more attractive pheromone for females and have a higher mating success rate than males denied methyl eugenol. Here, levels of egg sterility were compared following the release of wild-like flies and either methyl eugenol-fed (treated) or methyl eugenol-deprived (control) sterile males in large field enclosures at four over flooding ratios ranging from 5:1 to 60:1 (sterile: wild-like males). Treated sterile males were fed methyl eugenol for 1–4 h (depending on the over flooding ratio tested) 3 d prior to release. Eggs were dissected from introduced fruits (apples), incubated in the laboratory, and scored for hatch rate. The effect of methyl eugenol was most pronounced at lower over flooding ratios. At the 5:1 and 10:1 over flooding ratios, the level of egg sterility observed for treated, sterile males was significantly greater than that observed for control, sterile males. In addition, the incidence of egg sterility reported for treated sterile males at these lower over flooding ratios was similar to that noted for treated or control sterile males at the 30:1 or 60:1 over flooding ratios. This latter result, in particular, suggests that pre-release feeding on methyl eugenol allows for a reduction in the number of sterile flies that are produced and released, thus increasing the cost

  11. 75 FR 41873 - Prospective Grant of Exclusive License: The Development of Human Therapeutics for the Treatment...

    Science.gov (United States)

    2010-07-19

    ... with Increased Affinity to CD22 Expressing Leukemia Cells'' [HHS Ref. E-129-2001/0-US- 01], US Patent... improve the therapeutic value of PE while maintaining its ability to trigger cell death. Since CD22...

  12. Therapist self-disclosure and the therapeutic alliance in the treatment of eating problems.

    Science.gov (United States)

    Simonds, Laura M; Spokes, Naomi

    2017-01-01

    Evidence is mixed regarding the potential utility of therapist self-disclosure. The current study modelled relationships between perceived helpfulness of therapist self-disclosures, therapeutic alliance, patient non-disclosure, and shame in participants (n = 120; 95% women) with a history of eating problems. Serial multiple mediator analyses provided support for a putative model connecting the perceived helpfulness of therapist self-disclosures with current eating disorder symptom severity through therapeutic alliance, patient self-disclosure, and shame. The analyses presented provide support for the contention that therapist self-disclosure, if perceived as helpful, might strengthen the therapeutic alliance. A strong therapeutic alliance, in turn, has the potential to promote patient disclosure and reduce shame and eating problems.

  13. Therapeutic plasma exchange-A new dawn in the treatment of pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar

    2015-01-01

    Full Text Available Pemphigus vulgaris is an autoimmune disorder that involves intraepithelial blistering and sores of skin and mucous membrane. It generally correlates with the levels of circulating autoantibodies; their removal seems a reasonable therapeutic approach. Therapeutic plasma exchange is hypothesized to remove pathogenic autoantibodies and has been used in refractory or severe cases. It may be considered for rapid control of severe or recalcitrant pemphigus vulgaris and should be combined with use of concomitant immuno-suppressive.

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

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

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

  15. OBSERVATIONS ON THE THERAPEUTIC EFFECT OF THE TREATMENT OF 100 SCAPULOHUMERAL PERIARTHRITIS CASES BY "HEGUCI" (MUSCLE NEEDLING) COMBINED WITH MASSAGE

    Institute of Scientific and Technical Information of China (English)

    ZHANG Gui-xiang

    2005-01-01

    Objective: To explore an effective method for managing middle and late stages of scapulohumeral periarthritis. Methods: A total of 182 cases of scapulohumeral periarthritis were randomized into treatment group (100 cases) and control group ( 82 cases); those in treatment group were managed by "Heguci" (合谷刺muscle needling) at the reactionary spot of focus (found out via palpation around the shoulder region) in combination with reinforcing needling manipulation of "Setting the Mountain on Fire" and topical massage; whereas, those in control group treated by conventional method of "selecting acupoints [Jianqian (肩前extra point), Jianyu (肩髃 LI 15), Jianliao (肩髎 TE 14), etc] along the course of the affected meridians in combination with massage". The treatment was given once daily, with 10 sessions being a therapeutic course, 20 sessions altogether. Results: Of the 100 cases and 82 cases in control and treatment groups, 36 (43.90%) and 69 (69.00%) were cured, 42 (51.21%) and 26 (26.00%) improved, 4 (4.87%) and 5 (5.00%) failed, with the total effective rates being 95.13% and 95.00% respectively. The average treatment sessions of control and treatment groups were 16.32±4.24 and 9.66±8.44 separately. The curative rate of treatment group was significantly higher than that of control group and the number of the therapeutic sessions required of the former group was evidently fewer than that of the later group (P<0.01). Conclusion: The therapeutic effect of "Heguci" combined with massage is significantly superior to that of conventional acupuncture plus massage in the treatment of middle and late stages of scapulohumeral periarthritis.

  16. Establishing a compulsory drug treatment prison: Therapeutic policy, principles, and practices in addressing offender rights and rehabilitation.

    Science.gov (United States)

    Birgden, Astrid; Grant, Luke

    2010-01-01

    A Compulsory Drug Treatment Correctional Center (CDTCC) was established in Australia in 2006 for repeat drug-related male offenders. Compulsory treatment law is inconsistent with a therapeutic jurisprudence approach. Despite the compulsory law, a normative offender rehabilitation framework has been established based on offender moral rights. Within moral rights, the offender rehabilitation framework addresses the core values of freedom (supporting autonomous decision-making) and well-being (supporting support physical, social, and psychological needs). Moral rights are underpinned by a theory or principle which, in this instance, is a humane approach to offender rehabilitation. While a law that permits offenders to choose drug treatment and rehabilitation is preferable, the article discusses the establishment of a prison based on therapeutic policy, principles, and practices that respond to participants as both rights-violators and rights-holders. The opportunity for accelerated community access and a therapeutic alliance with staff has resulted in offenders actively seeking to be ordered into compulsory drug treatment and rehabilitation.

  17. COMPARATIVE STUDY ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE AND WESTERN MEDICINES FOR TREATMENT OF PERIPHERAL FACIAL PALSY

    Institute of Scientific and Technical Information of China (English)

    陶加平; 盛薇; 彭君华

    2001-01-01

    Subjective: To observe the therapeutic effect of acupuncture in treatment of acute peripheral facial paralysis. Methods: A total of 80 cases of facial palsy were randomly divided into acupuncture group (n=50) and Western medicine (control) group (n = 30). In acupuncture group, Cuanzhu (BL 2), Sibai (ST 2), Yangbai (GB 14), etc. were punctured, combined with TDP radiation, cupping or administration of Chinese medicinal herbs according to the concrete situations. Acupuncture treatment was given once daily, with 6 days being a therapeutic course, continuously for 4 courses. In control group, patients were treated with intravenous injection of "energy mixture", dexamethasone, compound Danshen injectio, etc.. Results: After treatment, in acupuncture group, of the 50 cases, 48 were cured and 2 had improvement, with the effective rate being 100% ; among them, 12 cases were cured in 7 days, 23 cured in 8~14 days, 10 cured in 15~21 days and 3 cured in 22~28 days. In control group, of the 30 cases, 19 were cured, 8 had improvement and 3 had no apparent changes, with the effective rate being 90%. Of the 19 cured cases, 5 were cured within 8~14 days, 10 cured in 15-21 days and 4 cured in 22~28 days. Conclusion: In treatment of acute periphery facial palsy, acupuncture is obviously superior to Western medicines in the therapeutic effect and cure duration.

  18. The therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and statins for treatment of preeclampsia

    Directory of Open Access Journals (Sweden)

    Tereza eCindrova-Davies

    2014-05-01

    Full Text Available Preeclampsia is a complex multifactorial disease. Placental oxidative stress, a result of deficient spiral artery remodeling, plays an important role in the pathophysiology of preeclampsia. Antiangiogenic factors secreted from malperfused placenta are instrumental in mediating maternal endothelial dysfunction and consequent symptoms of preeclampsia; the mechanism is likely to involve increased ET-1 secretion and reduced NO bioavailability. Therapeutic interventions so far remain only experimental and there is no established remedy for the treatment of preeclampsia. This review concentrates on the evidence for the therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and statins. These compounds display pleitropic antioxidant, anti-inflammatory, and pro-angiogenic effects in animal and in vitro studies. Although clinical trials on the use of antioxidant vitamins in pregnancy proved largely unsuccessful, the scope for their use still exists given the beneficial cardioprotective effects of antioxidant-rich Mediterranean diet, periconceptual vitamin use and the synergistic effect of vitamin C and l-arginine. Encouraging clinical evidence exists for the use of NO donors, and a clinical trial is underway testing the effect of statins in treatment of preeclampsia. H2S recently emerged as a novel therapeutic agent for cardiovascular disease, and its beneficial effects were also tested in animal models of preeclampsia. It is risky to prescribe any medication to pregnant women on a large scale, and any future therapeutic intervention has to be well tested and safe. Many of the compounds discussed could be potential candidates.

  19. Routine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed Tomography-Staged Treatment-Naive Patients With Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; d´Amore, Francesco; Juul Mylam, Karen

    2012-01-01

    Routine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed Tomography-Staged Treatment-Naive Patients With Hodgkin Lymphoma......Routine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed Tomography-Staged Treatment-Naive Patients With Hodgkin Lymphoma...

  20. FRMD4A: A potential therapeutic target for the treatment of tongue squamous cell carcinoma

    Science.gov (United States)

    Zheng, Xianghuai; Jia, Bo; Lin, Xi; Han, Jiusong; Qiu, Xiaoling; Chu, Hongxing; Sun, Xiang; Hu, Weitao; Pan, Jie; Chen, Jun; Zhao, Jianjiang

    2016-01-01

    The aim of the present study was to identify agents capable of inhibiting the invasion and metastasis of tongue squamous cell carcinoma and thereby improve the outcomes of patients suffering from tongue cancer. FRMD4A antibodies were used to probe 78 paraffin-embedded specimens of tongue squamous cell carcinoma and 15 normal tongue tissues, which served as controls. Immunohistochemical methods were then used for analysis. Clinical pathological parameters were obtained, and the association between FRMD4A expression in the samples and the pathological parameters was analyzed. The human tongue cancer cell line CAL27 was used to study the effects of FRMD4A. CAL27 cells were transfected with small-interfering RNA against FRMD4A (FRMD4A-siRNA) and the mRNA and protein levels of FMRD4A were then evaluated by RT-qPCR and western blot analysis, respectively. The proliferation and cell-cycle assays of CAL27 cells were evaluated using the CCK8 method and flow cytometry. The invasion and migration of the cells were measured using a Matrigel invasion chamber and a scratch assay, respectively. The results showed FRMD4A overexpression in tongue squamous cell carcinoma, and the positive reaction was predominately located in the cytoplasm. Tumor clinical stage and lymph node metastasis showed a statistically significant correlation with FRMD4A expression. Transient silencing of the FRMD4A gene for 24 and 48 h significantly decreased the mRNA and protein expression of FRMD4A, respctively. Silencing FRMD4A gene reduced the proliferation of CAL27 cells and led to cell cycle arrest in the G1 phase, as well as significantly suppressing the migration and invasion capacity of CAL27 cells. The findings of the present study suggest that FRMD4A expression correlates with the development of tongue squamous cell carcinoma. For this reason, FRMD4A merits further study as it may be suitable for use as a therapeutic agent in antitumor treatment regimens. PMID:27666346

  1. Comparative Effectiveness of Antihypertensive Therapeutic Classes and Treatment Strategies In Initiation of Therapy In Primary Care Patients: A Distributed Ambulatory Research in Therapeutics Network (DARTNet) Study

    Science.gov (United States)

    Bronsert, Michael R.; Henderson, William G.; Valuck, Robert; Hosokawa, Patrick; Hammermeister, Karl

    2014-01-01

    Background Few comparative effectiveness studies of treatment strategies of the use of antihypertensive therapeutic classes in hypertension control have been assessed in a primary care environment. Objectives 1) To compare the effectiveness of common antihypertensive therapeutic classes initiated as monotherapy in control of hypertension; and 2) To compare the effectiveness of fixed-dose combinations (FDC), free-equivalent combinations (FEC) and monotherapy on hypertension control. Design Observational comparative effectiveness analyses of data electronically extracted from the electronic health records. Participants The study population consisted of 8,676 patients with an incident prescription for an antihypertensive agent out of 79,176 patients receiving antihypertensive therapy under care in 33 geographically diverse primary care clinics. Main Measures Reductions in systolic (SBP) and diastolic (DBP) blood pressure and rates of JNC7 goal attainment. Key Results There were small, clinically insignificant differences in BP reductions between the monotherapy classes. Higher rates of BP control were obtained when patients were initiated on an angiotensin-converting-enzyme inhibitor than a thiazide or thiazide-like diuretic (47.8% vs. 39.9%) or a beta-blocker versus a thiazide (45.9% vs. 39.9%). Patients initiated on FDCs had significantly larger reductions in BP than patients initiated on FECs (−17.3 vs. −12.0 mm Hg SBP; −10.1 vs. −6.0 mm Hg DBP) or monotherapy (−17.3 vs. −13.6 mm Hg SBP; −10.1 vs. −7.9 mm Hg DBP). Rates of JNC7 goal attainment also were better for FDCs than FECs (57.2% vs. 42.5%) and for FDCs versus monotherapy (57.2% vs. 44.9%). Conclusions Patients initiated on ACEIs and Beta-blockers had slightly higher rates of BP control. The use of FDCs as initial therapy is more effective in the control of hypertension than monotherapy or FECs. PMID:24004705

  2. Therapeutic Improvement of Scarring: Mechanisms of Scarless and Scar-Forming Healing and Approaches to the Discovery of New Treatments

    Directory of Open Access Journals (Sweden)

    Nick L. Occleston

    2010-01-01

    Full Text Available Scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in loss of function, restriction of tissue movement and adverse psychological effects. Whilst various studies have utilised a range of model systems that have increased our understanding of the pathways and processes underlying scar formation, they have typically not translated to the development of effective therapeutic approaches for scar management. Existing treatments are unreliable and unpredictable and there are no prescription drugs for the prevention or treatment of dermal scarring. As a consequence, scar improvement still remains an area of clear medical need. Here we describe the basic science of scar-free and scar-forming healing, the utility of pre-clinical model systems, their translation to humans, and our pioneering approach to the discovery and development of therapeutic approaches for the prophylactic improvement of scarring in man

  3. Evolution in the treatment of gastroenteropancreatic-neuroendocrine neoplasms, focus on systemic therapeutic options: a systematic review.

    Science.gov (United States)

    Pusceddu, Sara; De Braud, Filippo; Festinese, Fabrizio; Bregant, Cristina; Lorenzoni, Alice; Maccauro, Marco; Milione, Massimo; Concas, Laura; Formisano, Barbara; Leuzzi, Livia; Mazzaferro, Vincenzo; Buzzoni, Roberto

    2015-01-01

    Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors. The present review discusses current therapeutic strategies for the treatment of gastro-entero-pancreatic NEN. Several systemic options are currently available, including medical systemic chemotherapy, biological drugs, somatostatin analogs and peptide receptor radionuclide therapy. The carcinoid syndrome can be adequately controlled with somatostatin analogs; chemotherapy has shown positive outcomes in poor prognosis patients, and peptide receptor radionuclide therapy is a promising treatment based on the use of radioisotopes for advanced disease expressing somatostatin receptors. Targeted therapies, such as multikinase inhibitors and monoclonal antibodies are also recommended or under evaluation for the treatment of advanced NENs, but some critical issues in clinical practice remain unresolved. Depending upon the development of the disease, a multimodal approach is recommended. The treatment strategy for metastatic patients should be planned by a multidisciplinary team in order to define the optimal sequence of treatments.

  4. The psychometric development and initial validation of the DCI-A short form for adolescent therapeutic community treatment process.

    Science.gov (United States)

    Stucky, Brian D; Edelen, Maria Orlando; Vaughan, Christine A; Tucker, Joan S; Butler, Jennifer

    2014-04-01

    The 5-factor client-report Dimensions of Change in Therapeutic Communities Treatment Instrument-Adolescent (DCI-A) was developed to assess adolescent substance abuse treatment process in the therapeutic community (TC). The goal of this study was to use bifactor modeling to derive a unidimensional DCI-A short-form (DCI-A-SF) that would represent content from the original DCI-A factors. Data are from 442 adolescents receiving treatment at one of seven residential TC programs. Bifactor analyses suggested selection of seven DCI-A items to comprise the short form. Three items are from the treatment motivation factor, and one item was selected from each of the remaining four factors. Confirmatory factor analysis suggested that the 7-item DCI-A-SF is strongly unidimensional, and unidimensional IRT analysis of the items indicated good internal consistency. A structural equation model that demonstrates the mediating relationship of DCI-A-SF with other measures, including demographic and pre-treatment characteristics, and subsequent treatment completion, provides preliminary evidence of internal validity.

  5. OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE PLUS METHADONE FOR TREATMENT OF 50 CASES OF HEROIN ABSTINENCE SYNDROME

    Institute of Scientific and Technical Information of China (English)

    宋小鸽; 谷雨; 张浩

    2001-01-01

    At present, for treatment of narcotics abstinence, methadone replacement decremental remedy is most commenly applied. But if used for a longer time, it will lead to a new psychological dependence and tolerance. For avoiding this, we adopted acupuncture plus administration of methadone to treat 50 cases of heroin addition patients from July to September of 2 000 and achieved a good therapeutic effect. Here is the report.

  6. Recent advances in therapeutics and drug delivery for the treatment of inner ear diseases: a patent review (2011-2015).

    Science.gov (United States)

    Nguyen, Kim; Kempfle, Judith S; Jung, David H; McKenna, Charles E

    2017-02-01

    Inner ear disorders such as hearing loss, tinnitus, and Ménière's disease significantly impact the quality of life of affected individuals. Treatment of such disorders is an ongoing challenge. Current clinical approaches relieve symptoms but do not fully restore hearing, and the search for more effective therapeutic methods represents an area of urgent current interest. Areas covered: Thirty four patents and patent applications published from 2011 to 2015 were selected from the database of the U.S. Patent and Trademark Office (USPTO) and World Intellectual Property Organization (WIPO), covering new approaches for the treatment of inner ear disorders described in the patent literature: 1) identification of new therapeutic agents, 2) development of sustained release formulations, and 3) medical devices that facilitate delivery of such agents to the inner ear. Expert opinion: The search for effective treatments of inner ear disorders is ongoing. Increased understanding of the molecular mechanisms of hearing loss, Ménière's disease, and tinnitus is driving development of new therapeutic agents. However, delivery of these agents to the inner ear is a continuing challenge. At present, combination of a suitable drug with an appropriate mode of drug delivery is the key focus of innovative research to cure inner ear disorders.

  7. Comparative effectiveness of antihypertensive therapeutic classes and treatment strategies in the initiation of therapy in primary care patients: a Distributed Ambulatory Research in Therapeutics Network (DARTNet) study.

    Science.gov (United States)

    Bronsert, Michael R; Henderson, William G; Valuck, Robert; Hosokawa, Patrick; Hammermeister, Karl

    2013-01-01

    Few comparative effectiveness studies of treatment strategies using antihypertensive therapeutic classes in hypertension control have been assessed in a primary care environment. The objectives are to compare the effectiveness of common antihypertensive therapeutic classes initiated as monotherapy and of fixed-dose combinations (FDCs), free-equivalent combinations (FECs), and monotherapy on hypertension control. This article reports observational comparative effectiveness analyses of data electronically extracted from electronic health records. The study population consisted of 8,676 patients with an incident prescription for an antihypertensive agent of a total of 79,176 patients receiving antihypertensive therapy in 33 geographically diverse primary care clinics. The main measures were reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and rates of attaining goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). There were small, clinically insignificant differences in blood pressure reductions between the monotherapy classes. Higher rates of blood pressure control were obtained when patients were initiated on an angiotensin-converting enzyme inhibitor than a thiazide or thiazide-like diuretic (47.8% vs 39.9%) or a β-blocker versus a thiazide (45.9% vs 39.9%). Patients initiated on FDCs had significantly larger reductions in blood pressure than patients initiated on FECs (-17.3 vs -12.0 mm Hg SBP; -10.1 vs -6.0 mm Hg DBP) or monotherapy (-17.3 vs -13.6 mm Hg SBP; -10.1 vs -7.9 mm Hg DBP). Rates of attaining JNC7 goals also were better for FDCs than FECs (57.2% vs 42.5%) and for FDCs versus monotherapy (57.2% vs 44.9%). Patients initiated on angiotensin-converting enzyme inhibitors and β-blockers had slightly higher rates of blood pressure control. The use of FDCs as initial therapy is more effective in the control of hypertension than monotherapy

  8. A Therapeutic Wireless Capsule for Treatment of Gastrointestinal Haemorrhage by Balloon Tamponade Effect.

    Science.gov (United States)

    Leung, Billy H K; Poon, Carmen C Y; Zhang, Ruikai; Zheng, Y L; Chan, C K W; Chiu, Philip W Y; Lau, James Y W; Sung, Joseph J Y

    2016-07-13

    Wireless capsule endoscope (WCE) is a revolutionary approach to diagnose small bowel pathologies. Currently available WCEs are mostly passive devices with image capturing function only, while on-going efforts have been placed on robotizing WCEs or to enhance them with therapeutic functions. In this paper, the authors present a novel inflatable WCE for haemostasis in the gastrointestinal tracts by balloon tamponade effect.

  9. MMPI Patterns in Drug Abusers Before and After Treatment in Therapeutic Communities

    Science.gov (United States)

    Zuckerman, Marvin; And Others

    1975-01-01

    MMPI was given to 145 male and female drug abusers on admission to three therapeutic communities, and retests were done at the finish of the first phase of the program. Comparisons of stayers and quitters showed quitters higher on the F and psychotic scales. (Author)

  10. DermaVir: a plasmid DNA-based nanomedicine therapeutic vaccine for the treatment of HIV/AIDS.

    Science.gov (United States)

    Lori, Franco

    2011-10-01

    The HIV global pandemic continues to rage with over 33 million people living with the disease. Although multidrug therapy has improved the prognosis for those infected by the virus, it has not eradicated the infection. Immunological therapies, including therapeutic vaccines, are needed to supplement drug therapy in the search for a 'functional cure' for HIV. DermaVir (Genetic Immunity Kft, Budapest, Hungary and McLean, Virginia, USA), an experimental HIV/AIDS therapeutic vaccine, combines three key elements of rational therapeutic vaccine design: a single plasmid DNA (pDNA) immunogen expressing 15 HIV antigens, a synthetic pDNA nanomedicine formulation and a dendritic cell-targeting topical-vaccine administration. DermaVir's novel mechanism of action, natural transport by epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity, has been consistently demonstrated in mouse, rabbit, primate and human subjects. Safety, immunogenicity and preliminary efficacy of DermaVir have been clinically demonstrated in HIV-infected human subjects. The DermaVir technology platform for dendritic cell-based therapeutic vaccination might offer a new treatment paradigm for cancer and infectious diseases.

  11. INTRALESIONAL MEASLES, MUMPS AND RUBELLA (MMR VACCINE-AN EFFECTIVE THERAPEUTIC TOOL IN THE TREATMENT OF WART

    Directory of Open Access Journals (Sweden)

    Raju

    2015-11-01

    Full Text Available BACKGROUND: Warts are common cutaneous viral infection. Various therapeutic modalities have been using in treatment of wart, but none of them are standardised. Immunotherapy is new current approach in the treatment of wart. AIMS: To know the efficacy and safety profile of Measles Mumps Rubella (MMR Vaccine in the treatment of wart. METHODS: MMR vaccine was injected into a largest single wart intralesionally and subsequent injections given every 2 weeks apart for about 3 to 5 times. Every month followup of patients was done to know the clearance of wart. RESULTS: Complete remission of warts seen in 70.4% of patients, partial remission seen in 22.2% and no response was seen in 7.4% of patients. No serious adverse side effects were seen in the current study. CONCLUSION: MMR vaccine can be considered as a safe, effective, inexpensive intralesional immunotherapeutic modality in the treatment of wart.

  12. [Plasma exchange in treatment refractory septic shock : Presentation of a therapeutic add-on strategy].

    Science.gov (United States)

    David, S; Hoeper, M M; Kielstein, J T

    2017-02-01

    Sepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients' plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.

  13. Therapeutic modulation of miRNA for the treatment of proinflammatory lung diseases.

    LENUS (Irish Health Repository)

    Hassan, Tidi

    2012-03-01

    miRNAs are short, nonprotein coding RNAs that regulate target gene expression principally by causing translational repression and\\/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signaling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry, such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art miRNA-targeted therapeutics.

  14. Ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics.

    Science.gov (United States)

    Corben, Adriana D; Uddin, Mohammad M; Crawford, Brooke; Farooq, Mohammad; Modi, Shanu; Gerecitano, John; Chiosis, Gabriela; Alpaugh, Mary L

    2014-10-02

    The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

  15. Recurrent massive bleeding due to dissecting intramural hematoma of the esophagus: Treatment with therapeutic angiography

    Institute of Scientific and Technical Information of China (English)

    Jaejun Shim; Jae Young Jang; Young Hwangbo; Seok Ho Dong; Joo Hyeong Oh; Hyo Jong Kim; Byung-Ho Kim; Young Woon Chang; Rin Chang

    2009-01-01

    Spontaneous or traumatic intramural bleeding of the esophagus, which is often associated with overlying mucosal dissection, constitutes a rare spectrum of esophageal injury called dissecting intramural hematoma of the esophagus (DIHE). Chest pain, swallowing difficulty, and minor hematemesis are common, which resolve spontaneously in most cases. This case report describes a patient with spontaneous DIHE with recurrent massive bleeding which required critical management and highlights a potential role for therapeutic angiography as an alternative to surgery.

  16. HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST)

    OpenAIRE

    Gonzalo Lopez; Bill, Kate Lynn J.; Hemant Kumar Bid; Danielle Braggio; Dylan Constantino; Bethany Prudner; Abeba Zewdu; Kara Batte; Dina Lev; Pollock, Raphael E.

    2015-01-01

    Introduction HDAC isoform-specific inhibitors may improve the therapeutic window while limiting toxicities. Developing inhibitors against class I isoforms poses difficulties as they share high homology among their catalytic sites; however, HDAC8 is structurally unique compared to other class I isoforms. HDAC8 inhibitors are novel compounds and have affinity for class I HDAC isoforms demonstrating anti-cancer effects; little is known about their activity in malignant peripheral nerve sheath tu...

  17. THERAPEUTIC PLAY AS TECHNIQUE SUPPORTING TO PHYSIOTHERAPEUTIC TREATMENT IN CHILDREN WITH RESPIRATORY DISORDERS

    OpenAIRE

    Schenkel,Isabel de Castro; Garcia, Júlia Macruz; Berretta, Marina da Silva Kleinubing; da Silva, Maria Eduarda Merlin; Schivinski, Camila Isabel Santos

    2013-01-01

    Abstract: This integrative review aims to provide publications concerning about the use of therapeutic play during sessions of physical therapy in children with respiratory disorders. This kind of intervention such funds placed in care as a strategy to motivate and teach children. The revision was carried out in the databases PubMed, Medline, SciELO, Lilacs, Science Direct, using the descriptors: respiratory therapy, pediatrics and play and playthings. From a total of 73 publications, 36 work...

  18. Therapeutics Insight with Inclusive Immunopharmacology Explication of Human Rotavirus A for the Treatment of Diarrhea

    Science.gov (United States)

    Hossain, Mohammad Uzzal; Hashem, Abu; Keya, Chaman Ara; Salimullah, Md.

    2016-01-01

    Rotavirus is the most common cause of severe infant and childhood diarrhea worldwide, and the morbidity and mortality rate is going to be outnumbered in developing countries like Bangladesh. To mitigate this substantial burden of disease, new therapeutics such as vaccine and drug are swiftly required against rotavirus. The present therapeutics insight study was performed with comprehensive immunoinformatics and pharmacoinformatics approach. T and B-cell epitopes were assessed in the conserved region of outer capsid protein VP4 among the highly reviewed strains from different countries including Bangladesh. The results suggest that epitope SU1 (TLKNLNDNY) could be an ideal candidate among the predicted five epitopes for both T and B-cell epitopes for the development of universal vaccine against rotavirus. This research also suggests five novel drug compounds from medicinal plant Rhizophora mucronata Lamk. for better therapeutics strategies against rotavirus diarrhea based on 3D structure building, pharmacophore, ADMET, and QSAR properties. The exact mode of action between drug compounds and target protein VP4 were revealed by molecular docking analysis. Drug likeness and oral bioavailability further confirmed the effectiveness of the proposed drugs against rotavirus diarrhea. This study might be implemented for experimental validation to facilitate the novel vaccine and drug design. PMID:27445802

  19. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease.

  20. Measuring therapeutic alliance with children in residential treatment and therapeutic day care: a validation study of the Children’s Alliance Questionnaire

    NARCIS (Netherlands)

    J. Roest; P. van der Helm; E. Strijbosch; M. van Brandenburg; G.J. Stams

    2014-01-01

    Purpose: This study examined the construct validity and reliability of a therapeutic alliance measure (Children’s Alliance Questionnaire [CAQ]) for children with psychosocial and/or behavioral problems, receiving therapeutic residential care or day care in the Netherlands. Methods: Confirmatory fact

  1. OBSERVATION ON THE THERAPEUTIC EFFECT OF TREATMENT OF 150CASES OF INSOMNIA BY PUNCTURING BODY ACUPOINTS AND OTOPOINTS

    Institute of Scientific and Technical Information of China (English)

    李宗莲

    2000-01-01

    In the present paper,the therapeutic effect of needling Baihui(GV20)and Sishen-chong(EX-HN1)combined with otopoint Xin(MA-IC),Shenmen,Naodian and pizhixia(MA-AT1)for treatment of insomnia was observed in 150patients.Results showed that the cure rate,effective rate and ineffective rate were84%,13.33%and2.67%respectively.Comparison between Western medicine group and acupuncture group showed a significant difference in the therapeutic effect(P<0.01).It displays that acupuncture can correct the imbalance between excitement and suppression of the cerebral cortex and had effects of tranquilizing and allaying excitement.

  2. A Comparative Study between Oxcarbazepine and Gabapentin Regarding Therapeutic Efficiency and Tolerability in the Treatment of Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Fakir Mohan Debta

    2010-01-01

    Recently two newer anticonvulsant oxcarbazepine (OXC a ketoderivative of carbamazepine and gabapentin (GBP has been trailed in trigeminal neuralgia in different open clinical trial as monotherapy with encouraging results. These drugs have convenient dosage and surprisingly fewer side effects. These facts that trigeminal neuralgia responds to newer anticonvulsant (oxcarbazepine, gabapentin in a better perspective, enabled me to conduct the present clinical trial on 54 patients (both in newly diagnosed TN patient and refractive patient of trigeminal neuralgia who were made two randomized group for separate monotherapy study for a period of six months. The therapeutic effect of OXC and gabapentin (GBP in relation to reduction in number of attacks of pain and severity of pain were evaluated. All the scoring data showed OXC is more therapeutic efficacious cost-effective and well-tolerated profile than gabapentin and an emerging as a drug for treatment of TN in both new and refractive patients.

  3. Comparative study of the therapeutic effects of corticosteroid injection accompanied by casting and heel pad in treatment of heel pain

    Directory of Open Access Journals (Sweden)

    Mehdi Motififard

    2008-08-01

    Full Text Available

    • BACKGROUND: Heel pain is a common condition in adults that may cause significant discomfort and disability. This study was conducted to evaluate the therapeutic effects of corticosteroid injection accompanied by casting, compared with heel pad utilization in treatment of heel pain.
    • METHODS: In this randomized clinical trial study, among patients referred to orthopedic clinics in Isfahan, Iran, from December 2004 to December 2006, 90 patients with heel pain were enrolled. They were randomly assigned into two groups. Heel pad was the only therapeutic method utilized in group A for six months. Corticosteroid injection accompanied by casting was performed for patients in group B. The evaluated information was compared before and after treatment.
    •  RESULTS: Among patients in group A, after 6 months of heel pad utilization, heel pain was completely improved in 3 patients (6.7%, relatively decreased in 22 patients (48.9% and didn't change in 20 patients (44.4%. However, among patients in group B, heel pain was completely improved in 11 patients (24.5%, decreased in 29 patients (64.4% and didn't change in 5 patients (11.1% after the treatment completed.
    • CONCLUSIONS: It seemed that corticosteroid injection in companion with casting was a more effective therapeutic method in heel pain treatment than heel pad utilization.
    • KEYWORDS: Corticosteroid injection, casting, heel pad, heel pain.

  4. Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Holly Fitch

    2013-03-01

    Full Text Available Hypoxia Ischemia (HI refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen. Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p. injection of caffeine (10 mg/kg, or vehicle (sterile saline immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM from P90 to P95. Results show that HI injured animals (with no caffeine treatment displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

  5. Differential effectiveness of residential versus outpatient aftercare for parolees from prison-based therapeutic community treatment programs

    Directory of Open Access Journals (Sweden)

    Messina Nena P

    2007-05-01

    Full Text Available Abstract Background Research has indicated that more intense treatment is associated with better outcomes among clients who are appropriately matched to treatment intensity level based on the severity of their drug/alcohol problem. This study examined the differential effectiveness of community-based residential and outpatient treatment attended by male and female drug-involved parolees from prison-based therapeutic community substance abuse treatment programs based on the severity of their drug/alcohol problem. Methods Subjects were 4,165 male and female parolees who received prison-based therapeutic community substance abuse treatment and who subsequently participated in only outpatient or only residential treatment following release from prison. The dependent variable of interest was return to prison within 12 months. The primary independent variables of interest were alcohol/drug problem severity (low, high and type of aftercare (residential, outpatient. Chi-square analyses were conducted to examine the differences in 12-month RTP rates between and within the two groups of parolees (residential and outpatient parolees based on alcohol/drug problem severity (low severity, high severity. Logistic regression analyses were performed to determine if aftercare modality (outpatient only vs. residential only was a significant predictor of 12-month RTP rates for subjects who were classified as low severity versus those who were classified as high severity. Results Subjects benefited equally from outpatient and residential aftercare, regardless of the severity of their drug/alcohol problem. Conclusion As states and the federal prison system further expand prison-based treatment services, the demand and supply of aftercare treatment services will also increase. As this occurs, systems and policies governing the transitioning of individuals from prison- to community-based treatment should include a systematic and validated assessment of post

  6. An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments.

    Directory of Open Access Journals (Sweden)

    Boyuan Yan

    Full Text Available Many types of epileptic seizures are characterized by generalized spike-and-wave discharges. In the past, notable effort has been devoted to understanding seizure dynamics and various hypotheses have been proposed to explain the underlying mechanisms. In this paper, by taking an integrative view of the underlying mechanisms, we demonstrate that epileptic seizures can be generated by many different combinations of synaptic strengths and intrinsic membrane properties. This integrative view has important medical implications: the specific state of a patient characterized by a set of biophysical characteristics ultimately determines the optimal therapeutic treatment. Through the same view, we further demonstrate the potentiation effect of rational polypharmacy in the treatment of epilepsy and provide a new angle to resolve the debate on polypharmacy. Our results underscore the need for personalized medicine and demonstrate that computer modeling and simulation may play an important role in assisting the clinicians in selecting the optimal treatment on an individual basis.

  7. Targeting Specific HATs for Neurodegenerative Disease Treatment: Translating Basic Biology to Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    Sheila K. Pirooznia

    2013-03-01

    Full Text Available Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HATs activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and

  8. A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment

    Science.gov (United States)

    2015-10-01

    overexpressed pharmacologically, thus PKD1 inducer could be use in clinic for therapeutic purpose. Bryostatin -1 use in clinic has some limitations because...contraceptive and for the management of hormone-related clinical disorders. Med Res Rev, 2001. 21(4): p. 302-47. 11. Jaggi, M., et al., Bryostatin 1 modulates...Marshall, J.L., et al., Phase I study of prolonged infusion Bryostatin -1 in patients with advanced malignancies. Cancer Biol Ther, 2002. 1(4): p. 409-16

  9. Evaluation of the Chinese Medicinal Herb, Graptopetalum paraguayense, as a Therapeutic Treatment for Liver Damage in Rat Models

    Directory of Open Access Journals (Sweden)

    Li-Jen Su

    2012-01-01

    Full Text Available The incidence of cirrhosis is rising due to the widespread occurrence of chronic hepatitis, as well as the evident lack of an established therapy for hepatic fibrosis. In the search for hepatoprotective therapeutic agents, Graptopetalum paraguayense (GP showed greater cytotoxicity toward hepatic stellate cells than other tested herbal medicines. Histopathological and biochemical analyses suggest that GP treatment significantly prevented DMN-induced hepatic inflammation and fibrosis in rats. Microarray profiling indicated that expression of most of metabolism- and cell growth and/or maintenance-related genes recovered to near normal levels following GP treatment as classified by gene ontology and LSM analysis, was observed. ANOVA showed that expression of 64% of 256 liver damage-related genes recovered significantly after GP treatment. By examining rat liver samples with Q-RT-PCR, five liver damage-related genes were identified. Among them, Egr1 and Nrg1 may serve as necroinflammatory markers, and Btg2 may serve as a fibrosis marker. Oldr1 and Hmgcs1 were up- and down-regulated markers, respectively. A publicly accessible website has been established to provide access to these data Identification of 44 necroinflammation-related and 62 fibrosis-related genes provides useful insight into the molecular mechanisms underlying liver damage and provides potential targets for the rational development of therapeutic drugs such as GP.

  10. Self-Assembled ROS-Sensitive Polymer-Peptide Therapeutics Incorporating Built-in Reporters for Evaluation of Treatment Efficacy.

    Science.gov (United States)

    Qiao, Zeng-Ying; Zhao, Wen-Jing; Cong, Yong; Zhang, Di; Hu, Zhiyuan; Duan, Zhong-Yu; Wang, Hao

    2016-05-09

    One of the major challenges in current cancer therapy is to maximize therapeutic effect and evaluate tumor progression under the scheduled treatment protocol. To address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated amphiphilic poly(β-thioester)s copolymers (H-P-K) composed of reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene glycol (PEG) side chains. H-P-K could self-assemble into micelle-like nanoparticles by hydrophobic interaction with copolymer backbones as cores and PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably improved cellular internalization and accumulation of therapeutic KLAK in cells. Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly enhanced up to ∼400 times, suggesting the effectiveness of the nanoscaled polymer-peptide conjugation as biopharmaceuticals. The higher antitumor activity of nanoparticles was attributed to the efficient disruption of mitochondrial membranes and subsequent excessive ROS production in cells. To realize the ROS monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built-in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around mitochondria stimulated the swelling of nanoparticles and subsequent release of SQ, which formed H-aggregates and significantly increased the photoacoustic (PA) signal. We believed that this self-assembled polymer-peptide nanotherapeutics incorporating built-in reporters has great potential for high antitumor performance and in situ treatment evaluation.

  11. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  12. Dopamine D3 receptor antagonists as potential therapeutics for the treatment of neurological diseases

    Directory of Open Access Journals (Sweden)

    Samuele Maramai

    2016-10-01

    Full Text Available D3 receptors represent a major focus of current drug design and development of therapeutics for dopamine-related pathological states. Their close homology with the D2 receptor subtype makes the development of D3 selective antagonists a challenging task. In this review, we explore the relevance and therapeutic utility of D3 antagonists or partial agonists endowed with multireceptor affinity profile in the field of central nervous system disorders such as schizophrenia and drug abuse. In fact, the peculiar distribution and low brain abundance of D3 receptors make them a valuable target for the development of drugs devoid of motor side effects classically elicited by D2 antagonists. Recent research efforts were devoted to the conception of chemical templates possibly endowed with a multi-target profile, especially with regards to other G-protein-coupled receptors (GPCRs.A comprehensive overview of the recent literature in the field is herein provided. In particular, the evolution of the chemical templates has been tracked, according to the growing advancements in both the structural information and the refinement of the key pharmacophoric elements.The receptor/multireceptor affinity and functional profiles for the examined compounds has been covered, together with their most significant pharmacological applications.

  13. Neuroinflammation: A Therapeutic Target of Cotinine for the Treatment of Psychiatric Disorders?

    Science.gov (United States)

    Echeverria, Valentina; Grizzell, J Alex; Barreto, George E

    2016-01-01

    Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug development. Cotinine is an alkaloid present in tobacco leaves and the main metabolite of nicotine. Cotinine is safe, non-addictive and has pharmacokinetic properties adequate for therapeutic use. Research has shown that cotinine has antipsychotic, anxiolytic, and antidepressant properties and modulates the serotonergic, cholinergic and dopaminergic systems. Consistent with the modulation of these neurotransmitter systems, cotinine behaves as a positive allosteric modulator of the nicotinic acetylcholine receptors (nAChRs) and has anti-inflammatory effects. The decrease in neuroinflammation induced by the stimulation of the cholinergic system seems to be a key element explaining the beneficial effects of cotinine in a diverse range of neurological and psychiatric conditions. This review discusses new evidence of the role of neuroinflammation as a key aspect in bipolar disorder, PTSD and major depression, as well as the potential use of cotinine to reduce neuroinflammation in those conditions.

  14. Therapeutic Potential and Challenges of Natural Killer Cells in Treatment of Solid Tumors

    Science.gov (United States)

    Gras Navarro, Andrea; Björklund, Andreas T.; Chekenya, Martha

    2015-01-01

    Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing, requiring one-to-one target engagement and site-directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells, and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME) and augment adaptive immune responses by promoting differentiation, activation, and/or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes, and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach. PMID:25972872

  15. Novel therapeutic agents for HbF induction: a new era for treatment of β thalassemia?

    Directory of Open Access Journals (Sweden)

    S.P. Perrine

    2011-12-01

    Full Text Available Fetal globin is endogenous, normally integrated in hematopoietic stem cells in all humans, and available for reactivation. Inducing expression of fetal globin (g-globin gene expression to 60-70% of a globin synthesis produces β-thalassemia trait globin synthetic ratios, and has been shown to reduce anemia to mild levels which do not require regular blood transfusion. Several classes of therapeutics have induced g-globin expression in β thalassemia patients, raised total hemoglobin levels, and even eliminated transfusion requirements in formerly transfusion-dependent patients, demonstrating proof-of-concept of the approach. However, prior generations of therapeutics were not readily feasible for widespread use. Currently, several recently discovered oral therapeutic candidates are more potent and/ or patientfriendly, requiring low oral doses, have distinct molecular mechanisms of action, and can be used in combination regimens. Tailoring therapeutic regimens to patient subsets stratified for solely β+ or a β0 globin mutation, and for quantitative trait loci (QTL which modulate HbF and clinical severity, can guide more effective and informative clinical trials. These advancements provide methods for a rational approach to applying fetal globin gene induction in therapeutic regimens suitable for use in diverse thalassemia patient populations world-wide. 胎儿珠蛋白是内生的,通常结合在所有人类的造血干细胞中,并可进行再激活。 包括胎儿珠蛋白的表达(g-珠蛋白),60%-70% 珠蛋白合成基因表达产生 β地中海贫血特征珠蛋白合成比率,并且已经显示将贫血降低至轻度水平,这不需要常规输血 几类疗法诱导β地中海贫血患者中的g-珠蛋白的表达,升高了血红蛋白的总体水平,甚至让以前依靠输血的患者不再需要输血,这演示了此方法的概念验证。 不过,先前几代疗法未能进行广泛使用。 目前,最近发

  16. Individualized treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring

    Directory of Open Access Journals (Sweden)

    Mathieu S Bolhuis

    2016-01-01

    Conclusion: TDM is highly valuable to individualize and optimize treatment of complex MDR-TB patients. TDM is routinely applied in Tuberculosis Center Beatrixoord, and high success rates for treatment of MDR-TB patients have been achieved. DBS and LSS make implementation of TDM feasible, even in low- and middle-income countries.

  17. Individualized treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring

    NARCIS (Netherlands)

    Bolhuis, Mathieu S; Akkerman, Onno W; Sturkenboom, Marieke G G; de Lange, Wiel C M; van der Werf, Tjip S; Alffenaar, Jan-Willem C

    2016-01-01

    OBJECTIVE/BACKGROUND: Globally, approximately 50% of patients with multidrug-resistant tuberculosis (MDR-TB) experience treatment failure. MDR-TB treatment is hindered by adverse events, toxicity of the second-line anti-TB drugs, logistics and costs, especially in low-income countries, and problems

  18. The treatment of venous leg ulcers - A new therapeutic use of Iloprost

    NARCIS (Netherlands)

    Ferrara, Filippo; Meli, Francesco; Raimondi, Francesco; Amato, Corrado; Bonura, Francesca; Mule, Giuseppe; Novo, Giuseppina; Salvatore, Novo S.

    2007-01-01

    Background: We conducted a study using an intravenous (i.v.) infusion of iloprost in the treatment of venous ulcers to verify whether the association of i.v. iloprost + local therapy + elastic compression has a favorable effect when compared with traditional treatment with local therapy and elastic

  19. Assessing the Therapeutic Environment in Hybrid Models of Treatment: Prisoner Perceptions of Staff

    Science.gov (United States)

    Kubiak, Sheryl Pimlott

    2009-01-01

    Hybrid treatment models within prisons are staffed by both criminal justice and treatment professionals. Because these models may be indicative of future trends, examining the perceptions of prisoners/participants may provide important information. This study examines the perceptions of male and female inmates in three prisons, comparing those in…

  20. Peptide Regulation of Cofilin Activity in the CNS: A Novel Therapeutic Approach for Treatment of Multiple Neurological Disorders.

    Science.gov (United States)

    Shaw, Alisa E; Bamburg, James R

    2017-02-19

    Cofilin is a ubiquitous protein which cooperates with many other actin-binding proteins in regulating actin dynamics. Cofilin has essential functions in nervous system development including neuritogenesis, neurite elongation, growth cone pathfinding, dendritic spine formation, and the regulation of neurotransmission and spine function, components of synaptic plasticity essential for learning and memory. Cofilin's phosphoregulation is a downstream target of many transmembrane signaling processes, and its misregulation in neurons has been linked in rodent models to many different neurodegenerative and neurological disorders including Alzheimer disease (AD), aggression due to neonatal isolation, autism, manic/bipolar disorder, and sleep deprivation. Cognitive and behavioral deficits of these rodent models have been largely abrogated by modulation of cofilin activity using viral-mediated, genetic, and/or small molecule or peptide therapeutic approaches. Neuropathic pain in rats from sciatic nerve compression has also been reduced by modulating the cofilin pathway within neurons of the dorsal root ganglia. Neuroinflammation, which occurs following cerebral ischemia/reperfusion, but which also accompanies many other neurodegenerative syndromes, is markedly reduced by peptides targeting specific chemokine receptors, which also modulate cofilin activity. Thus, peptide therapeutics offer potential for cost-effective treatment of a wide variety of neurological disorders. Here we discuss some recent results from rodent models using therapeutic peptides with a surprising ability to cross the rodent blood brain barrier and alter cofilin activity in brain. We also offer suggestions as to how neuronal-specific cofilin regulation might be achieved.

  1. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin

    Science.gov (United States)

    Seufert, Jochen

    2015-01-01

    Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM) are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These “concomitant effects” are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand the treatment options for patients at every stage of T2DM. The efficacy and tolerability of canagliflozin have been tested in an extensive clinical trial program

  2. SGLT2 inhibitors - an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin.

    Science.gov (United States)

    Seufert, Jochen

    2015-01-01

    Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM) are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These "concomitant effects" are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand the treatment options for patients at every stage of T2DM. The efficacy and tolerability of canagliflozin have been tested in an extensive clinical trial program

  3. Therapeutic efficiency of succimer used with calcium and ascorbic acid in the treatment of mild lead-poisoning.

    Science.gov (United States)

    Jin, Yaping; Yu, Fei; Liao, Yingjun; Liu, Shaoxia; Liu, Meimei; Xu, Jianhong; Yang, Jun

    2011-01-01

    The aim of this study was to explore therapeutic efficiency of succimer used with calcium and ascorbic acid in the treatment of mildly lead-poisoned mice and preschool children. Mice were exposed to lead by drinking water, and then treated with saline solution, 50mg/kg body weight (b.w.) succimer, 100mg/kg b.w. succimer, or 50mg/kg b.w. succimer plus calcium and ascorbic acid by gavage. Seventy-two children aged 48-72 months were randomly assigned into combined treatment or nutritional intervention group. Lead levels in blood and bone were analyzed by atomic absorption spectrophotometry. Activities of aminolevulinic acid dehydratase (ALAD) in blood were determined by colorimetric method. Results of animal experiment showed that succimer used alone could reduce lead levels in blood and bone and reverse activities of ALAD in blood, however, a better therapeutic efficiency in mobilizing bone lead could be achieved by succimer used with calcium and ascorbic acid. Findings from the clinical study showed that reduction of blood lead levels (BLLs) between the end and initiation of therapy in the combined treatment group was significantly greater than that in the nutritional intervention group. Percentage of children with BLLs less than 10μg/dL at the end of therapy and the eighth week after therapy in the combined treatment group was significantly higher than that in the nutritional intervention group. In conclusion, combined use of succimer with calcium and ascorbic acid seemed to be a choice in the treatment of mildly lead poisoned children.

  4. Observation on Therapeutic Effect of Clapping Acupoint for Treatment of Hyperosteoyeny of Lumbar Vertebra

    Institute of Scientific and Technical Information of China (English)

    CAI Qiu-sheng; WANG Hua; WU Xue-fei

    2003-01-01

    Objective To observe the effect of clapping acupoint on hyperosteogeny of lumbar vertebra. Methods Ninety-eight cases were randomly divided into 65 cases treated by clapping Ashi point in treatment group and 33cases treated by simple acupuncture in control group.Results Among 65 cases in treatment group, 52 cases were cured and 13 cases were not cured; of 33 cases in control group, 19 cases were cured and 14 cases were not cured, and there had significant difference in cure rate between the two groups, x2 =5.51, P <0.05. Conclusion Treatment of hyperosteogeny by clapping acupoint was better than simple acupuncture therapy.

  5. [Therapeutic action of oral mesoglycan in the pharmacologic treatment of the varicose syndrome and its complications].

    Science.gov (United States)

    Petruzzellis, V; Velon, A

    1985-03-24

    The comparative therapeutic efficacy of mesoglycan and a capillary protective drug derived from rutin was evaluated in a clinical study conducted on a group of patients with varicose syndrome and/or its complications. The clinical assessment of the results obtained was followed by a series of investigations aimed at identifying the action mechanism of the drugs under study. In the experimental model adopted, mesoglycan was found to be well tolerated and effective both in absolute terms and in comparison with the drug used for comparison. Apart from the clinical efficacy of mesoglycan, it was also shown to increase transcutaneous O2 perfusion and blood flow as evidenced by filtrability. On the basis of these results it is suggested that the clinical action and tolerability of mesoglycan make it a valuable aid in the arduous task of treating varicose syndrome and its complications.

  6. Treatment of prostate cancer: therapeutic potential of targeted immunotherapy with APC8015

    Directory of Open Access Journals (Sweden)

    Robert A Bok

    2008-03-01

    Full Text Available Robert A BokDepartment of Radiology, University of California at San Francisco, San Francisco, CA, USAAbstract: The body’s immune system has some capacity to recognize and attack cancerous growths, including prostate cancer. However, various intrinsic characteristics of tumor cells usually limit that capacity. Therapeutically administered immunologic stimuli, such as APC8015, an individualized, ex vivo stimulation of a patient’s own antigen presenting cells (APC, are capable of boosting the anti-tumor response. Late phase clinical trials of APC8015 (now also called Sipuleucel-T show evidence of slowing disease progression and increasing survival in advanced prostate cancer. Such immunotherapeutic approaches hold real promise to provide additional useful and welcome weapons against this common malignancy.Keywords: prostate cancer, antigen presenting cells, immunologics

  7. HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST.

    Directory of Open Access Journals (Sweden)

    Gonzalo Lopez

    Full Text Available HDAC isoform-specific inhibitors may improve the therapeutic window while limiting toxicities. Developing inhibitors against class I isoforms poses difficulties as they share high homology among their catalytic sites; however, HDAC8 is structurally unique compared to other class I isoforms. HDAC8 inhibitors are novel compounds and have affinity for class I HDAC isoforms demonstrating anti-cancer effects; little is known about their activity in malignant peripheral nerve sheath tumors (MPNST. Recently, we demonstrated anti-MPNST efficacy of HDAC8i in human and murine-derived MPNST pre-clinical models; we now seek to consider the potential therapeutic inhibition of HDAC8 in MPNST.Four Human MPNST cell lines, a murine-derived MPNST cell line, and two HDAC8 inhibitors (PCI-34051, PCI-48012; Pharmacyclics, Inc. Sunnyvale, CA were studied. Proliferation was determined using MTS and clonogenic assays. Effects on cell cycle were determined via PI FACS analysis; effects on apoptosis were determined using Annexin V-PI FACS analysis and cleaved caspase 3 expression. In vivo growth effects of HDAC8i were evaluated using MPNST xenograft models. 2D gel electrophoresis and mass spectrometry were used to identify potential HDAC8 deacetylation substrates.HDAC8i induced cell growth inhibition and marked S-phase cell cycle arrest in human and murine-derived MPNST cells. Relative to control, HDAC8i induced apoptosis in both human and murine-derived MPNST cells. HDAC8i exhibited significant effects on MPNST xenograft growth (p=0.001 and tumor weight (p=0.02. Four potential HDAC8 substrate targets were identified using a proteomic approach: PARK7, HMGB1, PGAM1, PRDX6.MPNST is an aggressive sarcoma that is notoriously therapy-resistant, hence the urgent need for improved anti-MPNST therapies. HDAC8 inhibition may be useful for MPNST by improving efficacy while limiting toxicities as compared to pan-HDACis.

  8. THERAPEUTIC CAPABILITIES OF ETHANERCEPT IN TREATMENT OF SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2011-01-01

    Full Text Available The article presents a clinical case of severe systemic juvenile rheumatoid arthritis, refractory to traditional immunosuppressive treatment and with insufficient efficacy of chimeric homogenous anti-TNF-a antibodies. The patient received 2 courses of anti-Blymphocyte’s- CD20-antibodies that helped to arrest all systemic manifestations of the disease. Articular syndrome was arrested only with the help of soluble receptors to TNF a — ethanercept, given in following dose — 0.4 mg per kg of body mass. The patient has been on treatment with ethanercept for 24 weeks. Joint tenderness and exudation were diminished already after the first 4 weeks of treatment, also there was a dramatic increase in joint motion range. After 6 months of therapy we have managed to improve the patients and his family quality of life.Key words: children, juvenile rheumatoid arthritis, ethanercept, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 141–149

  9. Treatment Outcomes of Corticosteroid Injection and Extracorporeal Shock Wave Therapy as Two Primary Therapeutic Methods for Acute Plantar Fasciitis: A Prospective Randomized Clinical Trial.

    Science.gov (United States)

    Mardani-Kivi, Mohsen; Karimi Mobarakeh, Mahmoud; Hassanzadeh, Zabihallah; Mirbolook, Ahmadreza; Asadi, Kamran; Ettehad, Hossein; Hashemi-Motlagh, Keyvan; Saheb-Ekhtiari, Khashayar; Fallah-Alipour, Keyvan

    2015-01-01

    The outcome of corticosteroid injection (CSI) and extracorporeal shock wave therapy (ESWT) as primary treatment of acute plantar fasciitis has been debated. The purpose of the present study was to evaluate and compare the therapeutic effects of CSI and ESWT in patients with acute ( .05). Both ESWT and CSI can be used as the primary and/or initial treatment option for treating patients with acute plantar fasciitis; however, the CSI technique had better therapeutic outcomes.

  10. Treatment of Insomnia, Insomnia Symptoms, and Obstructive Sleep Apnea During and After Menopause: Therapeutic Approaches

    OpenAIRE

    Tal, Joshua Z.; Suh, Sooyeon A.; Dowdle, Claire L.; Nowakowski, Sara

    2015-01-01

    Understanding sleep complaints among menopausal women is an emerging area of clinical and research interest. Several recent reviews have focused on mechanisms of menopausal insomnia and symptoms. In this review, we present a discussion on the most relevant and recent publications on the treatment of sleep disorders for menopausal women, with a focus on menopause-related insomnia, insomnia symptoms, and obstructive sleep apnea. We discuss both nonpharmacological and pharmacological treatments,...

  11. Effectiveness of a therapeutic community treatment in Spain: a long-term follow-up study.

    Science.gov (United States)

    Fernández-Hermida, José-Ramón; Secades-Villa, Roberto; Fernández-Ludeña, José-Javier; Marina-González, Pedro-Antonio

    2002-01-01

    In this paper, the effectiveness of the treatment program developed by Proyecto Hombre ('Project Mankind') in Asturias, Spain, is evaluated. In a long-term follow-up (range from 73 days to 8 years) with a sample of 249 subjects, the results obtained by subjects completing the treatment (194) were compared with pre-treatment results and with those of the group that dropped out (55). The measurements used were relapses in illegal drugs, alcohol, changes in family situation, educational level, employment, criminal involvement and state of health. External validation of self-report measures given in the questionnaire was carried out. Findings support the effectiveness of the treatment in all measures and the validity of self-report items. Relapse rate in 'treatment-completed' group was 10.3%, whilst in the non-completers group it reached 63.6% (significant difference, p < 0.001). Relapses of non-completers were more severe, occurred sooner after leaving the program (they stayed abstinent for shorter periods) and lasted longer than those of subjects completing the treatment.

  12. Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus.

    Science.gov (United States)

    Holz, George G; Chepurny, Oleg G

    2003-11-01

    Glucagon-like peptide-1-(7-36)-amide (GLP-1) is a potent blood glucose-lowering hormone now under investigation for use as a therapeutic agent in the treatment of type 2 (adult onset) diabetes mellitus. GLP-1 binds with high affinity to G protein-coupled receptors (GPCRs) located on pancreatic beta-cells, and it exerts insulinotropic actions that include the stimulation of insulin gene transcription, insulin biosynthesis, and insulin secretion. The beneficial therapeutic action of GLP-1 also includes its ability to act as a growth factor, stimulating formation of new pancreatic islets (neogenesis) while slowing beta-cell death (apoptosis). GLP-1 belongs to a large family of structurally-related hormones and neuropeptides that include glucagon, secretin, GIP, PACAP, and VIP. Biosynthesis of GLP-1 occurs in the enteroendocrine L-cells of the distal intestine, and the release of GLP-1 into the systemic circulation accompanies ingestion of a meal. Although GLP-1 is inactivated rapidly by dipeptidyl peptidase IV (DDP-IV), synthetic analogs of GLP-1 exist, and efforts have been directed at engineering these peptides so that they are resistant to enzymatic hydrolysis. Additional modifications of GLP-1 incorporate fatty acylation and drug affinity complex (DAC) technology to improve serum albumin binding, thereby slowing renal clearance of the peptides. NN2211, LY315902, LY307161, and CJC-1131 are GLP-1 synthetic analogs that reproduce many of the biological actions of GLP-1, but with a prolonged duration of action. AC2993 (Exendin-4) is a naturally occurring peptide isolated from the lizard Heloderma, and it acts as a high affinity agonist at the GLP-1 receptor. This review summarizes structural features and signal transduction properties of GLP-1 and its cognate beta-cell GPCR. The usefulness of synthetic GLP-1 analogs as blood glucose-lowering agents is discussed, and the applicability of GLP-1 as a therapeutic agent for treatment of type 2 diabetes is highlighted.

  13. Sipuleucel-T: a therapeutic cancer vaccine for the treatment of castration- or hormone-refractory prostate cancer.

    Science.gov (United States)

    Bulloch, Marilyn N; Elayan, Mohammed M; Renfroe, Holly R

    2011-11-01

    Sipuleucel-T is a therapeutic cancer vaccine approved for the treatment of castration- or hormone-refractory prostate cancer. Through a novel process, it activates the body's own antigen-presenting cells to induce an immune response to prostatic acid phosphatase, a protein found on prostate cancer cells. A treatment course consists of three total infusions spread 2 weeks apart. Throughout all phases of clinical trials, sipuleucel-T has been shown to be safe and well tolerated. Sipuleucel-T has demonstrated an ability to increase overall survival by approximately 4 months when compared with placebo. However, sipuleucel-T has not shown any improvement in affecting patients' time to disease progression.

  14. Is TNF-a-targeted short hairpin RNA (shRNA) a novel potential therapeutic tool in psoriasis treatment?

    DEFF Research Database (Denmark)

    Stenderup, Karin; Jakobsen, Maria; Rosada, Cecilia

    2008-01-01

      TNF-α is a well known target in psoriasis treatment and biological treatments targeting TNF-a are already clinically used against psoriasis and psoriasis arthritis. Attention is however given to a novel therapeutic tool: RNA interference that controls gene silencing. This study investigates...... the efficiency of targeting TNF-a with specific short hairpin RNA (shRNA) and explores its potential in treating psoriasis. ShRNAs targeting human TNF-α mRNA were generated. Their efficiency in down-regulating TNF-a protein expression was evaluated using a Renilla luciferase screening-assay and a transient co......-transfection assay. The expression cassette encoding the most efficient TNF-a shRNA was inserted into a lentiviral vector, allowing proficient gene delivery. The lentiviral vector is integrated into the host genome and establishes life-long infection and persistent shRNA expression. The lentiviral vector expressing...

  15. The Impact of Interpersonal Style and Interpersonal Complementarity on the Therapeutic Alliance Between Therapists and Offenders in Sex Offender Treatment.

    Science.gov (United States)

    Watson, Rachael; Daffern, Michael; Thomas, Stuart

    2017-03-01

    Therapist and treatment process variables affect the effectiveness of offender rehabilitation programs. This study examined the influence of therapists' and offenders' interpersonal styles (IPSs) and interpersonal complementarity on therapeutic alliance (TA). Seventy-five sex offenders and their therapists evaluated each other's IPSs and the TA after 3 weeks of treatment. Offenders evaluated the TA more positively than therapists. Regarding the impact of IPS, therapist affiliation was positively correlated and therapist control was negatively correlated with offenders' ratings of the TA; in other words, offenders evaluated the TA more strongly when therapists were perceived as affiliative, and weaker when therapists were viewed as controlling. Offender affiliation was positively correlated with therapists' ratings of TA; in other words, therapists evaluated the TA more strongly when offenders were viewed as more affiliative; perceptions of offender control were unrelated to offenders' ratings of TA. Complementarity in IPS between offenders and therapists did not affect TA.

  16. Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Jun eWang

    2014-03-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

  17. Effect of plasma treatment on the performance of two drug-loaded hydrogel formulations for therapeutic contact lenses.

    Science.gov (United States)

    Paradiso, Patrizia; Chu, Virginia; Santos, Luís; Serro, Ana Paula; Colaço, Rogério; Saramago, Benilde

    2015-07-01

    Although the plasma technology has long been applied to treat contact lenses, the effect of this treatment on the performance of drug-loaded contact lenses is still unclear. The objective of this work is to study the effect of nitrogen plasma treatment on two drug-loaded polymeric formulations which previously demonstrated to be suitable for therapeutic contact lenses: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel loaded with levofloxacin and a silicone-based hydrogel loaded with chlorhexidine. Modifications of the surface and the optical properties, and alterations in the drug release profiles and possible losses of the antimicrobial activities of the drugs induced by the plasma treatment were assessed. The results showed that, depending on the system and on the processing conditions, the plasma treatment may be beneficial for increasing wettability and refractive index, without degrading the lens surface. From the point of view of drug delivery, plasma irradiation at moderate power (200 W) decreased the initial release rate and the amount of released drug, maintaining the drug activity. For lower (100 W) and higher powers (300 W), almost no effect was detected because the treatment was, respectively, too soft and too aggressive for the lens materials.

  18. Biostereometric Analysis Of Therapeutic Results In The Treatment Of Chronic, Progressive, Decompensating Postural Back Strain

    Science.gov (United States)

    Johnson, David M.

    1980-07-01

    A two year pilot program for biostereometric analysis of treatment effectiveness in five patients with chronic decompensating back strain has been completed. The patients came from the investigators family practice of osteopathic medicine. They all manifested objective signs of ligamentous and muscular strain of their postural biomechanics due to the combined effects of prior injury to the musculoskeletal system, gravity strain and the passage of time. Two of the patients were treated with osteopathic manipulative treatment plus a pelvic leverage treatment device developed by Martin Jungman, M.D. Two patients received osteopathic treatment alone and the fifth individual switched from control to full program status in the middle of the study after the second stereophotography recording. Signs and symptoms of all patients' gravity strain syndrome changed during the program. Those patients who had the full combination of treatment modalities showed the most positive and significant postural changes as demonstrated by the biostereometric technique developed and performed by the Department of Biostereometrics, Texas Institute of Rehabilitation and Research, Baylor College of Medicine, Houston, Texas. Improvement was clearly demonstrated more quickly than with the prior radiographic measuring methods. X-ray and other studies have also been done on this group. All of the data has not been processed yet in this program. The test patients have improved posture, muscle mass and tone, more stamina and reduced pain.

  19. [PARI-ETLD (Therapeutic Approach and Nursing Research -- Epidemiology and Treatment of Decubitus Lesions].

    Science.gov (United States)

    Di Giulio, P; Saiani, L; Laquintana, D; Palese, A; Bellingeri, A

    2001-01-01

    Pressure sores are one of the preferred nursing research topics but, in spite of the large number of studies, most questions related to the prevention and treatment of pressure sores remain unanswered. Well designed clinical trials and on sufficiently large samples are very rare and most treatments are routinely used even without a reliable evidence of their efficacy. The PARI-ETLD trial is the occasion for: a. evaluating the efficacy of the Fitostimoline, in the ri-epitelization of superficial pressure sores; b. starting a clinical trial conducted by nurses; c. building a multicentre nursing network for collecting data on the epidemiology of pressure sores and for evaluating the effectiveness of caring strategies and treatments. The protocol presented, with the data collection forms, is an example of feasibility of clinical trials in the nursing practice and offers examples of ways for overcoming common problems related to the implementation of clinical trials in everyday practice.

  20. Nonsurgical treatment of hemifacial microsomia by therapeutic ultrasound and hybrid functional appliance

    Directory of Open Access Journals (Sweden)

    Tarek El-Bialy

    2010-03-01

    Full Text Available Tarek El-Bialy1, Ali Hasan2, Ahmad Janadas3, Tarik Albaghdadi41Division of Orthodontics, Department of Dentistry, University of Alberta, Edmonton, Alberta, Canada; 2Division of Orthodontics, Department of Preventive Dental Sciences, Faculty of Dentistry; 3Division of Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry; 4Division of Radiology, Faculty of Medicine, King Abdul Aziz University, Jeddah, Saudi ArabiaAim: Conventional treatment of patients with hemifacial microsomia involves orthognathic surgery and/or distraction osteogenesis of the mandible. Previous reports showed that low-intensity pulsed ultrasound (LIPUS enhances mandibular growth in growing rabbits and monkeys. In monkeys, LIPUS enhanced mandibular growth when combined with functional jaw orthopedic appliances. The purpose of this pilot study was to investigate if LIPUS could enhance mandibular growth in children with hemifacial microsomia.Methods: Five children (age range 3–11 years with hemifacial microsomia were treated with hybrid jaw orthopedic functional appliances and treatment of the affected mandibular condyle by LIPUS for 20 minutes per day.Results: The results showed that after one year of treatment, significant improvement of the underdeveloped side of patients’ faces and mandibles was recognized both clinically and radiographically.Discussion: Although improvement took a longer time than did a surgical approach, optimizing this technique may achieve better results in a shorter treatment time. A randomized controlled clinical trial to investigate the effect of optimized LIPUS application or functional appliances in the treatment of hemifacial microsomia is warranted.Keywords: hemifacial microsomia, LIPUS, non-surgical treatment, children

  1. New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency.

    Science.gov (United States)

    Azizi, G; Abolhassani, H; Yazdani, R; Mohammadikhajehdehi, S; Parvaneh, N; Negahdari, B; Mohammadi, J; Aghamohammadi, A

    2017-09-01

    Purpose. To report the successful use of sirolimus for management of enteropathy in four patients with LPS-responsive beige-like anchor protein (LRBA) deficiency. Methods. Case series. Results. sirolimus therapy led to a complete improvement of symptoms including decrease in frequency and severity of diarrhea, as well as patients' weight gain. No signs of abdominal cramps and anorexia were also detected during the follow up period after treatment. Conclusions. sirolimus with its potential efficacy and immunomodulatory properties may be recommended for the treatment of severe enteropathy refractory to conventional therapy in patients with LRBA deficiency.

  2. Therapeutic effect of the laser system Prometeus in the treatment of vertebrogenic lumboradiculalgia.

    Science.gov (United States)

    Toshev, I; Gozmanov, G; Kitov, B; Madzhurov, P

    1992-01-01

    The authors report their experience in the application of laser therapy using 904 nm laser irradiation and impulse power of 10 W on patients with vertebrogenic lumboradiculalgia (osteochondrosis and herniation of the intervertebral disk). The therapeutic effect of the PROMETEUS type laser system is compared to that of similar equipment reported in literature. Pain was usually relieved between days five and 10 of laser therapy, or, in cases of slower convalescence, by day 15. Clinical symptoms of the disorders also disappeared simultaneously with the alleviation of pain. Our results are similar to those obtained by A.S. Krjuk (1986) and S. Gatev (1985), better than those of Van Lyancin (1988) and worse than those of D. Milani (1987). Laser therapy produces no side effects. It is an important contribution to the armamentarium of modern physiotherapeutic methods. When it is administered properly, it is painless, aseptic and does not cause trauma or allergic reactions. Moreover, it reduces the usage of drugs and consumable materials.

  3. Treatment of infertility associated with deep endometriosis: definition of therapeutic balances.

    Science.gov (United States)

    Somigliana, Edgardo; Garcia-Velasco, Juan Antonio

    2015-10-01

    Deep endometriosis is a demanding condition that is associated with infertility. However, evidence supporting a direct link between deep endometriosis and infertility is weak. In fact, infertility in affected patients is more likely to be explained by the strong association between deep endometriosis and adhesions, superficial endometriotic implants, ovarian endometriomas, and adenomyosis. The purported beneficial effects of surgery on infertility are mainly based on the 40%-42% pregnancy rate (PR) after surgery observed in published case series. However, this level of evidence is questionable and overestimates the benefits of the intervention. Even if comparative studies are lacking, IVF may be a valid alternative. The procedure may be less effective in affected women compared with other indications and it is not without additional deep endometriosis-related risks. Some case reports suggest that lesions might progress during IVF causing ureteral or intestinal complications or can decidualize during pregnancy causing intestinal perforation, pneumothorax, and pelvic vessels rupture. Finally, in the decision-making process, physicians should also consider that women with a history of deep endometriosis may face an increased risk of pregnancy complications. In conclusion, clear recommendation for the management of infertile women with deep endometriosis cannot be extrapolated from the literature. The therapeutic decision should be based on a comprehensive evaluation that includes clinical history, instrumental findings, pain symptoms, risks of pregnancy complications, and the woman's wishes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Sadia Afrin

    2016-01-01

    Full Text Available Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases. In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer.

  5. Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.

    Science.gov (United States)

    Pearn, Matthew L; Niesman, Ingrid R; Egawa, Junji; Sawada, Atsushi; Almenar-Queralt, Angels; Shah, Sameer B; Duckworth, Josh L; Head, Brian P

    2016-07-06

    Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.

  6. Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment.

    Science.gov (United States)

    Afrin, Sadia; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Varela-López, Alfonso; Quiles, José L; Mezzetti, Bruno; Battino, Maurizio

    2016-01-01

    Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer.

  7. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

    Science.gov (United States)

    Milne, Jill C.; Lambert, Philip D.; Schenk, Simon; Carney, David P.; Smith, Jesse J.; Gagne, David J.; Jin, Lei; Boss, Olivier; Perni, Robert B.; Vu, Chi B.; Bemis, Jean E.; Xie, Roger; Disch, Jeremy S.; Ng, Pui Yee; Nunes, Joseph J.; Lynch, Amy V.; Yang, Hongying; Galonek, Heidi; Israelian, Kristine; Choy, Wendy; Iffland, Andre; Lavu, Siva; Medvedik, Oliver; Sinclair, David A.; Olefsky, Jerrold M.; Jirousek, Michael R.; Elliott, Peter J.; Westphal, Christoph H.

    2009-01-01

    Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes1,2. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity3–9. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival10–14. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme—peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes. PMID:18046409

  8. The scatter factor signaling pathways as therapeutic associated target in cancer treatment.

    Science.gov (United States)

    Accornero, P; Pavone, L M; Baratta, M

    2010-01-01

    Receptor tyrosine kinases (RTKs) are key regulators of critical cellular processes such as proliferation, differentiation, neo-vascularization, and tissue repair. In addition to their importance in the regulation of normal physiology, aberrant expression of certain RTKs has also been associated to the development and progression of many types of cancer. c-Met and RON are two RTKs with closely related sequences, structural homology, and similar functional properties. Both these receptors, once activated by their respective ligands, the Hepatocyte Growth Factor/Scatter Factor (HGF/SF1) and the Macrophage Stimulating Protein/Scatter Factor 2 (MSP/SF2), can induce cell migration, invasion and proliferation. Soon after its discovery in the mid-1980s, c-Met attracted a great interest because of its role in modulating cell motility. Moreover, the causal role for c-Met activating mutations in human cancer propelled an intensive drug discovery effort throughout academic institutions and pharmaceutical companies. While c-Met is now a well-accepted target for anticancer drug design, less is known about the role of RON in cancer and less has been done to target this receptor. In this review we will discuss the biological relevance of c-Met and RON, their deregulation in human cancers and the progress, so far, in identifying c-Met and RON signaling inhibitors. Finally, we will focus on the development of therapeutic strategies and drug efficacy studies based on interfering the scatter factor signaling pathways.

  9. The development of virtual reality therapy (VRT) system for the treatment of acrophobia and therapeutic case.

    Science.gov (United States)

    Jang, Dong P; Ku, Jeong H; Choi, Young H; Wiederhold, Brenda K; Nam, San W; Kim, In Y; Kim, Sun I

    2002-09-01

    Virtual reality therapy (VRT), based on this sophisticated technology, has been recently used in the treatment of subjects diagnosed with acrophobia, a disorder that is characterized by marked anxiety upon exposure to heights and avoidance of heights. Conventional VR systems for the treatment of acrophobia have limitations, over-costly devices or somewhat unrealistic graphic scenes. The goal of this study was to develop an inexpensive and more realistic virtual environment (VE) in which to perform exposure therapy for acrophobia. It is based on a personal computer, and a virtual scene of a bunge-jump tower in the middle of a large city. The virtual scenario includes an open lift surrounded by props beside a tower, which allows the patient to feel a sense of heights. The effectiveness of the VE was evaluated through the clinical treatment of a subject who was suffering from the fear of heights. As a result, it was proved that this VR environment was effective and realistic at overcoming acrophobia according not only to the comparison results of a variety of questionnaires before and after treatment but also to the subject's comments that the VE seemed to evoke more fearful feelings than the real situation.

  10. Ultrasound Evaluation of Congenital Cervical Teratoma and Therapeutic Management (Ex Utero Intrapartum Treatment)

    Science.gov (United States)

    Padilla Iserte, Pablo; Sanroma Pérez, Amparo; Ferri Folch, Blanca; Rubio Moll, Juan; Diago Almela, Vicente; Perales-Marín, Alfredo

    2012-01-01

    The ultrasound evaluation of the fetal neck has a high importance as a key point of the airway and digestive tract. We report the case of a fetus diagnosed with a cervical teratoma by ultrasound, which generated a compressive effect on airway, requiring a surgical approach EXIT (ex utero intrapartum treatment) to ensure the extrauterine viability. PMID:23320215

  11. Ultrasound Evaluation of Congenital Cervical Teratoma and Therapeutic Management (Ex Utero Intrapartum Treatment

    Directory of Open Access Journals (Sweden)

    Pablo Padilla Iserte

    2012-01-01

    Full Text Available The ultrasound evaluation of the fetal neck has a high importance as a key point of the airway and digestive tract. We report the case of a fetus diagnosed with a cervical teratoma by ultrasound, which generated a compressive effect on airway, requiring a surgical approach EXIT (ex utero intrapartum treatment to ensure the extrauterine viability.

  12. Biofeedback as complementary treatment in patients with epilepsy – an underestimated therapeutic option? Review, results, discussion

    Directory of Open Access Journals (Sweden)

    Uhlmann Carmen

    2016-12-01

    Full Text Available Background. Biofeedback methods represent side effect free complementary options in the treatment of epilepsy. In this paper we review the current status of these methods in terms of clinical study results and their evaluation by systematic review papers. Possible mechanisms of action in biofeedback methods are discussed.

  13. Therapeutic drug monitoring : how to improve drug dosage and patient safety in tuberculosis treatment

    NARCIS (Netherlands)

    Sotgiu, Giovanni; Alffenaar, Jan-Willem C.; Centis, Rosella; D'Ambrosio, Lia; Spanevello, Antonio; Piana, Andrea; Migliori, Giovanni Battista

    2015-01-01

    In this article we describe the key role of tuberculosis (TB) treatment, the challenges (mainly the emergence of drug resistance), and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contrib

  14. Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

    Science.gov (United States)

    Abdel-Raheem, Talal A; Méabed, Eman M H; Nasef, Ghada A; Abdel Wahed, Wafaa Y; Rohaim, Rania M A

    2016-10-01

    The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 μg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient.

  15. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future.

    Science.gov (United States)

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

  16. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2016-01-01

    Full Text Available Objective. Spinal cord injury (SCI is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI, as well as from master’s dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

  17. A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90α

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Adi; Shervington, Leroy; Munje, Chinmay; Shervington, Amal, E-mail: aashervington@googlemail.com [Brain Tumour North West, Faculty of Science and Technology, University of Central Lancashire, Preston, PR1 2HE (United Kingdom)

    2011-12-08

    Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy.

  18. Review of therapeutic options for adjuvant treatment of focal seizures in epilepsy: focus on lacosamide.

    Science.gov (United States)

    Becerra, Juan Luis; Ojeda, Joaquín; Corredera, Enrique; Ruiz Giménez, Jesús

    2011-12-05

    Epilepsy is one of the most common serious neurological conditions worldwide, with an age-adjusted incidence of approximately 50 per 100,000 persons per year in developed countries. Antiepileptic therapy can result in long-term remission in 60-70% of patients, but many patients will require combination treatment to achieve optimal seizure control, as monotherapy is ineffective at controlling seizures in 30-53% of patients. Despite the increase in available treatment options, patient outcomes have not improved significantly and there is still a need for more effective therapies. Drugs used in the treatment of focal-onset seizures are a diverse range of compounds, and in most cases their mechanism of action is unknown or poorly defined. This review discusses the efficacy and safety of the newer adjuvant antiepileptic therapies that may improve outcomes in patients unresponsive to monotherapy, including clobazam, vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam, oxcarbazepine, pregabalin, zonisamide and eslicarbazepine, with focus on lacosamide. Lacosamide has been shown to exert its anticonvulsant effects predominantly by enhancement of the slow inactivation of voltage-gated sodium channels. Lacosamide is indicated for use as adjuvant treatment of focal-onset seizures in patients with epilepsy, and there is some evidence that it may also be of use in patients with status epilepticus and cancer patients with epilepsy. The efficacy of lacosamide has been assessed in three randomized, double-blind, placebo-controlled clinical trials, all of which have shown lacosamide to be effective at reducing seizure frequency and increasing 50% responder rates in patients with focal-onset seizures. Long-term lacosamide treatment is generally well tolerated and is not associated with significant drug interactions; the availability of an intravenous form of the drug also makes it particularly useful for a broad range of patients.

  19. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia

    Directory of Open Access Journals (Sweden)

    Bacha Ketema

    2011-03-01

    Full Text Available Abstract Background Chloroquine is an anti-malarial drug being used to treat Plasmodium vivax malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against P. vivax strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR of South Ethiopia Results Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR. However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients, day 14 (six patients, and day 21 (one patient. The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/μl was higher than day of recurrence (372.37/μl. Parasite reduction ratio (PRR of treatment failure cases was 12.6/μl. Conclusion This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217] as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant P. vivax (CRPv strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.

  20. Therapeutic eyelids hygiene in the algorithms of prevention and treatment of ocular surface diseases

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2016-01-01

    Full Text Available When acute inflammation in anterior eye segment of a forward piece of an eye was stopped, ophthalmologists face a problem of absence of acute inflammation signs and at the same time complaints to the remain discomfort feelings. It causes dissatisfaction from the treatment. The complaints are typically caused by disturbance of tears productions. No accidental that the new group of diseases was allocated — the diseases of the ocular surface. Ocular surface is a difficult biologic system, including epithelium of the conjunctiva, cornea and limb, as well as the area costal margin eyelid and meibomian gland ducts. Pathological processes in conjunctiva, cornea and eyelids are linked with tears production. Ophthalmologists prescribes tears substitutions, providing short-term relief to patients. However, in respect that the lipid component of the tear film plays the key role in the preservation of its stability, eyelids hygiene is the basis for the treatment of dry eye associated with ocular surface diseases. Eyelids hygiene provides normal functioning of glands, restores the metabolic processes in skin and ensures the formation of a complete tear film. Protection of eyelids, especially the marginal edge from aggressive environmental agents, infections and parasites and is the basis for the prevention and treatment of blepharitis and dry eye syndrome. The most common clinical situations and algorithms of their treatment and prevention of dysfunction of the meibomian glands; demodectic blepharitis; seborrheic blepharitis; staphylococcal blepharitis; allergic blepharitis; barley and chalazion are discussed in the article. The prevention keratoconjunctival xerosis (before and postoperative period, caused by contact lenses, computer vision syndrome, remission after acute conjunctiva and cornea inflammation is also presented. The first part of the article presents the treatment and prevention algorithms for dysfunction of the meibomian glands, as well as

  1. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value.

    Science.gov (United States)

    Zoons, E; Dijkgraaf, M G W; Dijk, J M; van Schaik, I N; Tijssen, M A

    2012-12-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharmaco-therapeutic and pharmaco-economic value of botulinum toxin as treatment for focal dystonia, which yielded the following results. Botulinum toxin is the most effective treatment for reducing dystonic symptoms measured with dystonia-specific and general questionnaires, and pain in patients with focal dystonia. Seventy-one percent of patients with cervical dystonia had a reduction in neck pain compared to 12 % in placebo groups. Adverse events occur in 58 % of patients during treatment with botulinum toxin compared to 46 % treated with placebo. Especially dry mouth, neck weakness, dysphagia, and voice changes are common. Adverse events are usually mild and self-limiting. Health-related quality of life, measured with the SF-36 is 20-50 points lower in patients with focal dystonia compared to controls and the effect of botulinum toxin on health-related quality of life is unclear. Botulinum toxin treatment is expensive because the drug itself is expensive. Yearly costs for treating a patient with focal dystonia with botulinum toxin range from EUR 347 to EUR 3,633 and the gain in QALYs with BTX treatment is small. Focal dystonia impairs the productivity and the ability to work. At start of botulinum toxin treatment only 47-50 % was working. Botulinum toxin partly improves this. Overall, we conclude that botulinum toxin is an expensive drug with good effects. From a societal perspective, the costs may well weigh up to the regained quality of life. However, the available literature concerning costs, health-related quality of life and labor participation is very limited. An extensive cost-effectiveness study should be performed incorporating all these aspects.

  2. [Proprioceptive neuromuscular facilitation method of therapeutic rehabilitation in the treatment of patients with Parkinson disease].

    Science.gov (United States)

    Mirek, Elzbieta; Chwała, Wiesław; Longawa, Krystyna; Rudzińska, Monika; Adamkiewicz, Paweł; Szczudlik, Andrzej

    2003-01-01

    Planning and verification of progress of efficacious physiotherapeutic effect on Parkinson's disease depends notably on the right identification of areas and scope of dysfunction of motoric systems. Biomechanical evaluation of motoric organ disability made by means of three-dimensional motion analysis using the "Vicon" system can make it considerably easier. A sample of three patients (two women and one man of average age of sixty-four) with idiopathic parkinsonism has been examined for the purpose of this evaluation. Based upon results of the three-dimensional motion analysis of these patients, dominant individual movement disorders were determined and individual therapeutic rehabilitation using the PNF method was planned. Within therapy, using the PNF method, they applied special techniques using motor patterns for the pelvis, upper and lower limbs in order to improve movement through an approach of assessed parameters to the biomechanical standard. After three weeks of therapy, specific characteristics of gait were examined again. On the basis of research results before therapy, it was found that these patients had none or limited scope of plantar flexion of feet, excessive dorsal flexion of feet, lengthened duration of stance phase, considerable excessive external rotation of shanks and excessive anteversion of the pelvis during gait cycle. Also big differences in values for spatiotemporal parameters (such as walking speed and frequency, stride length and time of single limb support) between the patients and healthy people were observed. After therapy, there has not been a marked variability in the scope of angular changes to the above-mentioned dysfunction. Only proportions between the duration of stance phase and swing phase have improved noticeably, so that they have directly resulted in better rhythm of gait. They have considerably approached the standards of frequency and speed (p = 0.05). However, stride length and duration of single limb support has not

  3. Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment.

    Science.gov (United States)

    Alzohairy, Mohammad A

    2016-01-01

    Neem (Azadirachta indica) is a member of the Meliaceae family and its role as health-promoting effect is attributed because it is rich source of antioxidant. It has been widely used in Chinese, Ayurvedic, and Unani medicines worldwide especially in Indian Subcontinent in the treatment and prevention of various diseases. Earlier finding confirmed that neem and its constituents play role in the scavenging of free radical generation and prevention of disease pathogenesis. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-κB, PI3K/Akt, Bcl-2, and VEGF. It is considered as safe medicinal plants and modulates the numerous biological processes without any adverse effect. In this review, I summarize the role of Azadirachta indica in the prevention and treatment of diseases via the regulation of various biological and physiological pathways.

  4. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    OpenAIRE

    Ciechomska, Marzena; O'Reilly, Steven

    2016-01-01

    Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic...

  5. Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer

    Science.gov (United States)

    2009-07-01

    matched normal donor, has developed into a highly effective therapy for the treatment of hematological malignancies. The canine model has played a...palpation. We employed both of these techniques, performed with the aid of a veterinarian , to determine whether BPH was evident after a DLI of...a veterinarian on day 21 and 47 by rectal palpation. Together, these data suggest there was no indication of BPH based on prostate enlargement

  6. Substituted benzothiazoles and therapeutic uses thereof for the treatment of human diseases

    OpenAIRE

    Martínez, Ana; Pérez Fernández, Daniel Ignacio; Gil Ayuso-Gontán, Carmen; García Salado, Irene; Redondo, Miriam; Pérez, Concepción

    2013-01-01

    [EN] The invention relates to a family of differently substituted benzothiazoles having an inhibitory activity against the enzyme casein kinase 1 (CK1), as a result of which they are suitable for use in the treatment or prevention of diseases caused by this enzyme, particularly diseases associated with circadian rhythm and inflammatory, autoimmune, psychiatric, neurodegenerative, neurological or ophthalmological diseases, as well as for inducing cell regeneration.

  7. Prospects of Developing Medicinal Therapeutic Strategies and Pharmaceutical Design for Effective Gluten Intolerance Treatment.

    Science.gov (United States)

    Savvateeva, Lyudmila V; Zamyatnin, Andrey A

    2016-01-01

    Gluten intolerance is an umbrella term for gluten-related disorders manifested in health decline as a result of the gluten ingestion. The spectrum of gluten-related disorders includes three major groups: autoimmune (mainly, Celiac Disease, CD, also known as Celiac Sprue, dermatitis herpetiformis, or gluten-sensitive ataxia), allergic (wheat allergy, WA), and non-autoimmune non-allergic (non-celiac gluten sensitivity, NCGS, or gluten sensitivity, GS). Pathogenesis and diagnostics of CD and WA are well established in contrast to NCGS, pathogenicity of which is still poorly understood and its symptoms are frequently misdiagnosed since most of the NCGS cases are currently identified via the process of CD and WA exclusion. By now, the only one proven effective way for CD treatment is gluten-free diet (GFD). However, such an increasingly gaining popularity diet is apparently unsuitable for NCGS treatment because in this case gluten does not always arise as the major or exclusive culprit of gastrointestinal disorder. Furthermore, it is some physicians' opinion that GFD can be deficient in fiber and in other vitamins and minerals. In many cases, GFD is commercially inaccessible for the most needy, whereas strict adherence to the diet is complicated by the presence of small amounts of the gluten components in some foods and even medicines. In this regard, a number of research groups and pharmaceutical companies are extensively developing alternative medicinal approaches to GFD for effective gluten intolerance treatment. This review summarizes our understanding of gluten-related disorders, possible mechanisms of gluten intolerance activation and advantages of gluten intolerance medicinal treatment using novel drug candidates obtained with a proper pharmaceutical design.

  8. The Therapeutic Benefit of Allopurinol in the Treatment of Foreign Body Granulomas Caused by Polymethylmethacrylate Microspheres

    Directory of Open Access Journals (Sweden)

    Luisa Kelmer Côrtes de Barros Silveira

    2012-01-01

    Full Text Available Injectable polymethylmethacrylate (PMMA microspheres are nonbiodegradable and too large for macrophage phagocytosis. There are several complications possible to happen, like chronic nonspecific inflammatory reactions, lip stiffness, infection, and granulomas. The occurrence of granulomas can lead to a not aesthetic result, making some extreme changes in the patient’s life. The objective of this case report is to describe the successful treatment of foreign body granulomas caused by polymethylmethacrylate microspheres using allopurinol, an innovative therapy for this condition.

  9. Advances in adult asthma diagnosis and treatment in 2012: potential therapeutics and gene-environment interactions.

    Science.gov (United States)

    Apter, Andrea J

    2013-01-01

    In the Journal of Allergy and Clinical Immunology in 2012, research reports related to asthma in adults clustered around mechanisms of disease, with a special focus on their potential for informing new therapies. There was also consideration of the effect of the environment on health from pollution, climate change, and epigenetic influences, underlining the importance of understanding gene-environment interactions in the pathogenesis of asthma and response to treatment.

  10. Effectiveness of therapeutic physical exercise in the treatment of patellofemoral pain syndrome: a systematic review

    OpenAIRE

    2015-01-01

    [Purpose] The aim of this study was to analyze the effectiveness of conservative treatment of patellofemoral pain syndrome with physical exercise. [Subjects and Methods] A computer-based review conducted of four databases (PubMed, the Cochrane Library, PEDro, and the University Library) was completed based on the inclusion criteria of patellofemoral pain syndrome patients treated with physical exercise methods and examination with self-reported pain and/or functional questionnaires. [Results]...

  11. Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Liang Ma

    2013-08-01

    Full Text Available Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β, and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952 and type II (ARK1 endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth.

  12. Current and developing therapeutic agents in the treatment of Chagas disease

    Directory of Open Access Journals (Sweden)

    Werner Apt

    2010-09-01

    Full Text Available Werner AptUniversity of Chile, Faculty of Medicine, Santiago, ChileAbstract: Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF and benznidazole (BNZ are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30–60 days. Other useful drugs are itraconazole and posaconazole. The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished. At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease. In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.Keywords: Chagas disease, treatment, nifurtimox, benznidazole, allopurinol, itraconazole, posaconazole

  13. Traditional Chinese medicine valuably augments therapeutic options in the treatment of climacteric syndrome.

    Science.gov (United States)

    Eisenhardt, Sarah; Fleckenstein, Johannes

    2016-07-01

    Climacteric syndrome refers to recurring symptoms such as hot flashes, chills, headache, irritability and depression. This is usually experienced by menopausal women and can be related to a hormonal reorganization in the hypothalamic-pituitary-gonadal axis. In Traditional Chinese Medicine, originating 1000s of years ago, above-mentioned symptoms can be interpreted on the basis of the philosophic diagnostic concepts, such as the imbalance of Yin and Yang, the Zang-Fu and Basic substances (e.g. Qi, Blood and Essence). These concepts postulate balance and harmonization as the principle aim of a treatment. In this context, it is not astounding that one of the most prominent ancient textbooks dating back to 500-200 BC, Huang di Neijing: The Yellow Emperor's Classic of Internal Medicine gives already first instructions for diagnosis and therapy of climacteric symptoms. For therapy, traditional Chinese medicine comprises five treatment principles: Chinese herbal medicine, TuiNa (a Chinese form of manual therapy), nutrition, activity (e.g. QiGong) and acupuncture (being the most widespread form of treatment used in Europe). This review provides an easy access to the concepts of traditional Chinese medicine particularly regarding to climacteric syndrome and also focuses on current scientific evidence.

  14. New and emerging therapeutic agents for the treatment of fibromyalgia: an update

    Directory of Open Access Journals (Sweden)

    Jill M Recla

    2010-07-01

    Full Text Available Jill M ReclaIGERT Program in Functional Genomics, Graduate School of Biomedical Sciences, University of Maine and The Jackson Laboratory, Bar Harbor, Maine, USAAbstract: Fibromyalgia (FM is a chronic widespread pain condition that is estimated to affect5 million US adults. Several molecular pathophysiologies are thought to contribute to the symptoms of FM, complicating the development of effective clinical management techniques. It is now known that abnormalities in both nociceptive and central pain processing systems are necessary (but perhaps not sufficient to condition the onset and maintenance of FM, producing associated neuropsychologic symptoms such as pronounced fatigue, sleep abnormalities, cognitive difficulties, stress sensitivity, anxiety, and depression. Current treatment strategies are focused primarily on correcting the pathophysiologic mechanisms underlying these nervous system abnormalities. Clinical studies demonstrate the safety and efficacy of three drugs recently approved for the treatment of FM: pregabalin (an alpha-2-delta ligand, and duloxetine and milnacipran (serotonin/norepinephrine reuptake inhibitors. This review describes these pharmaceuticals in detail and discusses their current roles in FM management.Keywords: fibromyalgia, treatment, pharmacotherapy, pregabalin, duloxetine, milnacipran

  15. [Diagnosis and treatment of varicose veins: part 2: therapeutic procedures and results].

    Science.gov (United States)

    Nüllen, H; Noppeney, T

    2010-12-01

    This is the second of two articles on the diagnosis and treatment of varicose veins. Primary varicosis is a congenital degenerative disease of the peripheral venous system of the lower extremities. Treatment is carried out according to an individualized concept which takes the incurability and progression of the disease into consideration. Conservative treatment with compression bandages is an option for all forms of varicosis and the accompanying complications. Veins can be specifically ablated by sclerotherapy of varices. In addition to high ligation and stripping mini-phlebectomy and subfascial endoscopic perforator surgery (SEPS) can also be performed. The indications in cases of SEPS should be extremely limited because of possible severe complications. Radiofrequency ablation (RFO) and endovenous laser therapy (ELT) are also available as endovenous therapy options. Information in the literature on recurrence rates of the various procedures is extremely variable and the reasons for recurrent varicosis are the subject of controversy. The data relating to the results of RFO and ELT are relatively good and both procedures show a significant improvement in quality of life and the venous clinical severity score (VCSS).

  16. Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis.

    Science.gov (United States)

    Badea, I; Taylor, M; Rosenberg, A; Foldvari, M

    2009-03-01

    SSc is a chronic progressive disorder of unknown aetiology characterized by excess synthesis and deposition of collagen and other extracellular matrix components in a variety of tissues and organs. Localized scleroderma (LS) differs from SSc in that with LS only skin and occasionally subcutaneous tissues are involved. Although rarely life threatening, LS can be disfiguring and disabling and, consequently, can adversely affect quality of life. There is no known effective treatment for LS, and various options, including, as examples, corticosteroids and other immunomodulatory agents, ultraviolet radiation and vitamin D analogues, are of unproven efficacy. Clinical trials evaluating combination therapy such as corticosteroids with MTX or UVA1 exposure with psoralens have not been established as consistently effective. New immunomodulators such as tacrolimus and thalidomide are also being evaluated. A better understanding of the molecular and cellular mechanisms of LS has led to evaluation of new treatments that modulate profibrotic cytokines such as TGF-beta and IL-4, regulate assembly and deposition of extracellular matrix components, and restore Th1/Th2 immune balance by administering IL-12 or IFN-gamma. IFN-gamma acts by directly inhibiting collagen synthesis and by restoring immune balance. In this review, we evaluate current and future treatment options for LS and cutaneous involvement in SSc. Recent advances in therapy focus mainly on anti-fibrotic agents. Delivery of these drugs into the skin as the target tissue might be a key factor in developing more effective and safer therapy.

  17. Yoga as the "next wave" of therapeutic modalities for treatment of insomnia.

    Science.gov (United States)

    Kennedy, Sarah L

    2014-01-01

    Insomnia rates continue to rise, especially among specific populations. Current nonpharmacological treatments rely primarily upon cognitive behavioral therapy for insomnia (CBT-I), which was introduced in the 1970s. Newer treatments have incorporated CBT "third wave" techniques, including mindfulness and acceptance techniques. Yoga practice is well suited to complement existing therapies and to address sleep problems in a more holistic way. Current theoretical and empirical approaches to treating insomnia are discussed, with an emphasis on the role of yoga in addressing precipitating and perpetuating factors in insomnia that have previously been largely overlooked.An estimated one-third of U.S. adults suffer from insomnia (Chen, Gelaye, & Williams, 2013; Mellinger, Balter, & Uhlenhuth, 1985; Ohayon, 2002), and the problem appears to be growing. While treatment for insomnia has helped to alleviate the problem for some (Irwin, Cole, & Nicassio, 2006; Morin et al., 2009), prevalence of insomnia is on the rise, especially among certain groups, including elderly and military populations (Morin, 2009; Mysliwiec et al., 2013). Rising rates of insomnia have been attributed to changes in lifestyle and environmental factors, including increased reliance on technology and decreased synchrony with natural wake-sleep rhythms (Brahinsky, 2013; Wallace-Guy et al., 2002; Yun, Bazar, Gerber, Lee, & Daniel, 2005).

  18. Study and evaluation of radiometry in photo therapeutic treatment of the neonatal hyperbilirubinaemia; Estudo e avaliacao da radiometria no tratamento fototerapico da hiperbilirrubinemia neonatal

    Energy Technology Data Exchange (ETDEWEB)

    Caly, Jose Pucci

    2009-07-01

    Phototherapy is a procedure established more than 50 years ago in the treatment of the newborn jaundice. However there is no a standard method to quantify the photo therapeutic dose in published clinical studies, hindering the comparison of previous studies on photo therapeutic effectiveness, as well as the establishment of safe and predictable doses. The photo therapeutic dose depends, among other factors, on the effective mean irradiance produced by the photo therapeutic unit. There are no standard procedures, however, neither to quantify the effective irradiance, nor to estimate the mean effective irradiance. As a consequence, large measurement variations in a same photo therapeutic unit are observed using different commercially available radiometers, as a consequence of the vast diversity of spectral responsivities of the instruments. An objective of this work was to adapt and to apply the bases of the wideband ultraviolet radiometry to quantify the available irradiance from photo therapeutic units, establishing procedures that allow us to compare measured irradiances from different sources, using radiometers presenting different spectral responsivities. Another objective was to characterize samples of photo therapeutic units commonly used, focusing the problem of the estimation of the effective mean irradiance from photo therapeutic units, proposing a method to estimate of the effective irradiance from focused sources. The experimental results allow us to conclude that it is not only necessary to standardize the photo therapeutic radiometry, but also the method of estimation of the effective mean irradiance. (author)

  19. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    Science.gov (United States)

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  20. Suction-irrigation drainage: an underestimated therapeutic option for surgical treatment of deep sternal wound infections†

    Science.gov (United States)

    Deschka, Heinz; Erler, Stefan; El-Ayoubi, Lemir; Vogel, Cordula; Vöhringer, Luise; Wimmer-Greinecker, Gerhard

    2013-01-01

    OBJECTIVES Deep sternal wound infections are significant and severe complications following cardiac surgery and substantially influence perioperative morbidity and mortality. We present the experience of our department using two different surgical treatments over a three-year period. METHODS Between January 2009 and December 2011, a total of 3274 cardiac procedures with complete median sternotomy were performed in our department. In 94 patients (3%), a deep sternal wound infection occurred, including sternal instability with consecutive surgical treatment. The patients either received wound debridement with sternum refixation and suction-irrigation drainage (SID; n = 72) or sternum refixation only (RF; n = 22) if there was sternal instability with limited signs of infection. SID was routinely installed for 7 days: the irrigation solution contained neomycin. In all cases, swabs were taken and analysed. The different methods were evaluated in respect of their clinical outcomes. RESULTS The success rate—defined as single, uncomplicated procedure—of the SID treatment was 74%, compared with 59% of the isolated sternum refixation. Complications included continuous infection, recurrence of sternal instability and wound necrosis. Eighty-eight percent of the swabs in the SID group were positive, compared with 32% in the sternal refixation only group. The dominating pathogenic germs were coagulase-negative staphylococci and staphylococcus aureus. Mortality was 10% for the SID group and 5% for the RF group. CONCLUSIONS Contrary to accepted opinion, the suction-irrigation drainage is an appropriate therapy for deep sternal wound infections. Nevertheless, deep sternal wound infections after cardiac surgery remain severe complications and are related to increased morbidity and mortality. PMID:23529753

  1. [Craniopharyngioma in children: importance of a multidisciplinary approach and therapeutic strategies in the treatment of relapsing].

    Science.gov (United States)

    Fiorito, C M M; Giglione, E; Bellone, S; Peretta, P; Bertin, D; Basso, M E; Bona, G

    2013-12-01

    The craniopharyngioma is a benign intracranial nonglial tumor derived from a malformation of the embryonic tissue. Represents approximately 6-9% of brain tumors in children. It grows close to the optic nerve, hypothalamus and pituitary. The most frequent histological variety in children is adamantinomatous. The initial symptoms of intracranial hypertension is headache and nausea, followed by visual disturbances, impaired hormonal changes such as the secretion of GH, gonadotropins, TSH and ACTH and central diabetes insipidus. We present the clinical case of MD, 5yrs at age, which shows signs of intracranial hypertension syndrome: neuroradiological findings raise the diagnosis of adamantinomatous craniopharyngioma for which the child underwent to sub-total surgical removal of the lesion and radiosurgery treatment. During the disease develops visual impairment, and secondary diabetes insipidus, hypothyroidism hipocotisolism that takes therapy with desmopressin (Minirin), Cortone acetate and L-tiroxine. For the failure of previous therapies, the child has performed chemotherapy with cisplatin (30 mg/sqm/day) and Etoposide (150 mg/mq/day). A year after the end of the last cycle of chemotherapy was detected new progression of the lesion with the appearance of worsening headache and vomiting in the upright position. TC notes the expansion of the third ventricle and the patient undergoes surgery craniotomy. This clinical case underlines the difficulties in treatment of recurrent craniopharyngioma in situations where the anatomical location do not permit aggressive radical surgery. Anyway, new studies are needed to evaluate the effectiveness of systemic chemotherapy as a method of experimental treatment that could reduce the progression of disease.

  2. Suction-irrigation drainage: an underestimated therapeutic option for surgical treatment of deep sternal wound infections.

    Science.gov (United States)

    Deschka, Heinz; Erler, Stefan; El-Ayoubi, Lemir; Vogel, Cordula; Vöhringer, Luise; Wimmer-Greinecker, Gerhard

    2013-07-01

    Deep sternal wound infections are significant and severe complications following cardiac surgery and substantially influence perioperative morbidity and mortality. We present the experience of our department using two different surgical treatments over a three-year period. Between January 2009 and December 2011, a total of 3274 cardiac procedures with complete median sternotomy were performed in our department. In 94 patients (3%), a deep sternal wound infection occurred, including sternal instability with consecutive surgical treatment. The patients either received wound debridement with sternum refixation and suction-irrigation drainage (SID; n = 72) or sternum refixation only (RF; n = 22) if there was sternal instability with limited signs of infection. SID was routinely installed for 7 days: the irrigation solution contained neomycin. In all cases, swabs were taken and analysed. The different methods were evaluated in respect of their clinical outcomes. The success rate-defined as single, uncomplicated procedure-of the SID treatment was 74%, compared with 59% of the isolated sternum refixation. Complications included continuous infection, recurrence of sternal instability and wound necrosis. Eighty-eight percent of the swabs in the SID group were positive, compared with 32% in the sternal refixation only group. The dominating pathogenic germs were coagulase-negative staphylococci and staphylococcus aureus. Mortality was 10% for the SID group and 5% for the RF group. Contrary to accepted opinion, the suction-irrigation drainage is an appropriate therapy for deep sternal wound infections. Nevertheless, deep sternal wound infections after cardiac surgery remain severe complications and are related to increased morbidity and mortality.

  3. Lactococcus lactis, A Tool for the Delivery of Therapeutic Proteins Treatment of IBD

    Directory of Open Access Journals (Sweden)

    Lothar Steidler

    2001-01-01

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic intestinal inflammatory diseases that consists of ulcerative colitis (UC, an inflammation of the large intestine, and Crohn�s disease (CD, which can affect any part of the gastrointestinal tract. IBD affects approximately 1 in every 1000 individuals in western countries. There is a marked tendency in the age of onset toward gradually younger people. IBD represents a genuine problem in public health because of the absence of etiologic treatment. The clinical image is characterized by recurrent segmental or total inflammatory involvement of the large and/or small intestine, often resulting in a chronic, unpredictable course. The symptoms of both are extremely unpleasant and impact all aspects of quality of life. They include diarrhea, abdominal pain, rectal bleeding, fever, nausea, weight loss, lethargy, and loss of appetite. If left untreated, malnutrition, dehydration, and anemia follow, which, in extreme cases, can even lead to death. Although many patients are managed successfully with conventional medical therapy, such as anti-inflammatory corticosteroid treatment, some stay refractory to treatment, most will have recurrent activity of disease, and two thirds will require surgery. Administered orally or by injection, only a fraction of the active components of most conventional drugs reaches the intended target site, the inflamed intestinal lining. This is not only an inefficient way to deliver drugs, but, more important, means that patients are often subject to a spectrum of unpleasant side effects that result from the high levels of the drugs in other, otherwise healthy tissues and organs of the body.

  4. The therapeutic potential of escitalopram in the treatment of panic disorder

    Directory of Open Access Journals (Sweden)

    Mark H Townsend

    2007-01-01

    Full Text Available Mark H Townsend, Erich J ConradDepartment of Psychiatry, Louisiana State University Health Sciences Center New Orleans, New Orleans, Louisiana, USAAbstract: Panic disorder is a chronic and disabling condition that is often accompanied by other psychiatric and medical conditions. The serotonin reuptake inhibitors (SSRIs and serotoninnorepinephrine reuptake inhibitors (SNRIs have been used effectively with panic disorder (PD and conditions in which panic attacks frequently occur. Escitalopram is the most selective SSRI and a variety of evidence suggests it is of great value in the treatment of panic disorder. In this paper, we review the theoretical and practical implications of its use.Keywords: panic disorder, escitalopram, antidepressant, serotonin

  5. Therapeutic potential of functional selectivity in the treatment of heart failure

    DEFF Research Database (Denmark)

    Christensen, Gitte Lund; Aplin, Mark; Hansen, Jakob Lerche

    2010-01-01

    Adrenergic and angiotensin receptors are prominent targets in pharmacological alleviation of cardiac remodeling and heart failure, but their use is associated with cardiodepressant side effects. Recent advances in our understanding of seven transmembrane receptor signaling show that it is possible...... to design ligands with "functional selectivity," acting as agonists on certain signaling pathways while antagonizing others. This represents a major pharmaceutical opportunity to separate desired from adverse effects governed by the same receptor. Accordingly, functionally selective ligands are currently...... pursued as next-generation drugs for superior treatment of heart failure....

  6. Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.

    Science.gov (United States)

    Grattagliano, I; Bonfrate, L; Ruggiero, V; Scaccianoce, G; Palasciano, G; Portincasa, P

    2014-01-01

    Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.

  7. Audiological evidence of therapeutic effect of steroid treatment in neuromyelitis optica with hearing loss.

    Science.gov (United States)

    Takanashi, Yoshitaka; Misu, Tatsuro; Oda, Kazuha; Miyazaki, Hiromitsu; Yahata, Izumi; Hidaka, Hiroshi; Fujihara, Kazuo; Kawase, Tetsuaki; Kobayashi, Toshimitsu; Katori, Yukio

    2014-12-01

    Neuromyelitis optica (NMO) is an autoimmune astrocytopathy caused by anti-aquaporin 4 antibody. Only two patients with NMO have been reported presenting with hearing disorders to our knowledge. We recently treated a 40-year-old woman with NMO complaining of right hearing loss. Audiometry showed minimal asymmetry, but the auditory brainstem responses (ABR) were severely attenuated on the right. The attenuated ABR and her aural symptoms (hearing loss and fullness) improved after steroid treatment. The present case shows that the retrocochlear-type hearing loss may be associated with NMO.

  8. Treatment of acquired arteriovenous fistula with severe hemodynamic effects: therapeutic challenge

    Directory of Open Access Journals (Sweden)

    Bruna Ferreira Pilan

    2014-03-01

    Full Text Available A 34-year-old female patient with severe heart failure and pulmonary hypertension was diagnosed late with a high-output acquired arteriovenous fistula between the right common iliac vein and artery. The most probable cause was an iatrogenic vascular injury inflicted during a prior laparoscopic cholecystectomy. Treatment was conducted by placement of an endoprosthesis in the common iliac artery, achieving total exclusion of the fistula and complete remission of symptoms. Considering the options available for treating this type of lesion, endovascular techniques are becoming ever more effective and are now the option of first-choice for management of this pathology.

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

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

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

  10. Degarelix and its therapeutic potential in the treatment of prostate cancer

    Directory of Open Access Journals (Sweden)

    Christian Doehn

    2009-05-01

    Full Text Available Christian Doehn, Martin Sommerauer, Dieter JochamDepartment of Urology, University of Lübeck Medical School, Lübeck, GermanyAbstract: Degarelix is a gonadotropin-releasing hormone (GnRH antagonist for the treatment of patients with prostate cancer in whom hormonal therapy is indicated. Two phase II trials and one phase III have been published as full papers in the literature. In the dose-finding phase II studies an initial dose of 240 mg degarelix sc followed by a monthly injection of 80 mg or 160 mg degarelix sc was sufficient to keep testosterone levels ≤ 0.5 ng/ml. In a phase III trial it was demonstrated that degarelix was not inferior (in terms of testosterone suppression and prostate-specific antigen [PSA] decline compared to standard hormonal therapy, ie, a GnRH agonist such as leuprolide. In fact, degarelix was associated with a faster testosterone suppression and PSA decline than leuprolide. Adverse events such as pain at the injection site (40% vs <1% and chills (4% vs 0% were more commonly associated with degarelix. Also, degarelix is currently only available as one-month depot whereas in daily practice three-month depots (of GnRH agonists are the preferred regimen. However, degarelix was recently approved by the US Food and Drug Administration for the treatment of advanced prostate cancer.Keywords: prostate cancer, hormonal therapy, GnRH antagonist, degarelix, testosterone, flare

  11. The Therapeutic Effectiveness of the Coadministration of Weekly Risedronate and Proton Pump Inhibitor in Osteoporosis Treatment

    Directory of Open Access Journals (Sweden)

    Mizue Tanaka

    2014-01-01

    Full Text Available This trial was conducted to investigate the long-term effects of proton pump inhibitor (PPI coadministration on the efficacy of weekly risedronate treatment for osteoporosis. Ninety-six women over 50 years old with low bone mineral density (BMD participated in this trial. Subjects were randomly divided into 2 groups: a 17.5 mg dose of sodium risedronate was administered weekly, with or without a daily 10 mg dose of sodium rabeprazole (n=49 and 47 in the BP + PPI and BP groups, resp.. The following biomarkers were measured at the baseline and every 3 months: bone-specific alkaline phosphatase, N-terminal telopeptide of type I collagen corrected for creatinine, parathyroid hormone, BMD of the lumbar spine, and physical parameters evaluated according to the SF-36v2 Health Survey. Statistical comparisons of these parameters were performed after 6, 12, 18, and 24 months. The Δ values of improvement in physical functioning after 12 months and bodily pain after 6 and 12 months in the BP + PPI group were significantly larger than those in the BP group. These results suggest that PPI does not adversely affect bone metabolism. Alternatively, approved bone formation by concomitant PPI treatment may have had favorable effects on the improvement of bodily pain and physical functions.

  12. Bibliotherapy: the therapeutic use of didactic and literary texts in treatment, diagnosis, prevention, and training.

    Science.gov (United States)

    Silverberg, Lawrence I

    2003-03-01

    The term bibliotherapy has been defined by Russell and Shrodes as "a process of dynamic interaction between the personality of the reader and literature--an interaction which may be used for personality assessment, adjustment, and growth." In the clinical setting, the dynamics that promote change in a patient-reader can include identification, projection, introjection, catharsis, and insight. Clinicians may use bibliotherapy as a tool for patient treatment, medical diagnosis, and the prevention of illness related to psychosocial dysfunction, allowing for gradual and mutual insight into patient complaints over time. Bibliotherapy may display efficacy on intellectual, psychosocial, interpersonal, emotional, and behavioral levels. The author identifies two basic types of resources that are useful to clinicians administering bibliotherapy: didactic texts, which are instructive, and imaginative literature, which can be a literary text, biography, or autobiography and fosters an imaginative response from the patient-reader. The author identifies the advantages and risks of using bibliotherapy and explores its possible applications in osteopathic medical education, encouraging osteopathic medical educators to familiarize themselves with this treatment modality.

  13. Antisense oligonucleotides as innovative therapeutic strategy in the treatment of high-grade gliomas.

    Science.gov (United States)

    Caruso, Gerardo; Caffo, Mariella; Raudino, Giuseppe; Alafaci, Concetta; Salpietro, Francesco M; Tomasello, Francesco

    2010-01-01

    Despite the intensive recent research in cancer therapy, the prognosis in patients affected by high-grade gliomas is still very unfavorable. The efficacy of classical anti-cancer strategies is seriously limited by lack of specific therapies against malignant cells. The extracellular matrix plays a pivotal role in processes such as differentiation, apoptosis, and migration in both the normal and the pathologic nervous system. Glial tumors seem to be able to create a favorable environment for the invasion of glioma cells in cerebral parenchyma when they combine with the extracellular matrix via cell surface receptors. Glioma cells synthesize matrix proteins, such as tenascin, laminin, fibronectin that facilitate the tumor cell's motility. New treatments have shown to hit the acting molecules in the tumor growth and to increase the efficacy and minimize the toxicity. Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of action of antisense oligonucleotides and report clinical and experimental studies on the treatment of high-grade gliomas. We will also report the patents of preclinical and/or clinical studies that adopt the antisense oligonucleotide therapy list in cerebral gliomas.

  14. Intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: present status and practical therapeutic guidelines.

    Science.gov (United States)

    Dalakas, M C

    1999-11-01

    This review summarizes the current status of intravenous immunoglobulin (IVIg) in the treatment of autoimmune neuromuscular disorders and the possible mechanisms of action of the drug based on work in vivo, in vitro, and in animal models. Supply of idiotypic antibodies, suppression of antibody production, or acceleration of catabolism of immunoglobulin G (IgG) are relevant in explaining the efficacy of IVIg in myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and antibody-mediated neuropathies. Suppression of pathogenic cytokines has putative relevance in inflammatory myopathies and demyelinating neuropathies. Inhibition of complement binding and prevention of membranolytic attack complex (MAC) formation are relevant in dermatomyositis (DM), Guillain-Barré syndrome (GBS), and MG. Modulation of Fc receptors or T-cell function is relevant in chronic inflammatory demyelinating polyneuropathy (CIDP), GBS, and inflammatory myopathies. The clinical efficacy of IVIg, based on controlled clinical trials conducted in patients with GBS, CIDP, multifocal motor neuropathy (MMN), DM, MG, LEMS, paraproteinemic IgM anti-myelin-associated glycoprotein (anti-MAG) demyelinating polyneuropathies, and inclusion body myositis is summarized and practical issues related to each disorder are addressed. The present role of IVIg therapy in other disorders based on small controlled or uncontrolled trials is also summarized. Finally, safety issues, risk factors, adverse reactions, spurious results or serological tests, and practical guidelines associated with the administration of IVIg in the treatment of neuromuscular disorders are presented.

  15. The old and new therapeutic approaches to the treatment of giardiasis: Where are we?

    Directory of Open Access Journals (Sweden)

    Haendel GNO Busatti

    2009-06-01

    Full Text Available Haendel GNO Busatti1, Joseph FG Santos2, Maria A Gomes11Departmento de Parasitologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil; 2Hospital Santa Casa de Misericórdia de Belo Horizonte, Minas Gerais, BrasilAbstract: Giardia lamblia is the causative agent of giardiasis, one of the most common parasitic infections of the human intestinal tract. This disease most frequently affects children causing abdominal pain, nausea, vomiting, acute or chronic diarrhea, and malabsorption syndrome. In undernourished children, giardiasis is a determining factor in retarded physical and mental development. Antigiardial chemotherapy focuses on the trophozoite stage. Metronidazole and other nitroimidazoles have been used for decades as the therapy of choice against giardiasis. In recent years many other drugs have been proposed for the treatment of giardiasis. Therefore, several synthetic and natural substances have been tested in search of new giardicidal compounds. This study is a review of drugs used in in vitro and in vivo tests, and also drugs tested in clinical trials (nonrandomized and randomized.Keywords: Giardia lamblia; treatment; new drugs

  16. Designing Multi-Targeted Therapeutics for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Orhan, Ilkay Erdogan; Senol, F Sezer

    2016-01-01

    Due to multi-faceted pathology of AD; no drug can seize the progress of the disease, whereas only the symptomatic treatment is available at the moment. Several drug classes to treat AD are available in clinical use, AChEIs being the most prescribed. In addition to AChEIs, secretase enzymes and iron chelators have turned out to be the focus of research and the popular targets in drug discovery against AD. The latest approaches such as immunotherapy, multi-targeted drug ligand design, AChE inhibitors, antioxidants, metal chelators, monoamine oxidase (MAO) inhibitors, antiinflammatory drugs, and N-methyl-D-aspartate (NMDA) inhibitors are currently in use to cure this disease to some extent. But, there is a certain need to develop new drugs to fight with AD, particularly acting on multi-targets or with dual mechanisms of action. In this review, a particular emphasis will be focused on multitargets aiming at AD to design new drug molecules with respect to treatment strategies and preventive measures. Since the underlying pathogenesis of AD is complicated and still under investigation, the attempts to design highly selective and potent agents to treat AD are quite intensively continuing. In this respect, designing novel drugs with dual/multi-acting mechanisms seems to be more rational.

  17. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin

    Directory of Open Access Journals (Sweden)

    Seufert J

    2015-11-01

    Full Text Available Jochen SeufertDepartment of Endocrinology and Diabetology, Clinic for Internal Medicine II, Freiburg University Hospital, Freiburg, GermanyAbstract: Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2 inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These "concomitant effects" are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand

  18. Monitoring of high-intensity focused ultrasound treatment by shear wave elastography induced by two-dimensional-array therapeutic transducer

    Science.gov (United States)

    Iwasaki, Ryosuke; Takagi, Ryo; Nagaoka, Ryo; Jimbo, Hayato; Yoshizawa, Shin; Saijo, Yoshifumi; Umemura, Shin-ichiro

    2016-07-01

    Shear wave elastography (SWE) is expected to be a noninvasive monitoring method of high-intensity focused ultrasound (HIFU) treatment. However, conventional SWE techniques encounter difficulty in inducing shear waves with adequate displacements in deep tissue. To observe tissue coagulation at the HIFU focal depth via SWE, in this study, we propose using a two-dimensional-array therapeutic transducer for not only HIFU exposure but also creating shear sources. The results show that the reconstructed shear wave velocity maps detected the coagulated regions as the area of increased propagation velocity even in deep tissue. This suggests that “HIFU-push” shear elastography is a promising solution for the purpose of coagulation monitoring in deep tissue, because push beams irradiated by the HIFU transducer can naturally reach as deep as the tissue to be coagulated by the same transducer.

  19. Amyloid Beta and Tau Proteins as Therapeutic Targets for Alzheimer’s Disease Treatment: Rethinking the Current Strategy

    Directory of Open Access Journals (Sweden)

    Siddhartha Mondragón-Rodríguez

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is defined by the concurrence of accumulation of abnormal aggregates composed of two proteins: Amyloid beta (Aβ and tau, and of cellular changes including neurite degeneration and loss of neurons and cognitive functions. Based on their strong association with disease, genetically and pathologically, it is not surprising that there has been a focus towards developing therapies against the aggregated structures. Unfortunately, current therapies have but mild benefit. With this in mind we will focus on the relationship of synaptic plasticity with Aβ and tau protein and their role as potential targets for the development of therapeutic drugs. Finally, we will provide perspectives in developing a multifactorial strategy for AD treatment.

  20. Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action.

    Science.gov (United States)

    Yamaguchi, Osamu

    2013-01-01

    Recent studies suggest that antimuscarinics might suppress bladder afferent activity by blocking muscarinic receptors in the urothelium, myofibroblasts and detrusor, thereby improving overactive bladder symptoms. β(3)-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β(3)-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β(3)-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β(3)-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β(3)-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α(1)-Adrenoceptor antagonists (α(1)-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α(1)(A) subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α(1)(A)-adrenoceptors are additionally involved in the generation of storage symptoms. The α(1)(D) subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α(1)-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α(1)-blockers and antimuscarinics has been recommended. Treatment with 5α-reductase inhibitor for 1 year improves urinary symptoms and flow rate by reducing prostatic volume in men with benign prostatic enlargement. A pooled analysis showed that the long-term (2 or 4 years) treatment with 5α-reductase inhibitor reduced the rate of progression to acute urinary retention and surgery. Combination therapy with 5α-reductase inhibitor and α(1)-blocker was shown to provide a rapid improvement in lower urinary tract symptoms, and reduce the relative risk of acute urinary retention and benign prostatic hyperplasia

  1. Therapeutic Observation on Treatment of Enuresis with Combined Auricular Pressure and Tuina

    Institute of Scientific and Technical Information of China (English)

    王秋景; 刘玉泉; 王山

    2006-01-01

    Ninety-two cases of enuresis were treated with auricular point pressure onthe kidney (MA-SC), bladder (MA-SC 8), lung (MA-IC 1), heart (MA-IC), liver (MA-SC 5), Er Shenmen(MA-TF 1),Zhen (MA-AT) and Subcortex (MA-AT 1) plus tuina. After treatment, 61 cases were cured, 28 cases were effective and 3 cases were ineffective, with an effective rate of 96.7%.%贴压耳穴肾、膀胱、肺、心、肝、神门、枕和皮质下,结合推拿疗法,治疗了92例遗尿症患者,经治疗后痊愈61例,好转28例,无效3例,有效率96.7%.

  2. Effectiveness of therapeutic physical exercise in the treatment of patellofemoral pain syndrome: a systematic review.

    Science.gov (United States)

    Alba-Martín, Pablo; Gallego-Izquierdo, T; Plaza-Manzano, Gustavo; Romero-Franco, Natalia; Núñez-Nagy, Susana; Pecos-Martín, Daniel

    2015-07-01

    [Purpose] The aim of this study was to analyze the effectiveness of conservative treatment of patellofemoral pain syndrome with physical exercise. [Subjects and Methods] A computer-based review conducted of four databases (PubMed, the Cochrane Library, PEDro, and the University Library) was completed based on the inclusion criteria of patellofemoral pain syndrome patients treated with physical exercise methods and examination with self-reported pain and/or functional questionnaires. [Results] The findings of ten clinical trials of moderate to high quality were evaluated to determine the effectiveness of physical exercise as conservative management for patellofemoral pain syndrome. [Conclusion] The intervention programs that were most effective in relieving pain and improving function in patellofemoral pain syndrome included proprioceptive neuromuscular facilitation stretching and strengthening exercises for the hip external rotator and abductor muscles and knee extensor muscles.

  3. Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: Drug metabolism and its related interactions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice.METHODS: Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006. RESULTS: Seven classes of drugs were chosen, including gastric proton pump inhibitors, histamine H2-receptor antagonists, benzamide-type gastroprokinetic agents, selective 5-HT3 receptor antagonists, fluoroquinolones, macrolide antibiotics and azole antifungals. They showed significant differences in metabolic profile (I.e., the fraction of drug metabolized by cytochrome P450 (CYP), CYP reaction phenotype, impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential). Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues. CONCLUSION: Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy. The relevant CYP knowledge helps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.

  4. Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases.

    Science.gov (United States)

    Harguindey, Salvador; Stanciu, Daniel; Devesa, Jesús; Alfarouk, Khalid; Cardone, Rosa Angela; Polo Orozco, Julian David; Devesa, Pablo; Rauch, Cyril; Orive, Gorka; Anitua, Eduardo; Roger, Sébastien; Reshkin, Stephan J

    2017-04-01

    During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have never been described in any other disease and now appear to be a specific hallmark of malignancy. As a consequence of this intracellular acid-base homeostatic failure, the attempt to induce cellular acidification using proton transport inhibitors and other intracellular acidifiers of different origins is becoming a new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator of apoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing data showing that different ion channels contribute to mediate significant aspects of cancer pH regulation and etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm into the opposite metabolic and homeostatic acid-base situation found in human neurodegenerative diseases (HNDDs), which opens novel concepts in the prevention and treatment of HNDDs through the utilization of a cohort of neural and non-neural derived hormones and human growth factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The Relationship Between Brain Oscillatory Activity and Therapeutic Effectiveness of Transcranial Magnetic Stimulation in the Treatment of Major Depressive Disorder

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    Andrew Francis Leuchter

    2013-02-01

    Full Text Available Major Depressive Disorder (MDD is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive Transcranial Magnetic Stimulation (rTMS is a robust treatment for MDD, but the mechanism of action (MOA of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this mechanism of action and achieve better antidepressant effectiveness. We propose that rTMS can be administered: 1 synchronized to a patient’s individual alpha rhythm (IAF, or synchronized rTMS (sTMS; 2 as a low magnetic field strength sinusoidal wave form; and, 3 broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

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

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    Kreuels Benno

    2008-10-01

    Full Text Available Abstract Background Intermittent preventive treatment in infants (IPTi with sulphadoxine-pyrimethamine (SP reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Methods Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Results Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. Conclusion The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Trial registration Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial and NCT ID # 00167843 (Lambaréné Trial, http://www.clinicaltrials.gov.

  7. Euterpe oleracea Extract (Açaí) Is a Promising Novel Pharmacological Therapeutic Treatment for Experimental Endometriosis

    Science.gov (United States)

    Machado, Daniel Escorsim; Rodrigues-Baptista, Karina Cristina; Alessandra-Perini, Jessica; Soares de Moura, Roberto; dos Santos, Thiago Alves; Pereira, Kariny Gomes; Marinho da Silva, Yasmin; Souza, Pergentino José Cunha; Nasciutti, Luiz Eurico; Perini, Jamila Alessandra

    2016-01-01

    This study investigated the therapeutic potential of Euterpe oleracea extract (açaí) on the growth and survival of endometriotic lesions using an experimental model. Twenty female Sprague-Dawley rats were randomized into two groups after the implantation and establishment of autologous endometrium onto the peritoneum abdominal wall and treated with 200 mg/kg hydroalcoholic solution extract from açaí stone or vehicle via gastric tube for 30 consecutive days. Body weight, lesion surface areas, histological and immunohistochemistry analyses of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and F4-80 were performed. Levels of VEGF, VEGFR-2, MMP-9 and COX-2 mRNA were measured. Flow cytometry of F4-80 was performed, and ELISA immunoassays measured prostaglandin E2 (PGE2), VEGF and nitric oxide (NO) and concentrations. Macrophage cell line J774.G8 was treated with 10, 20, and 40 μg/mL of açaí for 24, 48 and 72 h, and cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Açaí treatment significantly decreased the implant size, and histological examination indicated atrophy and regression. A reduction in immunostaining and mRNA expression of VEGF, MMP-9 and COX-2 was observed, and F4-80 was lower in the treated group than the control group. The treated group also exhibited lower concentrations of PGE2, VEGF and NO compared to the control group. Macrophages cells treated with 20 and 40 μg/ml of açaí reduced cell viability in about 50% after 24, 48 and 72 h. Our results suggest that açaí effectively suppressed the establishment and growth of endometriotic lesions, and this agent is a promising novel pharmacological therapeutic treatment for endometriosis. PMID:27851787

  8. Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.

    Science.gov (United States)

    Tetzlaff, Michael T; Teh, Bin S; Timme, Terry L; Fujita, Tetsuo; Satoh, Takefumi; Tabata, Ken-Ichi; Mai, Wei-Yuan; Vlachaki, Maria T; Amato, Robert J; Kadmon, Dov; Miles, Brian J; Ayala, Gustavo; Wheeler, Thomas M; Aguilar-Cordova, Estuardo; Thompson, Timothy C; Butler, E Brian

    2006-02-01

    The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity.

  9. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    Science.gov (United States)

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. Copyright © 2013 AlphaMed Press.

  10. Rapid Treatment of Leukostasis in Leukemic Mantle Cell Lymphoma Using Therapeutic Leukapheresis: A Case Report

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    Xuan Duc Nguyen

    2011-01-01

    Full Text Available We describe a case of severe leukocytosis caused by leukemic mantle cell lymphoma (MCL, complicated by leukostasis with myocardial infarction in which leukapheresis was used in the initial management. A 73-year-old male presented to the emergency department because of fatigue and thoracic pain. Blood count revealed 630 × 109/L WBC (white blood cells. The electrocardiogram showed ST-elevation with an increase of troponin and creatinine kinase. The diagnosis was ST-elevation myocardial infarction (STEMI induced and complicated by leukostasis. Immunophenotyping, morphology, cytogenetic and fluorescence-in-situ-hybridization analysis revealed the diagnosis of a blastoid variant of MCL. To remove leukocytes rapidly, leukapheresis was performed in the intensive care unit. Based on the differential blood count with 95% blasts, which were assigned to the lymphocyte population by the automatic hematology analyzer, leukapheresis procedures were then performed with the mononuclear cell standard program on the Spectra cell separator. The patient was treated with daily leukapheresis for 3 days. The WBC count decreased to 174 × 109/L after the third leukapheresis, with a 72% reduction. After the second apheresis, treatment with vincristine, cyclophosphamide, and prednisolone was started. The patient fully recovered in the further course of the treatment. To the best of our knowledge, this is the first report on blastoid MCL with leukostasis associated with a STEMI that was successfully treated by leukapheresis. Effective harvest of circulating lymphoma cells by leukapheresis requires adaptation of instrument settings based on the results of the differential blood count prior to apheresis.

  11. Therapeutic potential of TAS-102 in the treatment of gastrointestinal malignancies.

    Science.gov (United States)

    Peters, Godefridus J

    2015-11-01

    Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda®). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2-3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer.

  12. Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features.

    Science.gov (United States)

    Mazza, Alberto; Armigliato, Michela; Marzola, Maria Cristina; Schiavon, Laura; Montemurro, Domenico; Vescovo, Giorgio; Zuin, Marco; Chondrogiannis, Sotirios; Ravenni, Roberta; Opocher, Giuseppe; Colletti, Patrick M; Rubello, Domenico

    2014-04-01

    Pheochromocytoma (PH) and paraganglioma (PG) are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and the sympathetic ganglia, respectively. Although are unusual cause of hypertension (HT) accounting for at most 0.1-0.2 % of cases, they may lead to severe and potentially lethal hypertensive crisis due to the effects of the released catecholamines. However, both PH and PG may be asymptomatic as ~30 % of subjects are normotensive or have orthostatic hypotension and in these cases the 24 h ambulatory blood pressure (BP) monitoring is an important toll to diagnose and treat HT. HT treatment may be difficult when PH or PG occurs in pregnancy or in the elderly subjects and in these cases a multidisciplinary team is required. When surgical excision is mandatory the perioperative management requires the administration of selective α1-adrenergic blocking agents (i.e., doxazosin, prazosin or terazosin) followed by a β-adrenergic blockade (i.e., propranolol, atenolol). This latter should never be started first because blockade of vasodilatory peripheral β-adrenergic receptors with unopposed α-adrenergic receptor stimulation can lead to a further elevation of BP. Although labetalol is traditionally considered the ideal agent due to its α- and β-adrenergic antagonism, experimental studies do not support its use in this clinical setting. As second regimen, the administration of vasodilators as calcium channel blockers (i.e., nicardipine, nifedipine) may be required to control BP. Oral and sublingual short-acting nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. The latest evidences into the diagnosis and treatment of hypertensive crisis due to PH and PG are reviewed here.

  13. Stem cells as therapeutical option for the treatment of bronchopulmonary dysplasia

    Directory of Open Access Journals (Sweden)

    Dominik Monz

    2015-12-01

    Full Text Available During the past decades clinical results in neonatology have improved dramatically and increased the survival rate of preterm infants significantly. However, the short and long term outcome of these high-risk preterm infants is mainly influenced by respiratory diseases and neurological damages. Despite great advances in perinatal medicine, there is still no satisfactory treatment for bronchopulmonary dysplasia (BPD and current approaches are only supportive, have strong adverse effects or only show small benefits. Stem cell based therapies as well as other modes of regenerative strategies are applied as standard therapy in childhood predominantly in paediatric oncology. To date, such therapies have successfully been applied to treat immunodeficiency disorders and aplastic anaemia. But regenerative medicine might be an option for the treatment of BPD in preterm infants. According to some first preclinical results stem cell administration appears as a promising tool to improve the clinical outcome in high-risk infants. For severe neonatal diseases, e.g. hypoxic-ischemic encephalopathy (HIE in term neonates or BPD in preterm infants, a number of animal models have been established. Although these studies showed positive effects of stem cells in animal models of BPD several questions still remain. Further studies with appropriate preclinical neonate models and carefully controlled clinical trials are needed to assess the significance of regenerative therapies. In this review, we summarize recent results of some experimental and clinical studies that used stem cells to treat BPD associated with impairment of lung development. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  14. Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program

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    Melkamu Merid Mengesha

    2016-07-01

    Full Text Available Background: The outpatient therapeutic care program (OTP of children with severe acute malnutrition (SAM has been decentralized to health post level in Ethiopia since 2008–2009. However, there is a lack of evidence regarding treatment outcomes and factors related to the duration of stay on treatment after its decentralization to health post level. Objective: This study was aimed to assess treatment outcome and factors affecting time to recovery in children with SAM treated at OTP. Design: Health facility–based retrospective cohort study was conducted using data from 348 patient cards. The outcome variable was time to recovery. Descriptive analysis was done using percentages for categorical data and mean/median for continuous variables. A robust method of analyzing time to event data, the Cox proportional-hazard regression, was used. All statistical tests in this study are declared significant at p<0.05. Result: 89.1% of children with kwashiorkor and 69.4% of children with marasmus were recovered. Of the total children studied, 22% were readmitted cases. The median time of recovery was 35 days for children with kwashiorkor and 49 days for children with marasmus. Children older than 3 years were 33% less likely to achieve nutritional recovery [adjusted hazard ratio, AHR=0.67, 95% confidence interval, CI (0.46, 0.97]. Similarly, marasmic children stayed longer on treatment [AHR=0.42, 95% CI (0.32, 0.56]. However, children who gained Mid-Upper Arm Circumference (MUAC ≥ 0.24 mm/day were 59% more likely to recover faster [AHR=1.59, 95% CI (1.23, 2.06]. Conclusions: Close monitoring of weight and MUAC gain to assess nutritional improvement with due emphasis given to children with lower admission weight, children of age 3 years and above and marasmic children will have a positive effect on treatment duration and outcome.

  15. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    Science.gov (United States)

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs

  16. Therapeutic Potential of Thalidomide and Its Analogues in the Treatment of Cancer.

    Science.gov (United States)

    Sherbet, Gajanan V

    2015-11-01

    Thalidomide was synthesised and launched several decades ago as a drug against respiratory infections and was administered to pregnant women for relief of morning sickness. The drug was withdrawn when its teratogenic effects came to light. Thalidomide and its analogues suppressed cell proliferation and angiogenesis and controlled invasion and metastasis of tumours in pre-clinical studies. With the recognition of its immunomodulatory and anti-inflammatory, properties, thalidomide may have found a place in the treatment of many forms of cancer and autoimmune conditions. Herein the signalling pathways modulated by thalidomides via the mediation of vascular endothelial growth factor, phosphoinositide-kinase/protein kinase B and nuclear factor kappa B, and mammalian target of rapamycin, which integrates these signalling systems, are discussed. The mode of action of thalidomides and their strategic utility in therapy are evaluated in the context of potential clinical benefits. Notwithstanding the perceived benefits, the side-effects of thalidomides need to be taken into account; they do exert teratogenic effects in animal models, although being effective at lower doses, the drugs seem to show comparatively manageable and reduced toxicity. Combination therapy of thalidomides and modulators of signaling that they influence may further reduce the severity of the side-effects by delivering inhibitory effects at reduced drug dosages. Pre-clinical evaluations of this kind seem warranted.

  17. Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury

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    Su Jing Chan

    2015-03-01

    Full Text Available Hydrogen sulfide (H2S has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS has been implicated as the predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H2S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD together with high substrate concentrations, indicating that H2S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H2S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment.

  18. Protein-nanoparticle conjugates as potential therapeutic agents for the treatment of hyperlipidemia

    Science.gov (United States)

    Maximov, V. D.; Reukov, V. V.; Barry, J. N.; Cochrane, C.; Vertegel, A. A.

    2010-07-01

    Hyperlipidemia, a condition associated with atherosclerosis, can develop because of the lack of low density lipoprotein (LDL) receptors in hepatocytes. Since injected polymeric nanoparticles are quickly taken up by the liver Kupffer cells, we hypothesize that it is possible to enhance LDL delivery to the liver through the use of LDL-absorbing nanoparticles. Here, we demonstrate the feasibility of the proposed approach in vitro. We used biodegradable and biocompatible polylactide nanoparticles (~100 nm in diameter) with covalently attached apolipoprotein B100 antibody to adsorb LDLs at physiologically relevant concentrations. We showed that up to sixfold decreases of LDL levels can be achieved in vitro upon treatment of LDL suspensions (500 mg dl - 1) with anti-apoB100-nanoparticle conjugates. The study of the uptake of the antibody-nanoparticle-LDL complexes by cells was performed using a mouse macrophage cell line (RAW 264.7) as a model for liver Kupffer cells. We found that macrophages can quickly take up antibody-nanoparticle-LDL complexes and digest them within 24 h. No evidence of cytotoxicity was observed for the experimental conditions used in this study.

  19. Remote therapeutic effect of early nerve transposition in treatment of obstetric al brachial plexus palsy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To report a method and remote therape utic effect of early nerve transposition in treatment of obstetrical brachial pl exus palsy.   Methods: From May 1995 to August 1996, 12 patients who had no r ecovery of biceps 3 months after birth were treated with nerve transposition. Ei ght had neuroma at the upper trunk and 4 had rupture or avulsion of the upper tr unk. Mallet test was used to evaluate the results.   Results: The follow-up of 40-52 months showed that excellent and good recovery in functions was found in 75% of the patients and the excellen t rate of phrenic nerve and accessory nerve transposition was 83.3% and 6 6.7% respectively. A complete recovery in shoulder and elbow joint function wa s in 3 patients and Mallet Ⅳ was in 6 patients.   Conclusions: Satisfactory outcome can be obtained by using earl y nerve transposition in treating obstetrical brachial plexus.Paralysis, obstetric; Peripheral nerves; Nerve trans position

  20. Treatment-resistant Lennox-Gastaut syndrome: therapeutic trends, challenges and future directions

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    Ostendorf AP

    2017-04-01

    Full Text Available Adam P Ostendorf,1 Yu-Tze Ng2 1Department of Pediatrics, Neurology Section, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, 2Department of Pediatrics, Baylor College of Medicine, The Children’s Hospital of San Antonio, San Antonio, TX, USA Abstract: Lennox-Gastaut syndrome is a severe, childhood-onset electroclinical syndrome comprised of multiple seizure types, intellectual and behavioral disturbances and characteristic findings on electroencephalogram of slow spike and wave complexes and paroxysmal fast frequency activity. Profound morbidity often accompanies a common and severe seizure type, the drop attack. Seizures often remain refractory, or initial treatment efficacy fades. Few individuals are seizure free despite the development of multiple generations of antiseizure medications over decades and high-level evidence on several choices. Approved medications such as lamotrigine, topiramate, rufinamide, felbamate and clobazam have demonstrated efficacy in reducing seizure burden. Cannabidiol has emerged as a promising investigational therapy with vast social interest yet lacks a standard, approved formulation. Palliative surgical procedures, such as vagal nerve stimulation and corpus callosotomy may provide reduction in total seizures and drop attacks. Emerging evidence suggests that complete callosotomy provides greater improvement in seizures without additional side effects. Etiologies such as dysplasia or hypothalamic hamartoma may be amenable for focal resection and thus offer potential to reverse this devastating epileptic encephalopathy. Keywords: Lennox-Gastaut syndrome, epilepsy, epilepsy surgery, cannabidiol, epileptic encephalopathy

  1. Observation on Therapeutic Results in Tuina Treatment of 56 Cases of Infantile Constipation

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-mei; SU Chun-lan

    2004-01-01

    将56例小儿便秘患者分为胃肠积热型,气机不畅型和气阴两虚型,取大肠、中脘、八卦、七节骨、承山、足三里和迎香,应用小儿推拿手法治疗.痊愈45例,有效9例,无效2例,总有效率96.5%.%After 56 cases of infantile constipation were divided into the pattern of stagnation of heat in the stomach and intestines, pattern of obstruction of qi activity and pattern of deficiency in both qi and yin, the treatments were given by infantile Tuina techniques on the infantile points of Dachang (Extra),Zhongwan (CV 12), Bagua (Extra), Qijiegu (Extra), Chengshan (BL 57), Zusanli (ST 36) and Yingxiang (LI 20). The results showed cure in 45 cases, effectiveness in 9 cases, failure in 2 cases and the total effective rate was 96.5%.

  2. Free fatty acid receptors as therapeutic targets for the treatment of diabetes

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    Atsuhiko eIchimura

    2014-11-01

    Full Text Available Nutrition regulates energy balance; however, dysfunction of energy balance can cause metabolic disorders, such as obesity and diabetes. Fatty acids are an essential energy source and signaling molecules that regulate various cellular processes and physiological functions. Recently, several orphan G protein-coupled receptors were indentified as free fatty acid receptors (FFARs. GPR40/FFAR1 and GPR120/FFAR4 are activated by medium- and/or long-chain fatty acids, whereas GPR41/FFAR3 and GPR43/FFAR2 are activated by short-chain fatty acids. FFARs are regarded as targets for novel drugs to treat metabolic disorders, such as obesity and type 2 diabetes, because recent studies have showed that these receptors are involved in the energy metabolism in various tissues, including adipose, intestinal, and immune tissue. In this review, we summarize physiological roles of the FFARs, provide a comprehensive overview of energy regulation by FFARs, and discuss new prospects for treatment of metabolic disorders.

  3. The safety of anti PD-1 therapeutics for the treatment of melanoma.

    Science.gov (United States)

    Ramelyte, Egle; Schindler, Sabrina A; Dummer, Reinhard

    2017-01-01

    The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered: The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings. Expert opinion: Even though anti-PD-1 therapies are better tolerated than conventional chemo- or other immune-therapies, they still induce a plethora of AEs. Given the mechanism of action, it is supposed that most if not all of them are immune related. Fortunately, the majority are mild and manageable. However, due to the increase in patients' life expectancy, there is a substantial need to understand and prevent severe cutaneous, pulmonary, neurological and other AEs which have major impact on the quality of life. The safety profile after long term use of these medications is still unclear. In addition, non-steroid based immune interventions to control autoimmunity are still to be developed.

  4. Protein-nanoparticle conjugates as potential therapeutic agents for the treatment of hyperlipidemia

    Energy Technology Data Exchange (ETDEWEB)

    Maximov, V D; Reukov, V V; Barry, J N; Vertegel, A A [Department of Bioengineering, Clemson University, Clemson, SC 29631 (United States); Cochrane, C, E-mail: vertege@clemson.edu [South Carolina Governor' s School for Science and Mathematics, Hartsville, SC 29550 (United States)

    2010-07-02

    Hyperlipidemia, a condition associated with atherosclerosis, can develop because of the lack of low density lipoprotein (LDL) receptors in hepatocytes. Since injected polymeric nanoparticles are quickly taken up by the liver Kupffer cells, we hypothesize that it is possible to enhance LDL delivery to the liver through the use of LDL-absorbing nanoparticles. Here, we demonstrate the feasibility of the proposed approach in vitro. We used biodegradable and biocompatible polylactide nanoparticles ({approx}100 nm in diameter) with covalently attached apolipoprotein B100 antibody to adsorb LDLs at physiologically relevant concentrations. We showed that up to sixfold decreases of LDL levels can be achieved in vitro upon treatment of LDL suspensions (500 mg dl{sup -1}) with anti-apoB100-nanoparticle conjugates. The study of the uptake of the antibody-nanoparticle-LDL complexes by cells was performed using a mouse macrophage cell line (RAW 264.7) as a model for liver Kupffer cells. We found that macrophages can quickly take up antibody-nanoparticle-LDL complexes and digest them within 24 h. No evidence of cytotoxicity was observed for the experimental conditions used in this study.

  5. Observation on Therapeutic Effects of Acupuncture and Tuina in Treatment of Sprains and Strains of Minor Joints at Four Extremities

    Institute of Scientific and Technical Information of China (English)

    崔明; 吉健友; 黄国琪

    2009-01-01

    Objective: To observe the clinical therapeutic effects of acupuncture at the bony clefts in combination with tuina therapy in the treatment of sprains and strains of minor joints at the four extremities. Methods: Ninety cases of sprains and strains of minor joints at four extremities [including metacarpophalangeal (metatarsophalangeal)joints] were divided randomly into three groups by the consulting order. Acupuncture group, in which 30 cases were treated by acupuncture at the bony clefts; tuina group, in which 30 cases were treated by tuina therapy; and observation group, in which 30 cases were treated by acupuncture at the bony clefts and tuina therapy. The treatment was given 6 times a week as one course of treatments, and the therapeutic effects were observed after 2 courses of treatments. Results: The cure rates of the observation group, the acupuncture group and the tuina group reached 50.0%, 20.0% and 16.7% respectively, and the total effective rates reached 93.4%, 70.0% and 73.3% respectively. There were statistical significance between the observation group and the acupuncture and tuina groups (P<0.05); while there was not a statistical difference between the acupuncture group and the tuina group. It was indicated that the therapeutic effect of the observation group was better than that of the acupuncture group and the tuina group. Conclusion: Acupuncture at the bony clefts in combination with tuina therapy is quite effective in the treatment of sprains and strains of metacarpophalangeal (metatarsophalangeal) joints.%目的:观察针刺骨缝配合推拿治疗四肢小关节扭挫伤的临床疗效.方法:将90例四肢小关节[包括掌(跖)指(趾)关节]扭挫伤患者按就诊顺序随机分为针刺组30例,采用单纯针刺骨缝治疗;推拿组30例,采用推拿治疗;观察组30例,采用针刺骨缝结合推拿治疗.每星期治疗6次,为1疗程,治疗2个疗程后观察疗效.结果:观察组、针刺组、推拿组的治愈率分别为50.0%

  6. Antibacterial therapeutics for the treatment of chytrid infection in amphibians: Columbus’s egg?

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    Muijsers Mariska

    2012-09-01

    Full Text Available Abstract Background The establishment of safe and effective protocols to treat chytridiomycosis in amphibians is urgently required. In this study, the usefulness of antibacterial agents to clear chytridiomycosis from infected amphibians was evaluated. Results Florfenicol, sulfamethoxazole, sulfadiazine and the combination of trimethoprim and sulfonamides were active in vitro against cultures of five Batrachochytrium dendrobatidis strains containing sporangia and zoospores, with minimum inhibitory concentrations (MIC of 0.5-1.0 μg/ml for florfenicol and 8.0 μg/ml for the sulfonamides. Trimethoprim was not capable of inhibiting growth but, combined with sulfonamides, reduced the time to visible growth inhibition by the sulfonamides. Growth inhibition of B. dendrobatidis was not observed after exposure to clindamycin, doxycycline, enrofloxacin, paromomycin, polymyxin E and tylosin. Cultures of sporangia and zoospores of B. dendrobatidis strains JEL423 and IA042 were killed completely after 14 days of exposure to 100 μg/ml florfenicol or 16 μg/ml trimethoprim combined with 80 μg/ml sulfadiazine. These concentrations were, however, not capable of efficiently killing zoospores within 4 days after exposure as assessed using flow cytometry. Florfenicol concentrations remained stable in a bathing solution during a ten day period. Exposure of Discoglossus scovazzi tadpoles for ten days to 100 μg/ml but not to 10 μg florfenicol /ml water resulted in toxicity. In an in vivo trial, post metamorphic Alytes muletensis, experimentally inoculated with B. dendrobatidis, were treated topically with a solution containing 10 μg/ml of florfenicol during 14 days. Although a significant reduction of the B. dendrobatidis load was obtained, none of the treated animals cleared the infection. Conclusions We thus conclude that, despite marked anti B. dendrobatidis activity in vitro, the florfenicol treatment used is not capable of eliminating B

  7. Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety.

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    Eva M Marco

    Full Text Available Anxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory. Novel pharmacological targets have emerged in the recent years, and attention has focused on the endocannabinoid (eCB system, given the increasing evidence that supports its central role in emotion, coping with stress and anxiety. In the management of anxiety disorders, drug development strategies have left apart the direct activation of type-1 cannabinoid receptors to indirectly enhance eCB signalling through the inhibition of eCB deactivation, that is, the inhibition of the fatty acid amide hydrolase (FAAH enzyme. In the present study, we provide evidence for the anxiolytic-like properties of a novel, potent and selective reversible inhibitor of FAAH, ST4070, orally administered to rodents. ST4070 (3 to 30 mg/kg per os administered to CD1 male mice induced an increase of time spent in the exploration of the open arms of the elevated-plus maze. A partial reduction of anxiety-related behaviour by ST4070 was also obtained in Wistar male rats, which moderately intensified the time spent in the illuminated compartment of the light-dark box. ST4070 clearly inhibited FAAH activity and augmented the levels of two of its substrates, N-arachidonoylethanolamine (anandamide and N-palmitoylethanolamine, in anxiety-relevant brain regions. Altogether, ST4070 offers a promising anxiolytic-like profile in preclinical studies, although further studies are warranted to clearly demonstrate its efficacy in the clinic management of anxiety disorders.

  8. Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment

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    Huayi Suo

    2014-11-01

    Full Text Available The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo on activated carbon-induced constipation in ICR (Institute of Cancer Research mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin, Gas (gastrin, ET (endothelin, SS (somatostatin, AChE (acetylcholinesterase, SP (substance P, VIP (vasoactive intestinal peptide were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus-, LF-Suo (L- and LF-Suo (H-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L, LF-Suo (H or bisacodyl (100 mg/kg, the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05. By the RT-PCR (reverse transcription–polymerase chain reaction and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor, GDNF (glial cell line-derived neurotrophic factor and decreased TRPV1 (transient receptor potential vanilloid 1, NOS (nitric oxide synthase expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity.

  9. The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer.

    Science.gov (United States)

    Krishnan, Aruna V; Swami, Srilatha; Feldman, David

    2012-09-01

    Calcitriol (1,25-dihydroxyvitamin D(3)), the hormonally active form of vitamin D, inhibits the growth of many malignant cells including breast cancer (BCa) cells. The mechanisms of calcitriol anticancer actions include cell cycle arrest, stimulation of apoptosis and inhibition of invasion, metastasis and angiogenesis. In addition we have discovered new pathways of calcitriol action that are especially relevant in inhibiting the growth of estrogen receptor positive (ER+) BCa cells. Calcitriol suppresses COX-2 expression and increases that of 15-PGDH thereby reducing the levels of inflammatory prostaglandins (PGs). Our in vitro and in vivo studies show that calcitriol decreases the expression of aromatase, the enzyme that catalyzes estrogen synthesis selectively in BCa cells and in the mammary adipose tissue surrounding BCa, by a direct repression of aromatase transcription via promoter II as well as an indirect effect due to the reduction in the levels of PGs, which are major stimulator of aromatase transcription through promoter II. Calcitriol down-regulates the expression of ERα and thereby attenuates estrogen signaling in BCa cells including the proliferative stimulus provided by estrogens. Thus the inhibition of estrogen synthesis and signaling by calcitriol and its anti-inflammatory actions will play an important role in inhibiting ER+BCa. We hypothesize that dietary vitamin D would exhibit similar anticancer activity due to the presence of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) in breast cells ensuring conversion of circulating 25-hydroxyvitamin D to calcitriol locally within the breast micro-environment where it can act in a paracrine manner to inhibit BCa growth. Cell culture and in vivo data in mice strongly suggest that calcitriol and dietary vitamin D would play a beneficial role in the prevention and/or treatment of ER+BCa in women.

  10. The Impeding Role of Self-Critical Perfectionism on Therapeutic Alliance During Treatment and Eating Disorder Symptoms at Follow-up in Patients with an Eating Disorder

    Directory of Open Access Journals (Sweden)

    Jolene van der Kaap-Deeder

    2016-04-01

    Full Text Available This study examines the impeding role of self-critical perfectionism at onset of treatment on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder. Participants were 53 female patients with a mean age of 21.1 years treated for an eating disorder in a specialized inpatient treatment unit. Self-critical perfectionism was assessed at admission, therapeutic alliance was assessed during treatment (after three months of treatment, and eating disorder symptoms were assessed at admission, after three months and one year later. Self-critical perfectionism negatively related to treatment alliance with the therapist. Although self-critical perfectionism was not directly predictive of subsequent changes in eating disorder symptoms, it was indirectly related to less reduction in body dissatisfaction through the therapeutic alliance. These results point to the importance of self-critical perfectionism in the therapeutic alliance and in changes in body image problems. Treatment implications are discussed.

  11. [The contingency of the therapeutic effectiveness with the peculiarities of the non-pharmacological treatment of the patients presenting with chronic cholecystitis].

    Science.gov (United States)

    Poddubnaya, O A

    The elaboration of new technologies for the medical rehabilitation of the patients presenting with chronic cholecystitis in combination with chronic opisthorchiasis is a topical problem facing modern clinical gastroenterology. The application of up-to-date non-pharmacological therapeutic modalities, such as ultrahigh-frequency (UHF) therapy concomitantly with group chronophysiotherapy makes it possible to significantly improve the final outcome of the treatment. The results of clinical studies give evidence of the favourable influence of the combined chronorehabilitative treatment including UHF therapy on the characteristics of the functional state of the biliary-hepatic system and of the organism as a whole. The positive dynamics of these characteristics is suggestive of the high (up to 87,5%) therapeutic effectiveness of the proposed treatment. The investigations into the relationship between this effect and the peculiarities of the combined therapeutic modalities have demonstrated their correlation (χ2=104,13; p=0,0001; V-Kramer´s coefficient =0,35) and showed that the use of combined chronorehabilitation including UHF therapy based on the application of phone resonance radiation guarantees (and is a predictor of) high therapeutic effect (percent concordance =95,6%; standard coefficient=2,13; p=0,001) of the treatment of the patients with chronic cholecystitis in combination with chronic opisthorchiasis. The statistical analysis of the results of application of the modern non-pharmacological therapeutic modalities and the chronobiological approach for the purpose of the combined treatment of patients presenting with chronic cholecystitis in combination with opisthorchiasis with the use of contingency table and logit regression, allowed not only to estimate the interdependence and interrelation between the characteristics of interest but also to reveal predictors of therapeutic effectiveness. These findings are of great practical importance since they can be

  12. Quantitative Evaluation of Therapeutic Efficacy of Endovenous Laser Treatment for Distal Varicose Veins by Tc-99m RBC Venography

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Song, Ki Hoon; Sim, Seung Joo; Kim, Ki Ho [College of Medicine, Univ. of Donga, Busan (Korea, Republic of)

    2003-07-01

    Endovenous laser treatment (EVLT) has been shown to be effective for elimination of greater saphenous (GSV) incompetence. While the result of GSV closure has been studied in detail, the effects in distal GSV and its tributaries following EVLT are still not completely understood. In addition, the optimal time for treatment of remaining varicose veins is not established. We evaluated the clinical and radiological changes of distal varicose veins after EVLT and determined the optimal time for additional treatment of distal varicose veins following EVLT by Tc-99m RBC. Forty GSV (30 patients) were treated with 940 nm or 810 nm diode laser at usual energy setting. Clinical and Duplex evaluation were performed at I week, and at various monthly intervals (2-6 months) following the initial treatment. Tc-99m venography was performed as usual protocol at I month and at every 3 months after EVLT. The distal varicose veins were quantified by determining the ratio of mean counts per pixel in the target and background areas and then comparing the pre-EVLT and post-EVLT values. Thirty-eight (95.0%) GSV were closed following EVLT and remained closed at 1-21 months follow-up examination. The reduction rate of distal varicose veins measured by Tc-99m venography was 22.8% at l month, 42.7% at 3 months, 61.5% at 6 months, and 72.4% at 9 months after EVLT. Fifteen legs (37.5%) required additional phlebectomy at 1 to 3 months after EVLT, while the others (62.5%) showed spontaneous regression of distal veins from one month during follow-up period. Therapeutic efficacy of EVLT for distal varicose vein can be well-evaluated quantitatively by Tc-99m RBC venography. Theses results suggest that after EVLT for GSV, the 'wait' policy would be necessary, rather than the 'wasting' of distal veins concurrently with EVLT.

  13. Observation on the therapeutic effect of aspirin in combined with ozagrel sodium in the treatment of acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Hong-Jing Shen; Hai-Yan He; Ming-Xuan Dai

    2017-01-01

    Objective:To explore the clinical efficacy of aspirin in combined with ozagrel sodium in the treatment of acute cerebral infarction (ACI).Methods:A total of 120 patients with ACI who were admitted in our hospital from May, 2015 to May, 2016 were included in the study and randomized into the study group and the control group with 60 cases in each group. The patients in the two groups were given cerebral edema alleviating, brain cell protecting, cerebral circulation improving, and blood pressure controlling. The patients in the study group were given aspirin enteric-coated tablets, 0.1 g/time, 1 time/d. On the above basis, the patients in the study group were given ozagrel sodium (80 mg) + 0.9% NaCl (250 mL), ivdrip, 2 times/d. The patients in the two groups were treated for 14 d. The venous blood was extracted 1 d after admission and 14 d after treatment. The full automatic biochemical analyzer was used to detect PLT, PT, TT, FIB, and APTT. The radioimmunoassay was used to detect TXB2 and 6-K-PGF1α. The color Doppler ultrasound was used to detect IMT.Results: PLT, PT, TT, and APTT after treatment were not significantly different from those before treatment (P>0.05), but FIB was significantly reduced, and the reduced degree in the study group was significantly superior to that in the control group (P<0.05). After treatment, TXB2 level in the two groups was reduced, while 6-K-PGF1α was elevated, and those in the study group were significantly superior to those in the control group (P<0.05). After treatment, IMT in the two groups was reduced, and the reduced degree in the study group was significantly superior to that in the control group (P<0.05).Conclusions:Aspirin in combined with ozagrel sodium in the treatment of ACI can effectively inhibit the platelet aggregation, improve the coagulation function and cerebral blood supply, promote the recovery of cerebral nerve function after infarction, and enhance the therapeutic effect; therefore, it deserves to be widely

  14. Therapeutic comparison between radiofrequency ablation and percutaneous ethanol injection in treatment of primary liver cancer: a meta-analysis

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    YIN Yu

    2015-06-01

    Full Text Available ObjectiveTo compare the efficacy of radiofrequency ablation (RFA versus percutaneous ethanol injection (PEI in the treatment of primary liver cancer(PLC. MethodsA search of PubMed, EMBASE, CKNI, VIP, and Wanfang Data identified all randomized controlled trials (RCTs related to therapeutic comparison between RFA and PEI in patients with PLC. Quality of each study was assessed, meta-analysis was performed with Review Manager 5.0 software, and the results were analyzed with fixed effect model and random effect model. ResultsSeven RCTs were included in this study. The results of meta-analysis indicated that, compared with the PEI group, the RFA group had a significantly higher tumor necrosis rate (P=0.008, OR=2.66, 95%CI: 1.29-5.48. The 1-, 2-, and 3-year survival rates and 1- and 3-year tumor-free survival rates of the RFA group were significantly higher than those of the PEI group (P<005. The RFA group had significantly lower 1-, 2-, and 3-year local recurrence rates in comparison with the PEI group (P<005. There was no significant difference in 2-year tumor-free survival rate between the two groups (P=0.06. ConclusionThe efficacy of RFA is superior to that of PEI, which is of clinical significance to guide the selection of methods for PLC treatment.

  15. Refractory ascites in systemic lupus erythematosus: further biological support of intraperitoneal steroid treatment as a suitable therapeutical option.

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    Atisha-Fregoso, Yemil; Hernández-Ramírez, Diego F; Olivares-Martínez, Elizabeth; Núñez-Alvarez, Carlos A; Llorente, Luis; Hernández-Molina, Gabriela

    2017-03-01

    The objective of this report was to evaluate the ascitic fluid of a patient with refractory lupus ascites (proband) at different time points-pre- and post-intraperitoneal treatment with dexamethasone-using a multiparametric approach which included the presence of autoantibodies and pro- and anti-inflammatory cytokines and chemokines, and a proteomic analysis. As controls, we studied two additional patients also with lupus ascites (only at basal evaluation) and two patients with ascites due to alcoholic liver cirrhosis. High levels of anti-dsDNA and anti-nucleosomes autoantibodies were detected in the ascitic fluid of all lupus patients and remained elevated in the proband throughout the follow-up. All lupus patients have detectable ascitic high levels of IL-6, IL-8, IL-10, TNF-α, MCP-1, and IGF-1 which diminished gradually in the proband after intraperitoneal dexamethasone. In the proteomic analysis of the ascitic fluid, a marked increment of apolipoprotein A1 was observed and again, it diminished gradually after intraperitoneal treatment. Our findings further support the use of intraperitoneal steroids as an effective therapeutic option for refractory ascites in systemic lupus erythematosus.

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

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    Maercker Andreas

    2007-04-01

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

  17. Therapeutic evaluation of prolonged infusions of β-lactam antibiotics in the treatment and management of critically ill patients

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    Jorge S. Amador

    2017-04-01

    Full Text Available Context: Critically ill patients has a large number of pathophysiological changes product of commitment and organ systems. Therefore, knowledge of the pharmacological properties of antimicrobials is essential to choose the best treatment. In order to optimize the response of antibiotic therapy and these drugs, new strategies have been proposed dosage, the most used drug application of the model, called: Pharmacokinetics/Pharmacodynamics (PK/PD. In the case of β-lactam antibiotics, the PK/PD model is known as time-dependent on the Minimum Inhibitory Concentration (Time > MIC. For optimal concentrations in β-lactam antibiotics, prolonged or continuous infusions, thus exposing the drug on the pathogen is achieved in a longer optimal concentrations through are used. Aims: To evaluate the therapeutic response of β-lactam antibiotics in critically ill patients with prolonged infusions by applying the model PK/ PD. Methods: Prospective observational study (concurrent cohort, taking as a control non-concurrent historic cohort, conducted for a period of seven months in the intensive care unit of the Hospital Clínico San Borja Arriarán (HCSBA, Santiago, Chile. Results: It was found a significant difference in number of days of hospitalization in ICU for the group bolus versus infusion group (12.5 ± 5.4 vs. 18 ± 9.7 days, IC: 1.5-9.5; p = 0.009. Conclusions: This study suggests that there would be a therapeutic advantage in the use of prolonged infusion in ICU stay duration.

  18. Cell therapy: a safe and efficacious therapeutic treatment for Alzheimer's disease in APP+PS1 mice.

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    Nabar, Neel R; Yuan, Fang; Lin, Xiaoyang; Wang, Li; Bai, Ge; Mayl, Jonathan; Li, Yaqiong; Zhou, Shu-Feng; Wang, Jinhuan; Cai, Jianfeng; Cao, Chuanhai

    2012-01-01

    Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2 × Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP + PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future.

  19. Cell therapy: a safe and efficacious therapeutic treatment for Alzheimer's disease in APP+PS1 mice.

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    Neel R Nabar

    Full Text Available Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD. In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2 × Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP + PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future.

  20. Characteristics and outcomes of initial virologic suppressors during analytic treatment interruption in a therapeutic HIV-1 gag vaccine trial.

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    Jonathan Z Li

    Full Text Available BACKGROUND: In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 gag vaccine. OBJECTIVE: To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 log(10 copies/ml during the analytic treatment interruption (ATI and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution. METHODS: HIV-1 gag and pol RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests. RESULTS: Eleven out of 104 participants (10.6% were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04. However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log(10 copies/ml. HIV-1 Gag-specific CD4+ interferon-γ responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-α+ cells expressing either CTLA-4 or PD-1. CONCLUSIONS: Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other

  1. Therapeutic inertia in patients treated with two or more antidiabetics in primary care: Factors predicting intensification of treatment.

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    Mata-Cases, Manel; Franch-Nadal, Josep; Real, Jordi; Gratacòs, Mònica; López-Simarro, Flora; Khunti, Kamlesh; Mauricio, Dídac

    2017-06-28

    To determine the patterns and predictors of treatment intensification in patients with type 2 diabetes on ≥2 non-insulin antidiabetic drugs (NIADs) and inadequate glycaemic control in primary care in Catalonia, Spain. This was a retrospective analysis using electronic medical records from patients with HbA1c ≥ 7% and a first prescription for a new NIAD or insulin recorded from January 2010 to December 2014. Therapeutic inertia was defined as no intensification if HbA1c was ≥8% at baseline or during follow-up. Time to first intensification was evaluated by time-to-event analysis, and factors predicting intensification through a competing-risk regression model. Among 23 678 patients with HbA1c ≥ 7%, 26.2% were censored without treatment intensification after a median follow up of 4.2 years. Among the 12 730 patients in the subgroup with HbA1c ≥ 8% at baseline or during follow-up, therapeutic inertia was present in 18.1% of cases. In the overall cohort, mean HbA1c at initiation of insulin and NIAD were 9.4% ± 1.5% and 8.7% ± 1.3%, respectively. Median time to first intensification was 17.1 months in patients with HbA1c 8.0% to 9.9%, and 10.1 months in those with HbA1c > 10%. Variables strongly associated with intensification were HbA1c values 8.0% to 9.9% (subhazard ratio [SHR], 1.7; 95% CI, 1.65-1.78) and >10% (SHR, 2.5; 95% CI, 2.37-2.68); diabetes duration ≥20 years (SHR, 1.25; 95% CI, 1.11-1.41) and, to a lesser extent, female gender, presence of comorbidities, chronic kidney disease and microvascular complications. Intensification was not undertaken in 1 in 5 patients. Both HbA1c thresholds and time until therapy intensification exceeded current recommendations. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  2. Disfagia aguda de causa oncológica: Manejo terapéutico Acute dysphagia of oncological origin: Therapeutic treatment

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    F. Arias

    2004-01-01

    Full Text Available La disfagia es uno de los síntomas más frecuentes en los pacientes con tumores de cabeza y cuello, y esófago. Éste puede ser el síntoma inicial o, más frecuentemente, relacionado con el tratamiento oncológico. Se revisan los aspectos fisiopatológicos y terapéuticos más importantes de la disfagia aguda de causa oncológica. La deglución es un proceso complejo en el que intervienen numerosas estructuras músculo-esqueléticas bajo el control neurológico de diversos pares craneales. La compleja coordinación neuromuscular necesaria para una correcta deglución puede verse afectada por numerosas situaciones tanto por efecto de los tumores como de su tratamiento, fundamentalmente la cirugía o la radioterapia. En conclusión, se puede afirmar que para un adecuado tratamiento de la disfagia oncológica, es preciso una correcta evaluación inicial y un tratamiento activo, ya que del control de la disfagia, depende no sólo la calidad de vida del paciente, sino en numerosas ocasiones la posibilidad de continuar el tratamiento y por tanto de mantener las posibilidades de curación.Dysphagia is one of the most frequent syndromes in patients with tumours of the head and neck, and the oesophagus. This can be the initial symptom or, more frequently, related to the oncological treatment. We review the most important therapeutic and physio-pathological aspects of acute dysphagia of oncological origin. Deglutition is a complex process in which numerous muscular-skeletal structures intervene under the neurological control of different cranial nerves. The complex neuro-muscular coordination needed for a correct deglutition can be affected by numerous situations, both from the effect of the tumours and from their treatment, basically surgery or radiotherapy. In conclusion, it can be affirmed that for a suitable treatment of oncological dysphagia, a correct initial evaluation and an active treatment are required, since not only the patient’s quality

  3. Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma

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    Babu R

    2012-09-01

    Full Text Available Ranjith Babu, D Cory AdamsonDivision of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USAAbstract: Glioblastoma multiforme (GBM is the most common primary brain tumor in adults and is universally fatal. Despite surgical resection, radiotherapy, and systemic chemotherapy, the median overall survival is less than 15 months. As current therapies are not tumor-specific, treatment commonly results in toxicity. The epidermal growth factor receptor variant III (EGFRvIII is a naturally occurring mutant of EGFR and is expressed on approximately 20% to 30% of GBMs. As it is not expressed on normal cells, it is an ideal therapeutic target. Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. Phase I and II clinical trials have demonstrated significantly higher progression-free and overall survival times in vaccinated patients with EGFRvIII-expressing GBM tumors. Side effects are minimal and mainly consist of hypersensitivity reactions. Due to the efficacy and safety of rindopepimut, it is a promising therapy for patients with GBM. Currently, rindopepimut is undergoing clinical testing in an international Phase III trial for newly diagnosed GBM and a Phase II trial for relapsed GBM.Keywords: CDX-110, EGFRvIII, glioblastoma, immunotherapy, PEPvIII

  4. Therapeutic paint of cidofovir/sucralfate gel combination topically administered by spraying for treatment of orf virus infections.

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    Sonvico, Fabio; Colombo, Gaia; Gallina, Laura; Bortolotti, Fabrizio; Rossi, Alessandra; McInnes, Colin J; Massimo, Gina; Colombo, Paolo; Scagliarini, Alessandra

    2009-06-01

    The aim of the research was to study a new cidofovir/sucralfate drug product to be used as a spray for treating the mucosal and/or skin lesions. The product, i.e., a water suspension of sucralfate (15% w/w) and cidofovir (1% w/w), combines the potent antiviral activity of the acyclic nucleoside phosphonate cidofovir ((S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) and the wound healing properties of sucralfate gel (sucrose octasulphate basic aluminum salt). The product was characterized in vitro with respect to compatibility between drug and carrier, spray particle size, spray deposition, drying kinetics, and drug content and release. An interaction between the two active substances was found. The interaction between sucralfate and cidofovir was counteracted by introducing sodium dihydrogen phosphate (16% w/w) in the preparation. The spray formulation containing cidofovir/sucralfate gel painted the skin and dried quickly to a scab, remaining firmly adhered to the lesions. The therapeutic paint was tested in vivo on lambs infected with orf virus by treating the animals with different cidofovir/sucralfate formulations (0.5% or 1% cidofovir + sucralfate 15% + NaH(2)PO(4) 16% w/w) and with sucralfate gel suspension alone as control. The treatment with formulations containing cidofovir and phosphate salt for four consecutive days resulted in a rapid resolution of the lesions, with scabs containing significantly lower amounts of viable virus when compared with untreated lesions and lesions treated with sucralfate suspension alone.

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

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

    2012-10-22

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

  6. CLINICAL OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE OF JIAJI (EX-B 2) IN THE TREATMENT OF APOPLECTIC SPASTIC HEMIPLEGIA

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jun; TAN Yuan-sheng; LIANG Yun-wu; CHEN Gui-long; WANG Ze-tao

    2005-01-01

    Objective:To compare the therapeutic effects of acupuncture of different acupoints in the treatment of spastic hemiplegia of apoplexy. Methods: Eighty stroke patients with spastic hemiplegia were evenly randomized into control group and treatment group. Forty cases of treatment group were given with acupuncture of Jiaji (夹脊 EX-B2) from T1 to L5, while forty cases of control group were treated with conventional acupoints as Jianyu (肩NFDA1 LI 15), Quchi (曲池 LI 11), Huantiao (环跳 GB 30), Zusanli (足三里 ST 36), Kunlun (昆仑 BL 60), etc. On the diseased side, once daily, with 10 sessions being one therapeutic course, and 3 courses all together. The modified Ashworth Scale (MAS) and neurological deficit grading scale (NDS) were used as the indexes to assess the therapeutic effects. Results: After treatment, the scores of NDS of both treatment and control groups reduced and the difference value between post- and pre-treatment of treatment group was significantly bigger than that of control group. MAS showed a similar tendency in both groups. Of the 40 cases in treatment and control groups, 6 and 1 were cured, 20 and 15 had marked improvement, 9 and 11 had improvement, 4 and 8 failed, 1 and 5 got worse, with the total effective rates being 87.5% and 67.5% respectively. The therapeutic effect of treatment group was significantly superior to that of control group (P<0.01). Conclusion: Acupuncture of Jiaji (EX-B2) is superior to acupuncture of conventional acupoints in alleviating the state of spastic hemiplegia of apoplexy.

  7. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

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    Shohei Ogata

    Full Text Available OBJECTIVES: Although intravenous immunoglobulin (IVIG is highly effective in Kawasaki disease (KD, mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I, the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. METHODS: We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (sST6Gal-I levels were measured by ELISA. RESULTS: There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively. CONCLUSIONS: Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

  8. Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Enfranze, north-west Ethiopia.

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    Getnet, Gebeyaw; Fola, Abebe Alemu; Alemu, Agersew; Getie, Sisay; Fuehrer, Hans-Peter; Noedl, Harald

    2015-06-24

    Plasmodium falciparum accounts for approximately 60% of malaria cases in Ethiopia and artemether-lumefantrine has been used as a first-line treatment for uncomplicated P. falciparum malaria since 2004. The aim of this study was to assess the therapeutic efficacy of artemether-lumefantrine (AL) for the treatment of uncomplicated P. falciparum malaria in north-western Ethiopia. A 28-day one-arm, prospective evaluation of the clinical and parasitological response to the first-line treatment for uncomplicated P. falciparum malaria was conducted in Enfranze Health Centre in accordance with the 2009 WHO efficacy study guidelines. Patients were treated with a 3-day course of AL and clinical and parasitological parameters were monitored over a 28-day follow-up. All data from recruited patients were imported into an electronic data base and Kaplan-Meier survival analysis was used for analysing primary [early treatment failures (ETF), late clinical failure (LCF), late parasitological failures (LPF), and adequate clinical and parasitological response (ACPR)] and secondary (PCT, GCT and FCT) outcomes. Eighty patients were enrolled and all of them completed the 28-day follow-up period. The PCR-corrected cure rate was 95.0% (95% CI 87.0-98.4%) and there were two ETF, one LCF and three LPF. Two of the LPF were classified as re infections by PCR. Seventy three point seven five percent, 91.25 and 95% of patients had cleared their parasitaemia by days 1, 2, and 3, respectively, and 75, 91.25 and 96.25% of patients had cleared their fever by days 1, 2, and 3. All patients completely cleared their gametocytes by day 7. The relatively high cure rate, low proportion of patients still positive on day 3 as well as parasite clearance times in this study would indicate no imminent threat of artemisinin resistance development in the region. However, the threat of spreading or de novo development of artemisinin resistance warrants regular monitoring of drug efficacy throughout the region.

  9. EVALUATION OF THERAPEUTIC EFFICIENCY OF TOPICAL CLOTRIMAZOLE AND TOPICAL MICONAZOLE IN THE TREATMENT OF OTOMYCOSIS- A PROSPECTIVE STUDY

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    Channabasawaraj B Nandyal

    2015-06-01

    Full Text Available Background: Otomycosis a Superficial Fungal Infection of the External auditory canal causes lot of misery to the Patient with tendency of recurrence. Many Antifungals are used for treatment with different percentage of success; still a standard regime is not firmly established. So this study is undertaken to evaluate Therapeutic efficiency of Topical Clotrimazole and Miconazole in treating Otomycosis. Materials and Methods: Present study was conducted on 156 clinically diagnosed cases of Otomycosis. Ear discharge was collected. Identification of fungi was done by standard protocol. Out of 156 cases 135 cases produced positive fungal isolates which were taken for further studies. Cases underwent thorough cleaning in Infected Ear. 1% Clotrimazole Ear drop was used in 70 cases and 1% Miconazole in 65 cases for 1 week and followed up for 1 week to 2 months for clearance or recurrence. Results: Clotrimazole showed good response Symptomatically and Mycological clearance within one week in 66 cases. Persistence of disease to 2-4 weeks in 4 cases and no recurrence within 2 months of follow up with minimal side effects, Where as Miconazole showed good response within one week in 54 cases, 9 cases had persistence of disease to 2-4 weeks and 2 cases had recurrence, burning sensation in 9 patients and 1 case developed allergy and discontinued treatment. Conclusion: Topical Clotrimazole is more Effective, Safe and well tolerated with better Symptomatic relief, Mycological clearance and low relapse rate compared to Topical Miconazole. [Natl J Med Res 2015; 5(2.000: 145-149

  10. Early treatment with addition of low dose prednisolone to methotrexate improves therapeutic outcome in severe psoriatic arthritis

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    Vikram K Mahajan

    2013-01-01

    Full Text Available Psoriatic arthritis (PsA is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs, the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week, given for 4 weeks. Addition of prednisolone (10 mg on alternate days controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week and prednisolone (2.5 mg on alternate days every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than ′steroid rescue′ later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy.

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

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

    2015-02-10

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

  12. Thalidomide Effects in Patients with Hereditary Hemorrhagic Telangiectasia During Therapeutic Treatment and in Fli-EGFP Transgenic Zebrafish Model

    Institute of Scientific and Technical Information of China (English)

    Hong-Ling Peng; Yi-Fang Yi; Shun-Ke Zhou; Si-Si Xie; Guang-Sen Zhang

    2015-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis,mucocutaneous telangiectasia, and arteriovenous malformations.The efficacy of traditional treatments for HHT is very limited.The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.Methods: HHT was diagnosed according to Shovlin criteria.Five HHT patients were treated with thalidomide (100 mg/d).The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide.The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis.Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.Results: The average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P =0.009).The "telangiectatic spot" on the tongue almost vanished;CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation.The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy.The plasma VEGF protein expression was down-regulated in HHT patients.Conclusions: Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients.It also leads to vascular remodeling in the zebrafish model.

  13. Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer.

    Science.gov (United States)

    Ihnen, Maike; zu Eulenburg, Christine; Kolarova, Teodora; Qi, Jing Wei; Manivong, Kanthinh; Chalukya, Meenal; Dering, Judy; Anderson, Lee; Ginther, Charles; Meuter, Alexandra; Winterhoff, Boris; Jones, Siân; Velculescu, Victor E; Venkatesan, Natarajan; Rong, Hong-Mei; Dandekar, Sugandha; Udar, Nitin; Jänicke, Fritz; Los, Gerrit; Slamon, Dennis J; Konecny, Gottfried E

    2013-06-01

    Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. We studied the growth inhibitory effects of rucaparib in a panel of 39 ovarian cancer cell lines that were each characterized for mutation and methylation status of BRCA1/2, baseline gene expression signatures, copy number variations of selected genes, PTEN status, and sensitivity to platinum-based chemotherapy. To study interactions with chemotherapy, we used multiple drug effect analyses and assessed apoptosis, DNA fragmentation, and γH2AX formation. Concentration-dependent antiproliferative effects of rucaparib were seen in 26 of 39 (67%) cell lines and were not restricted to cell lines with BRCA1/2 mutations. Low expression of other genes involved in homologous repair (e.g., BCCIP, BRCC3, ATM, RAD51L1), amplification of AURKA or EMSY, and response to platinum-based chemotherapy was associated with sensitivity to rucaparib. Drug interactions with rucaparib were synergistic for topotecan, synergistic, or additive for carboplatin, doxorubicin or paclitaxel, and additive for gemcitabine. Synergy was most pronounced when rucaparib was combined with topotecan, which resulted in enhanced apoptosis, DNA fragmentation, and γH2AX formation. Importantly, rucaparib potentiated chemotherapy independent of its activity as a single agent. PARP inhibition may be a useful therapeutic strategy for a wider range of ovarian cancers bearing deficiencies in the homologous recombination pathway other than just BRCA1/2 mutations. These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer. ©2013 AACR

  14. Relationship Between Time in Therapeutic Range and Comparative Treatment Effect of Rivaroxaban and Warfarin: Results From the ROCKET AF Trial

    Science.gov (United States)

    Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Harrell, Frank E.; Singer, Daniel E.; Becker, Richard C.; Breithardt, Günter; Halperin, Jonathan L.; Hankey, Graeme J.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Background Time in therapeutic range (TTR) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (cTTR) since such analysis preserves randomized comparisons. Methods and Results TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio (INR) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INRs were performed via standardized finger‐stick point‐of‐care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non‐central nervous system embolism) was examined by quartiles of cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower‐risk patients as reflected by lower CHADS2 scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of cTTRs (P value for interaction=0.71). The hazard of major and non‐major clinically relevant bleeding increased with cTTR (P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold cTTR values. Conclusions The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR. PMID:24755148

  15. Effect of a Mind-Body Therapeutic Program for Infertile Women Repeating In Vitro Fertilization Treatment on Uncertainty, Anxiety, and Implantation Rate

    Directory of Open Access Journals (Sweden)

    Miok Kim, PhD

    2014-03-01

    Conclusion: This study is meaningful as the first intervention program for alleviating uncertainty and anxiety provided during the IVF treatment process. The positive effects of the mind-body therapeutic program in alleviating both uncertainty and anxiety have direct meaning for clinical applications.

  16. The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

    Institute of Scientific and Technical Information of China (English)

    蓝孝筑; 姜玉华

    2003-01-01

    @@ 47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.

  17. A 9-month follow-up of a 3-month web-based alcohol treatment program using intensive asynchronous therapeutic support.

    NARCIS (Netherlands)

    Postel, Marloes Gerda; ter Huurne, E.D.; de Haan, H.A.; van der Palen, Jacobus Adrianus Maria; de Jong, Cor A.J.

    2015-01-01

    Background: Web-based alcohol interventions have demonstrated efficacy in randomized controlled trials. However, most studies have involved self-help interventions without therapeutic support. Objectives: To examine the results of a 3-month web-based alcohol treatment program using intensive,

  18. A 9-month follow-up of a 3-month web-based alcohol treatment program using intensive asynchronous therapeutic support

    NARCIS (Netherlands)

    Postel, M.G.; Huurne, E.D. ter; Haan, H.A. de; Palen, J.A.M. van der; Jong, C.A.J. de

    2015-01-01

    Background: Web-based alcohol interventions have demonstrated efficacy in randomized controlled trials. However, most studies have involved self-help interventions without therapeutic support. Objectives: To examine the results of a 3-month web-based alcohol treatment program using intensive,

  19. Treatment Differences in the Therapeutic Relationship and Introject during a 2-Year Randomized Controlled Trial of Dialectical Behavior Therapy versus Nonbehavioral Psychotherapy Experts for Borderline Personality Disorder

    Science.gov (United States)

    Bedics, Jamie D.; Atkins, David C.; Comtois, Katherine A.; Linehan, Marsha M.

    2012-01-01

    Objective: The present study explored the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. Method: Women meeting "DSM-IV" criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community…

  20. A 9-month follow-up of a 3-month web-based alcohol treatment program using intensive asynchronous therapeutic support.

    NARCIS (Netherlands)

    Postel, M.G.; Huurne, ter E.D.; Haan, de H.A.; Palen, van der Job; Jong, de Cor A.J.

    2015-01-01

    Background: Web-based alcohol interventions have demonstrated efficacy in randomized controlled trials. However, most studies have involved self-help interventions without therapeutic support. Objectives: To examine the results of a 3-month web-based alcohol treatment program using intensive, asynch

  1. Therapeutic hypothermia after cardiac arrest in Long QT syndrome: Could it be an adjunctive treatment to prevent dysrhythmias?

    Directory of Open Access Journals (Sweden)

    Kumar Jatti

    2015-06-01

    Full Text Available Therapeutic hypothermia has been used for neuroprotection following cardiac arrest presenting with ventricular tachycardia or ventricular fibrillation regardless of underlying cause. Long QT syndrome is a cause for polymorphic ventricular tachycardia, and we know that therapeutic hypothermia increases the QT interval. We managed a 27-year-old woman, who was 10 weeks post-partum, who collapsed secondary to ventricular fibrillation at home. Bystander cardiopulmonary resuscitation was started with successful resuscitation after a rescue shock from paramedics. On hospital admission, her computerised tomography head, computerised tomography pulmonary angiogram and echocardiography did not show any abnormality. Her baseline electrocardiogram showed prolonged QTc interval of 504 ms without ischaemic changes. After intubation and ventilation, she was treated with therapeutic hypothermia for 48 h. She had a further episode of polymorphic ventricular tachycardia requiring rescue shock just prior to starting therapeutic hypothermia in hospital. No dysrhythmias occurred during therapeutic hypothermia, although the QTc further increased. After stopping the therapeutic hypothermia, she had two further ventricular tachycardia episodes. After commencement of beta blockers, she remained free of arrhythmias, and an implantable cardioverter defibrillator was implanted, she has recovered without any neurological deficit. Ventricular dysrhythmias caused by prolongation of the QT interval during or after therapeutic hypothermia are not well understood. There has been a report of a patient also having ventricular dysrhythmia 2 h after re-warming post therapeutic hypothermia and also a report of arrhythmia free period during therapeutic hypothermia in a long QT syndrome patient; both these features are present in our patient. Re-warming is not usually known to cause any arrhythmias; however, it could be a problem in those with long QT syndrome. Whether

  2. Differences in effectiveness of intensive programs of treatment for neurotic and personality disorders. Is it worth to monitor the effectiveness of the therapeutic team?

    Directory of Open Access Journals (Sweden)

    Styła, Rafał

    2014-02-01

    Full Text Available Objectives. To test whether three different intensive programs of treatment for neurotic and personality disorders are effective in decreasing neurotic symptoms and traits of neurotic personality and whether there are differences between them in clinical outcome. Method: The sample consisted of 105 patients (83% female, mean age 35 diagnosed with neurosis and personality disorders that were treated in three therapeutic wards under routine inpatient conditions. The therapeutic programs are designed for patients with neurotic and personality disorders. They consist of 6-12 weeks of approximately 5 hours of eclectic group treatment (group psychotherapy, psychodrama, psychoeducation etc.. Participants filled in Symptoms’ Questionnaire KS-II, and Neurotic Personality Questionnaire KON-2006 at the beginning and at the end of the course of psychotherapy. Results. The treatment proved to be effective in diminishing neurotic symptoms (d Cohen=0.56. More detailed analysis revealed that there was a significant interaction between the three analysed therapeutic wards and the effectiveness (.2=0.09. The treatments offered in two institutions were effective (d Cohen=0.80 while one of the programs did not lead to significant improvement of the patients. None of the therapeutic wards proved to be effective in changing the neurotic personality traits. Conlusions. There are significant differences in effectiveness of the intensive programs of treatment for neurotic and personality disorders. In the light of the literature, one can assume that the differences are more connected with the characteristics of therapeutic teams than with the methods used. The need for standard methods of effectiveness monitoring is discussed.

  3. COMPARISON OF THE THERAPEUTIC EFFECT OF AURICULAR ACUPUNCTURE, BODY ACUPUNCTURE AND COMBINATION OF AURICULAR PLUS BODY ACUPUNCTURE FOR TREATMENT OF SIMPLE OBESITY

    Institute of Scientific and Technical Information of China (English)

    魏群利; 刘志诚

    2001-01-01

    Objective: To observe the therapeutic effect of auricular acupuncture (AA), body acupuncture (BA) and AA+BA for treatment of simple obesity. Methods: A total of 195 cases of obesity patients including 8 males and 187 females were randomly divided into AA group (n=55), BA group (n=64) and AA+BA group (n=76). Acupuncture treatment was given to the patient once every other day, with 12 sessions being a therapeutic course. Results: After one course of treatment, of the 55 cases in AA group, 1 case (1.8%) was cured, 15 (27.3%) had marked improvement, 11 (20.0%) had improvement and 28 (50.9%) failed in treatment, with the total effective rate being 49.9%. In BA group, of the 64 cases, 11 (17.2%) were cured, 23 (35.9%) had striking improvement, 18 (28. 1%) had improvement and 12 (18.8%) failed in treatment, with an effective rate of 81.2%. In AA+ BA group, of the 76 cases, 16 (21.1% ) were cured, 35 (46.1% ) had significant amelioration, 20 (26.3%) had amelioration and 5 (6.6%) failed in treatment with the effective rate being 93.4%. Statistical analysis showed that the therapeutic effect of BA and AA+BA group was significantly superior to that of AA group (P<0.05) ; and that of AA+BA group was higher than that of BA group Conclusion: The therapeutic effect of BA and AA+BA was superior to that of AA in treatment of simple obesity.

  4. A Retrospective Analysis of 5,195 Patient Treatment Sessions in an Integrative Veterinary Medicine Service: Patient Characteristics, Presenting Complaints, and Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Justin Shmalberg

    2015-01-01

    Full Text Available Integrative veterinary medicine, the combination of complementary and alternative therapies with conventional care, is increasingly prevalent in veterinary practice and a focus of clinical instruction in many academic teaching institutions. However, the presenting complaints, therapeutic modalities, and patient population in an integrative medicine service have not been described. A retrospective analysis of 5,195 integrative patient treatment sessions in a veterinary academic teaching hospital demonstrated that patients most commonly received a combination of therapeutic modalities (39% of all treatment sessions. The 274 patients receiving multiple modalities were most frequently treated for neurologic and orthopedic disease (50.7% versus 49.6% of all presenting complaints, resp.. Older neutered or spayed dogs (mean age = 9.0 years and Dachshunds were treated more often than expected based on general population statistics. Acupuncture, laser therapy, electroacupuncture, and hydrotherapy were frequently administered (>50% patients. Neurologic patients were more likely to receive acupuncture, electroacupuncture, and therapeutic exercises but less likely than orthopedic patients to receive laser, hydrotherapy, or therapeutic ultrasound treatments (P<0.05. The results suggest that the application of these specific modalities to orthopedic and neurologic diseases should be subjected to increased evidence-based investigations. A review of current knowledge in core areas is presented.

  5. Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia.

    LENUS (Irish Health Repository)

    McCarthy, Fergus P

    2012-01-31

    Preeclampsia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-gamma agonist using the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. The selective PPAR-gamma agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-gamma activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tin-protoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-gamma agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preeclampsia, via a heme oxygenase 1-dependent pathway. The findings from this study provide further insight into the underlying etiology of preeclampsia and a potential therapeutic target for the treatment of preeclampsia.

  6. A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.; Narasimhan, Diwahar; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K.; Woods, James H. (Michigan); (Michigan-Med); (Kentucky)

    2010-09-03

    Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.

  7. [Therapeutic effect of intravaginal application of estriol tablets in the treatment of pathological cervical factor as a cause of sterility].

    Science.gov (United States)

    Kofler, E

    1984-04-01

    81 women were included in a prospective randomised 12-year personal study. The "pathological cervical factor" was confirmed by periovulatory daily examination of the quality of the cervical mucus, using a new modified scheme of cervical score by examining the oestrogenic activity in the vaginal smear and results of sperm-penetration tests after Sims- Huhner , partly also by periovulatory determination of the concentration of luteinising hormone in the serum. The presence of ovulatory cycles could also be determined by regular registration of the cycle length, measurement of the basal body temperature and partly by premenstrual endometrium biopsies; these determinations were of course effected during cycles without therapy. All 81 cases with abnormal preovulatory production of cervical mucus were treated in a total of 234 cycles by intravaginal application of oestriol tablets 1 to maximal 3 mg daily for 1 or more subsequent cycles. On the basis of these criteria, the quality of cervical mucus and postcoital tests improved with a satisfying intravaginal resorption of the oestriol tablets; no side effects were seen. After this therapy, very good results were obtained with intravaginally administered oestriol tablets in 59.3% of the patients with a pregnancy rate of 27.2%; 24.7% of the cases only showed a moderate improvement of the mucus; 16.0% did not respond to oestriol treatment and, therefore, had to be considered as therapeutic failures. The present study again confirms the results of other investigators on the local effectiveness of intravaginal application of oestriol tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Therapeutic options in the treatment of cartilage defects: techniques and indications; Therapieoptionen zur Behandlung von Knorpelschaeden: Techniken und Indikationen

    Energy Technology Data Exchange (ETDEWEB)

    Resinger, C.; Vecsei, V.; Marlovits, S. [Universitaetsklinik fuer Unfallchirurgie, Medizinische Universitaet Wien (Austria)

    2004-08-01

    Cartilage is composed of chondrocytes embedded within an extracellular matrix of collagens, proteoglycans, and noncollagenous proteins. Together, these structures maintain the unique mechanical properties and manifest its striking inability to heal even the most minor injury. This review presents the principles of cartilage structure and the biological background of cartilage repair and gives information about the surgical techniques for treating cartilage defects. The response of cartilage to injuries differs from that of other tissues because of its avascularity, the immobility of chondrocytes and the limited ability of mature chondrocytes to proliferate and alter their synthetic patterns. Surgical therapeutic efforts in treating cartilage defects have focused on bringing new cells and tissues capable of chondrogenesis into the lesions and facilitating the access to the vascular system. The right indication and the treatment of joint instability and axis deformation are essential for the successful use of cartilage repair procedures. (orig.) [German] Das artikulaere Knorpelgewebe besteht aus einer einzelnen Zellpopulation, integriert in ein dreidimensionales Netzwerk hochorganisierter Matrixstrukturen. Dieser feingewebliche Aufbau bestimmt die einzigartigen mechanischen Eigenschaften, limitiert aber auch die physiologischen Reparationsmoeglichkeiten von Knorpeldefekten. Diese Uebersicht beschreibt die Grundlagen der Knorpelbiologie und die Mechanismen der Knorpelreparatur und behandelt die klinischen Ergebnisse chirurgischer Techniken zur Therapie umschriebener Knorpeldefekte. Die chirurgischen Techniken zur Therapie lokalisierter Defekte der Gelenkoberflaeche versuchen durch die Integration biologischer Mechanismen die mangelnde Regenerationsfaehigkeit artikulaeren Knorpels zu ueberwinden. Die Techniken der Transplantation chondrogener Gewebe wurden in juengster Zeit durch die Defektauffuellung mit autologen Chondrozyten erweitert. Eine klare Indikationsstellung

  9. Thermal therapeutic method for selective treatment of deep-lying tissue by combining laser and high-intensity focused ultrasound energy.

    Science.gov (United States)

    Kim, Haemin; Kang, Jeeun; Chang, Jin Ho

    2014-05-01

    Photothermal therapy is performed by delivering laser radiation into the target lesion containing tissue chromophores so as to induce localized heating. For high treatment efficacy, the laser wavelength should be selected to maximize the absorption of incident laser radiation in the tissue chromophores. However, even with the optimal laser wavelength, both the absorption and the scattering of laser energy in tissue openly hamper treatment efficacy in deep-lying lesions. To overcome the limitation, we propose a dual thermal therapeutic method in which both laser and acoustic energies are transmitted to increase therapeutic depth while maintaining high target selectivity of photothermal therapy. Through skin-mimicking phantom experiments, it was verified that the two different energies are complementary in elevation of tissue temperature, and the treatment depth using laser radiation is increased along with acoustic energy.

  10. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Francisco de; Santas, Bernardo Maranhao; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: faraujo@ird.gov.br; Melo, Rossana Corbo de; Rebelo, Ana Maria de Oliveira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2007-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology to evaluate therapeutic doses through the determination of biokinetic parameters and the activity of {sup 131}I deposited in the thyroid of patients submitted to the treatment of hyperthyroidism with {sup 131}I. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The calculation of the calibration factor of the scintillation camera allows the determination of activities in the thyroid of patients in pre-established time periods through a 48-hours uptake curve. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were 39.3 {+-} 0.8 and 4.3 {+-} 0.2 respectively. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use

  11. Clinical Observation on the Therapeutic Effects of Heavy Moxibustion plus Point-injection in Treatment of Impotence

    Institute of Scientific and Technical Information of China (English)

    赵琍珏

    2004-01-01

    @@ Impotence, a common disease in males, can cause infertility. Since 1990, the author has been using heavy moxibustion and point-injection of VB12 to treat impotence, with satisfactory therapeutic results reported in the following.

  12. Therapeutic ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Crum, Lawrence A [Center for Industrial and Medical Ultrasound, 1013 NE 40th Street, University of Washington, Seattle, WA 98105 (United States)

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  13. 超声臭氧雾化治疗仪治疗阴道炎的临床观察%The therapeutic effects of ultrasonic ozone atomization therapeutic apparatus in the treatment of vaginitis

    Institute of Scientific and Technical Information of China (English)

    徐迎春

    2014-01-01

    目的:观察应用超声臭氧雾化治疗仪治疗阴道炎的临床疗效。方法选择我院收治并确诊为细菌性阴道炎、假丝酵母菌性阴道炎、滴虫性阴道炎的240例患者,其中160例患者进行超声臭氧雾化治疗仪治疗,80例患者予传统药物治疗。超声臭氧雾化治疗仪治疗的160例患者用清水棉球擦净阴道分泌物后,通过一次性导气头将臭氧治疗仪产生的臭氧混合气体引入阴道后穹隆,治疗10 min,每日1次,7次为1个疗程。疗程结束后观察患者治疗效果,并与经传统药物治疗的80例阴道炎患者的临床疗效进行比较。结果160例阴道炎患者经臭氧治疗后外阴瘙痒、阴道黏膜充血和阴道清洁度均有明显改善,总有效率达98.1%,平均缓解时间(2.5±0.5)d。经传统药物治疗的患者有效率为92.5%,平均缓解时间(3.8±0.8)d,2组比较具有显著统计学差异(P<0.05)。结论超声臭氧雾化治疗阴道炎的治愈率高,症状缓解时间缩短,且方法简便易操作,安全性较高,是临床上有效的物理治疗方法。%Objective To observe the therapeutic effects of ultrasonic ozone atomization therapeutic apparatus in the treatment of vaginitis. Methods 240 patients with bacterial vaginosis, candida vaginitis or chomoniasis vaginitis were recruited in our hospital and divided into two groups. 160 cases in the first group were treated using ultrasonic ozone atomization therapeutic apparatus and 80 cases in the second group were treated with conservative medication therapy. After cleaning the vaginal secretions, the 160 patients were treated with ozone gas produced by ozone atomization therapeutic apparatus for 10 minutes per day. The therapeutic effects were observed after 7-day treatment and the comparative study were conducted between these two different groups. Results The clinical symptoms, including vulvar itching, vaginal mucosa congestion and vaginal

  14. The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of tabun poisoning in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Pavlikova, Ruzena; Misik, Jan; Caisberger, Filip; Bajgar, Jiri

    2010-03-01

    The influence of the combination of oximes on the reactivating and therapeutic efficacy of antidotal treament of acute tabun poisoning was evaluated. The ability of two combinations of oximes (HI-6 + obidoxime and HI-6 + K203) to reactivate tabun-inhibited acetylcholinesterase and reduce acute toxicity of tabun was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, obidoxime, K203) using in vivo methods. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is higher than the reactivating efficacy of the most effective individual oxime in blood and diaphragm and comparable with the reactivating effects of the most effective individual oxime in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in tabun-poisoned mice than the antidotal treatment involving individual oxime. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the newly developed oxime K203 is slightly more effective than commonly used obidoxime and both of them are markedly more effective than the oxime HI-6. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings beneficial effects for the potency of antidotal treatment to reactivate tabun-inhibited acetylcholinesterase in rats and to reduce acute toxicity of tabun in mice.

  15. Platelet-derived growth factor receptor/platelet-derived growth factor (PDGFR/PDGF) system is a prognostic and treatment response biomarker with multifarious therapeutic targets in cancers.

    Science.gov (United States)

    Appiah-Kubi, Kwaku; Wang, Ying; Qian, Hai; Wu, Min; Yao, Xiaoyuan; Wu, Yan; Chen, Yongchang

    2016-08-01

    Progress in cancer biology has led to an increasing discovery of oncogenic alterations of the platelet-derived growth factor receptors (PDGFRs) in cancers. In addition, their overexpression in numerous cancers invariably makes PDGFRs and platelet-derived growth factors (PDGFs) prognostic and treatment markers in some cancers. The oncologic alterations of the PDGFR/PDGF system affect the extracellular, transmembrane and tyrosine kinase domains as well as the juxtamembrane segment of the receptor. The receptor is also involved in fusions with intracellular proteins and receptor tyrosine kinase. These discoveries undoubtedly make the system an attractive oncologic therapeutic target. This review covers elementary biology of PDGFR/PDGF system and its role as a prognostic and treatment marker in cancers. In addition, the multifarious therapeutic targets of PDGFR/PDGF system are discussed. Great potential exists in the role of PDGFR/PDGF system as a prognostic and treatment marker and for further exploration of its multifarious therapeutic targets in safe and efficacious management of cancer treatments.

  16. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

    Science.gov (United States)

    Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafò, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo

    2013-01-01

    Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  17. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

    Directory of Open Access Journals (Sweden)

    Nelly Mezzaroba

    Full Text Available Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  18. Chicanoizing the Therapeutic Community

    Science.gov (United States)

    Aron, William S.; And Others

    1974-01-01

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

  19. Regulation of appetite, satiation, and body weight by enteroendocrine cells. Part 2: therapeutic potential of enteroendocrine cells in the treatment of obesity.

    Science.gov (United States)

    Posovszky, Carsten; Wabitsch, Martin

    2015-01-01

    Obesity is an epidemic and medical issue. Investigating the pathways regulating appetite, food intake, and body weight is crucial to find strategies for the prevention and treatment of obesity. In the context of therapeutic strategies, we focus here on the potential of enteroendocrine cells (EECs) and their secreted hormones in the regulation of body weight. We review the role of the enteroendocrine system during weight loss after lifestyle intervention or after bariatric surgery. We discuss the therapeutic potential of EECs and their hormones as targets for new treatment strategies. In fact, targeting nutrient receptors of EECs with a nutritional approach, pharmaceutical agents or prebiotics delivered to the lumen may provide a promising new approach. © 2015 S. Karger AG, Basel.

  20. The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease.

    Science.gov (United States)

    Hollak, Carla E M; Weinreb, Neal J

    2015-03-01

    Enzyme replacement therapies have been developed and authorized for commercial use for six different lysosomal storage disorders. For Gaucher disease, Fabry disease and mucopolysaccharidosis type 1, disease-specific treatments have been available for more than a decade. Although long term follow-up data are still sparse, therapeutic goals for patients with Gaucher disease and Fabry disease have been formulated and published for both adults and children. Without adaptation or modification, these goals are often applied in clinical research and in routine patient care across the entire phenotypic spectrum of disease, although in practice, patients commonly manifest high variability in clinical presentation and course of the illness. In this context, establishing goals for the follow-up and treatment of late onset/attenuated phenotypes is particularly challenging. In this chapter, we review current therapeutic goals for Gaucher disease and Fabry disease and discuss approaches for those with attenuated disease manifestations.

  1. Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis.

    Science.gov (United States)

    Poucheret, Patrick; Fons, Françoise; Doré, Jean Christophe; Michelot, Didier; Rapior, Sylvie

    2010-06-15

    Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

  2. Use of virtual reality as therapeutic tool for behavioural exposure in the ambit of social anxiety disorder treatment

    DEFF Research Database (Denmark)

    Grillon, Helena; Riquier, Francoise; Herbelin, Bruno

    2006-01-01

    We hereby present a study whose aim is to evaluate the efficiency and flexibility of virtual reality as a therapeutic tool in the confines of a social phobia behavioural therapeutic program. Our research protocol, accepted by the ethical commission of the cantonal hospices’ psychiatry service......, is identical in content and structure for each patient. This study’s second goal is to use the confines of virtual exposure to objectively evaluate a specific parameter present in social phobia, namely eye contact avoidance, by using an eye-tracking system. Analysis of our results shows...

  3. Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma.

    Science.gov (United States)

    Incorvaia, Lorena; Bronte, Giuseppe; Bazan, Viviana; Badalamenti, Giuseppe; Rizzo, Sergio; Pantuso, Gianni; Natoli, Clara; Russo, Antonio

    2016-04-19

    The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

  4. [The pathogenetic substantiation of new therapeutic approach to the treatment of secondary osteoarthritis in patients with rheumatoid arthritis with basis therapy].

    Science.gov (United States)

    Starodubtseva, I A; Tsvetikova, L N

    2014-01-01

    The article concerns the efficacy of the use of new therapeutic approach in the therapy of secondary osteoarthritis in patients with rheumatoid arthritis. The dynamic of Cartilage Oligomeric Matrix Protein, activity of the disease on DAS28, cytokine profile was estimated. The analysis of the results showed the advantages of the use of inhibitor of IL-1 combined with laser therapy in the treatment of secondary osteoarthritis in patients with rheumatoid arthritis.

  5. O06TARGETING FOXM1 AS A NOVEL THERAPEUTIC STRATEGY FOR THE TREATMENT OF MSH6 DEFICIENT TEMOZOLOMIDE-RESISTANT GLIOBLASTOMA

    OpenAIRE

    Brierley, David J.; Locke, Matthew; Merve, Ashirwad; Marino, Silvia; Martin, Sarah A.

    2014-01-01

    INTRODUCTION: Mutations in the DNA mismatch repair gene MSH6 can arise in glioblastoma cells during Temozolomide treatment and can mediate drug resistance. Recently, exploiting the concept of synthetic lethality has been proposed as a therapeutic strategy. METHOD & RESULTS: Based on this approach we have identified the thiazole antibiotic Thiostrepton as synthetically lethal with MSH6 deficiency in the presence of Temozolomide, in vitro and in vivo. Our data suggest that in the absence of MSH...

  6. [Bipolar affective disorders and role of intraneuronal calcium. Therapeutic effects of the treatment with lithium salts and/or calcium antagonist in patients with rapid polar inversion].

    Science.gov (United States)

    Manna, V

    1991-11-01

    Treatment with lithium salts produces improvements in bipolar affective disorders. Up to date, the relationship between neurochemical and behavioural effects of lithium and its actions on intraneuronal free calcium ions is not well known. Some calcium antagonist drugs resulted active in the treatment of bipolar affective syndromes, with therapeutic effects similar to lithium salts. Some studies suggest that also lithium salts act as calcium antagonist at intraneuronal level. In this preliminary open study the activity of nimodipine, a selective neuronal calcium antagonist drug, was evaluated alone and in association with lithium salts in the treatment of rapid cycling bipolar manic-depressive illness. During three periods of 6 months 12 rapid cycling patients were treated with lithium salts, lithium salts plus nimodipine 30 mg x 3/day, nimodipine 30 mg x 3/day. The association of lithium with nimodipine resulted more effective than lithium alone or nimodipine alone in the reduction of episodes of affective disorder. These results suggest a probable sinergic activity of both treatments. Further studies will be necessary to confirm the mechanism of action, perhaps calcium antagonism, at the basis of therapeutic effects of both treatments. The results seem to confirm the hypothesis that a calcium-ionic disorders play a role in the pathogenesis of bipolar affective disorders.

  7. The role of therapists' treatment adherence, professional experience, therapeutic alliance, and clients' severity of psychological problems: Prediction of treatment outcome in eight different psychotherapy approaches. Preliminary results of a naturalistic study.

    Science.gov (United States)

    Tschuschke, Volker; Crameri, Aureliano; Koehler, Miriam; Berglar, Jessica; Muth, Katharina; Staczan, Pia; Von Wyl, Agnes; Schulthess, Peter; Koemeda-Lutz, Margit

    2015-01-01

    In this naturalistic study, 262 audiotaped psychotherapy sessions--randomly drawn from 81 individual therapies from eight different psychotherapy approaches--were rated completely on treatment adherence using a newly developed rating manual. In the therapy sessions, a relatively low percentage of treatment specific interventions (ranging from 4.2% to 27.8%) was found for all eight approaches, 50% to 73% of the interventions were nonspecific or common, and approximately 18% to 27% were intervention techniques from other approaches. Different types of psychotherapy differed highly significantly in levels of treatment adherence. There was no statistically significant association between the type of psychotherapy and its outcome, or between the degree of therapists' treatment fidelity and the treatment outcome. However, there were significant associations between therapists' degree of professional experience, clients' initial psychological burden, and treatment response. Clients' severity of psychological problems prior to treatment predicted quality of therapeutic alliance while therapists' treatment adherence was predicted by therapists' professional experience and by the quality of the therapeutic alliance. We discuss the seemingly indirect importance of treatment adherence for psychotherapy outcome that we found in this study in relation to findings from other studies and in the context of the role of schools within psychotherapy.

  8. Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

    Science.gov (United States)

    Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

    2017-09-01

    Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel

  9. Potential therapeutic applications of differentiated induced pluripotent stem cells (iPSCs) in the treatment of neurodegenerative diseases.

    Science.gov (United States)

    Gao, Aijing; Peng, Yuhua; Deng, Yulin; Qing, Hong

    2013-01-01

    Difficulties in realizing persistent neurogenesis, inabilities in modeling pathogenesis of most cases, and a shortage of disease material for screening therapeutic agents restrict our progress to overcome challenges presented by neurodegenerative diseases. We propose that reprogramming primary somatic cells of patients into induced pluripotent stem cells (iPSCs) provides a new avenue to overcome these impediments. Their abilities in self-renewal and differentiation into various cell types will enable disease investigation and drug development. In this review, we introduce efficient approaches to generate iPSCs and distinct iPSCs differentiation stages, and critically discuss paradigms of iPSCs technology application to investigate neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Although iPSCs technology is in its infancy and faces many obstacles, it has great potential in helping to identify therapeutic targets for treating neurodegenerative diseases.

  10. Sweet Syndrome due to Myelodysplastic Syndrome: Possible Therapeutic Role of Intravenous Immunoglobulin in Addition to Standard Treatment

    Directory of Open Access Journals (Sweden)

    Harry H. S. Gill

    2010-01-01

    Full Text Available We report an 82-year-old lady who developed sudden onset nodular and erythematous lesions and neutrophilia following an episode of urinary tract infection. Skin biopsy confirmed the diagnosis of Sweet syndrome. Response to the use of prednisolone alone was not satisfactory. The skin lesions however showed a sustained response to the regular use of intravenous immunoglobulin (IVIG and prednisolone was slowly weaned off. Our case highlights the possible therapeutic role of IVIG in managing this condition.

  11. Sweet Syndrome due to Myelodysplastic Syndrome: Possible Therapeutic Role of Intravenous Immunoglobulin in Addition to Standard Treatment.

    Science.gov (United States)

    Gill, Harry H S; Leung, Anskar Y H; Trendell-Smith, N J; Yeung, C K; Liang, Raymond

    2010-01-01

    We report an 82-year-old lady who developed sudden onset nodular and erythematous lesions and neutrophilia following an episode of urinary tract infection. Skin biopsy confirmed the diagnosis of Sweet syndrome. Response to the use of prednisolone alone was not satisfactory. The skin lesions however showed a sustained response to the regular use of intravenous immunoglobulin (IVIG) and prednisolone was slowly weaned off. Our case highlights the possible therapeutic role of IVIG in managing this condition.

  12. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.

  13. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

    Science.gov (United States)

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-12-22

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

  14. Metabonomic analysis of the therapeutic effect of Potentilla discolor in the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Li, Yi; Li, Jing-jing; Wen, Xiao-dong; Pan, Rong; He, Yi-sheng; Yang, Jie

    2014-11-01

    Type 2 diabetes mellitus (T2DM) is increased worldwide in parallel with the obesity epidemic. Potentilla discolor is one of the most important crude materials in Traditional Chinese medicine (TCM) for therapy of hyperglycemia and hyperlipidemia. In this work, a plasma metabonomic approach based on the combination of UPLC-Q-TOF with multivariate data analysis was applied to investigate the therapeutic effects of the extract of P. discolor (EPD) and corosolic acid (CA), the main bioactive compounds of P. discolor. Male C57BL/6 mice were fed with high-fat diet (HFD-fed group) for 8 weeks and then treated with EPD (EPD-treated group) or CA (CA-treated group) for another 8 weeks. After the experimental period, samples of plasma were collected and analyzed by ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF). The principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to find biomarkers of T2DM and investigate the therapeutic effects of EPD and CA. 26 metabolites, which are distributed in several metabolic pathways, were identified as potential biomarkers of T2DM. It was found that EPD and CA could reverse the pathological process of T2DM through regulating the disturbed pathway of metabolism. The metabonomic results are beneficial not only for the evaluation of the therapeutic effect of TCM but also for the elucidation of the underlying molecular mechanism.

  15. Successful long-term (22 year) treatment of limited scleroderma using therapeutic plasma exchange: Is blood rheology the key?

    Science.gov (United States)

    Harris, Edward S; Meiselman, Herbert J; Moriarty, Patrick M; Weiss, John

    2017-01-01

    While a number of studies have shown short-term beneficial effects of therapeutic plasma exchange (TPE) for treating systemic scleroderma (SSc), there have been no reports on the very long-term usage of TPE as the sole systemic treatment intervention. We report the case of a male patient, originally diagnosed with limited systemic scleroderma (lcSSc) in early 1990, who has been undergoing regular plasmapheresis treatments for more than 22 years, beginning in late 1993. Prior to commencing treatment, the patient exhibited symptoms including severe gastro esophageal reflux disease (GERD) with esophagitis, frequent Raynaud's attacks, reduced lung function, and chronic chilling. With the exception of mild residual Raynaud's, all of the patient's symptoms reversed after three years of regular TPE treatments and he remains in complete remission. While the typical explanation for the therapeutic benefits seen with TPE focuses on temporary reduction of circulating antibodies or other pathogenic factors, we propose instead an explanation based on abnormal blood rheology as a novel disease pathogenesis model for SSc.

  16. Treatment of Speech Difficulties and Body Tics Secondary to Childhood Sexual Trauma through a Combination of Hypnotic Age Regression and Therapeutic Coaching: A Case Report

    Directory of Open Access Journals (Sweden)

    Joseph Tramontana

    2015-09-01

    Full Text Available For years, when describing his therapeutic use of hypnosis to individual clients or in various presentations to professionals, the present author has referred to hypnosis as a “tool through which therapeutic change can be enhanced.” One such presentation was titled “Hypnosis as an Adjunct to Psychotherapy” [1]. In his book on hypnotically enhanced treatment for addictions [2] and various CEU workshops to ASCH and other groups [3-6] on addictions, and more recently one specifically on treatment for gambling addiction [7], he stressed that many therapies could be enhanced when presented hypnotically. Examples include cognitive behavioral approaches (CBT [8]; Yapko [9] described treatment of depression integrating CBT and hypnosis. CBT, Acceptance and Commitment Therapy (ACT, 12-step programs, healing the wounded child within, and others have been utilized in combination with hypnosis by the present author. One publication combining hypnosis with other therapies is titled “Hypnotic systematic desensitization” [10]. In an article on hypnotic approaches to chronic pain management, Jensen and Patterson [11] referred to a meta-analysis by Kirsch et al. [8]. They referred to “the additive effects of hypnosis” when combined with other treatments.

  17. EFFECT OF NEEDLING STIMULATION QUANTITY ON THE THERAPEUTIC EFFECT OF ACU-MOXIBUSTION IN THE TREATMENT OF PERIPHERAL FACIAL PALSY IN THE EARLY STAGE

    Institute of Scientific and Technical Information of China (English)

    倪莹莹

    2003-01-01

    Objective:To observe the correlation between needling stimulation quantity and the therapeutic effect of acupuncture in the treatment of early stage of peripheral facial palsy. Methods: Sixty-three peripheral facial palsy patients were randomized into treatment group (n=33) and control group (n=30). In treatment group, Taiyang (EX-HN 5), Jingming (BL 1) and Hegu (LI 4) were punctured with gauge-36 acupuncture needles and stimulated with light twirling-reinforcing method (about 200 times/min), the acupuncture needles were retained for 20 min. In addition, moxibustion was also applied to Fengchi (GB 20) and Qianzheng (EX-HN 17) following puncturing them with gauge-30 filiform needles. In control group, conventional twirling-reducing method (about 60 times/min) was applied to Yangbai (GB 14), Cuanzhu (BL 2), Sizhukong (TE 23), etc., following puncturing them with gauge-28 filiform needles. Additionally, thermal needle was applied to Fengchi (GB 20), Yifeng (TE 17) and Jiache (ST 6), with the needles retained for 40 min. Results: Following 10 days' treatment, of the 33 and 30 cases in treatment and control groups, 21 (63.0%) and 12 (40.0%) were cured, 7(21.1%) and 5 (16.7%) had remarkable improvement, 4 (12.1%) and 9 (30.0%) were effective, and 1 (3.0%) and 4 (13.3%) failed in the treatment, with the cure plus markedly effective rates being 84.8% and 56.7% respectively. Statistical analysis shows that in acupuncture treatment of early stage of facial palsy, light stimulation is superior to that of heavy stimulation in the therapeutic effect.

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

    Science.gov (United States)

    Toledo-Sherman, Leticia M; Prime, Michael E; Mrzljak, Ladislav; Beconi, Maria G; Beresford, Alan; Brookfield, Frederick A; Brown, Christopher J; Cardaun, Isabell; Courtney, Stephen M; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L; O'Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A; Went, Naomi E; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia

    2015-02-12

    We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

  20. Clinical application research on the use of the Photon Therapeutic Apparatus combined with Hops extract compound ointment in treatment for breast cancer patients

    Directory of Open Access Journals (Sweden)

    Chen Yunzhu

    2017-01-01

    Full Text Available Objective: To research Carnation-87C photon theraapeutic apparatus combine with compound hops extract ointment in the clinical effect of breast cancer patients after operation with unhealed incision of skin flap necrosis. Method: The experimental group is treated by the conventional therapy and Carnation-87C photon therapeutic apparatus combine with compound hops extract ointment, while the control group is treated by the conventional therapy only, such as regular dressing change. The other treatments for two groups of patients are the same. Through 4 weeks’ treatment, the growth of fresh granulation tissue and healing time were observed between two groups. Results: There were statistically significant differences (P<0.05 in the growth of fresh granulation tissue and healing time between two groups of patients with non-healing skin flap necrosis after the operation. Conclusion: The treatment with the Carnation-87C photon therapeutic apparatus combine with compound hops extract ointment for breast cancer patients after operation with unhealed incision of skin flap necrosis is easy to operate with good curative effect, and it is worth popularizing in clinical application.

  1. Therapeutic Method of External Treatment of Chinese Medicinein in Exogenous Fever in Children%小儿外感发热中医外治法概述

    Institute of Scientific and Technical Information of China (English)

    魏理珍; 许丽

    2012-01-01

    Objective:To summarize the therapeutic method of external treatment of Chinese medicinein in exogenous fever in Children. Methods;To analysis the literatures about TCM external therapies in the Late IS Years. Results:The therapeutic methods of external treatment in exogenous fever in Children mainly are as follows:acupuncture therapy,massage therapy,pricking blood therapy,GuaSha therapy,cupping therapy,application therapy,nasal drops therapy,atomization therapy,rectal administration therapy,sponge bath therapy and so on. Conclusion:There are enough methods of TCM external treatment methods in exogenous fever in Children.%目的:总结小儿外感发热的中医外治法.方法:分析近15 a治疗小儿外感发热的外治法文献.结果:治疗小儿外感发热方法主要有:针灸、推拿、刺血疗法、刮痧、拔罐、敷贴、滴鼻、雾化、直肠给药、擦浴等.结论:中医外治法治疗小儿外感发热方法多样,疗效较好.

  2. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  3. Therapeutic Observation on Treatment of 68 Cases of Prolapse of Lumbar Intervertebral Disc with Lumber Vertebral Traction plus Ding's Rolling Technique

    Institute of Scientific and Technical Information of China (English)

    叶建兴; 朱函亭

    2007-01-01

    Objective: To observe the clinical therapeutic efficacy of treatment of prolapse of lumbar intervertebral disc with lumber vertebral traction plus Ding's Rolling Technique.Methods: 133 cases of prolapse of lumbar intervertebral disc were randomly divided into two groups. There were 68 cases in the treatment group, which were treated with lumber vertebral traction plus Tuina. There were 65 cases in the control group, which were treated with simple lumber vertebral traction. Results: There were statistic differences in the two groups (x2=6.86,P<0.01). The therapeutic efficacy in the treatment group was better than the control group.Conclusion: The clinical therapeutic efficacy treated with lumber vertebral traction plus Ding's Rolling Technique was better than simple lumber vertebral traction in treating prolapse of lumbar intervertebral disc.%目的:观察腰椎牵引后结合丁氏滚法推拿治疗腰椎间盘突出症的临床疗效.方法:将133例腰椎间盘突出症患者随机分为两组,治疗组68例,采用腰椎牵引后结合推拿治疗;对照组65例,采用单纯腰椎牵引治疗.结果:两组差异有统计学意义(x2=6.86,P<0.01),治疗组效果显著优于对照组.结论:腰椎牵引后结合丁氏滚法推拿治疗腰椎间盘突出症的临床疗效优于单纯采用腰椎牵引治疗.

  4. New Therapeutic Approaches for the Treatment of Rheumatoid Arthritis may Rise from the Cholinergic Anti-Inflammatory Pathway and Antinociceptive Pathway

    Directory of Open Access Journals (Sweden)

    Xiao Hua Pan

    2010-01-01

    Full Text Available Due to the complex etiology of rheumatoid arthritis (RA, it is difficult to be completely cured at the current stage although many approaches have been applied in clinics, especially the wide application of nonsteroidal anti-inflammatory drugs (NSAIDs and disease-modifying antirheumatic drugs (DMARDs. New drug discovery and development via the recently discovered cholinergic anti-inflammatory and antinociceptive pathways should be promising. Based on the above, the nicotinic acetylcholine receptor agonists maintain the potential for the treatment of RA. Therefore, new therapeutic approaches may rise from these two newly discovered pathways. More preclinical experiments and clinical trials are required to confirm our viewpoint.

  5. OBSERVATION ON THE THERAPEUTIC EFFECT OF NEEDLING IN COMBINATION WITH HERBAL MEDICINES FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

    Institute of Scientific and Technical Information of China (English)

    HE Qing-yong; ZHANG Ji

    2006-01-01

    Objective: To discover the effective therapy for the treatment of rheumatoid arthritis. Methods:A total of 62 patients were randomly divided into treatment group (30 cases) and control group (32 cases).The treatment group were punctured with filiform needle [Dazhui (大椎 GV 14), Zhiyang (至阳 GV 9), Ming-men (命门 GV 4), Shenting (神庭 GV 24), Hegu (合谷 LI 4) and Zusanli (足三里 ST 36) were used as main points] in combination with oral taking herbal medicines, and the control group only took herbal medicines,and the clinical effects of two groups were observed. Result: At the end of the first course of treatment, the total effective rate between treatment group (93.3%) and control group (87.5%) was obvious significant (P<0.05). At the end of the second course of treatment, the total effective rate between treatment grou