Novel therapeutic approaches in chondrosarcoma.

PubMed

Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

2017-03-01

Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

PubMed

Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

2017-01-01

Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Hypercholesterolemia: a therapeutic approach].

PubMed

Moráis López, A; Lama More, R A; Dalmau Serra, J

2009-05-01

High blood cholesterol levels represent an important cardiovascular risk factor. Hypercholesterolemia is defined as levels of total cholesterol and low-density lipoprotein cholesterol above 95th percentile for age and gender. For the paediatric population, selective screening is recommended in children older than 2 years who are overweight, with a family history of early cardiovascular disease or whose parents have high cholesterol levels. Initial therapeutic approach includes diet therapy, appropriate physical activity and healthy lifestyle changes. Drug treatment should be considered in children from the age of 10 who, after having followed appropriate diet recommendations, still have very high LDL-cholesterol levels or moderately high levels with concomitant risk factors. In case of extremely high LDL-cholesterol levels, drug treatment should be taken into consideration at earlier ages (8 years old). Modest response is usually observed with bile acid-binding resins. Statins can be considered first-choice drugs, once evidence on their efficacy and safety has been shown.

[Adipose-derived stromal cells (ASC) - basics and therapeutic approaches in otorhinolaryngology].

PubMed

Frölich, K; Hagen, R; Kleinsasser, N

2014-06-01

Adipose-derived Stromal Cells (ASC) - Basics and Therapeutic Approaches in Otorhinolaryngology Mesenchymal stem cells from adipose tissue can be easily harvested with less discomfort, low donor-site morbidity and high amount compared to bone marrow-derived stem cells. Due to their multilineage differentiation potential in various cell types, immunmodulatory properties and their capability to enhance wound healing, ASC are a promising cell source for tissue engineering approaches and regenerative medicine. They are characterized by the expression of specific surface marker proteins and their differentiation potential into the mesenchymal lineages. Whereas only preclinical studies are published for otorhinolaryngology-related therapeutic options using ASC, various diseases, for instance graft-versus-host disease, have already been treated with ASC in single cases or clinical trials. Safety and genomic stability of ASC as well as the risk of spontaneous malignant transformation are still disputed. This review summarizes the current literature on characterization and anatomic localization of ASC. In addition, beside the presentation of preclinical studies concerning therapeutic approaches in otorhinolaryngology as well as of current clinical applications, the issue of safety of ASC in human stem cell therapy is discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Cancer Terminator Viruses and Approaches for Enhancing Therapeutic Outcomes

PubMed Central

Das, Swadesh K.; Sarkar, Siddik; Dash, Rupesh; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

2015-01-01

No single or combinatorial therapeutic approach has proven effective in decreasing morbidity or engendering a cure of metastatic cancer. In principle, conditionally replication-competent adenoviruses that induce tumor oncolysis through cancer-specific replication hold promise for cancer therapy. However, a single-agent approach may not be adequate to completely eradicate cancer in a patient because most cancers arise from abnormalities in multiple genetic and signal transduction pathways and targeting disseminated metastases is difficult to achieve. Based on these considerations, a novel class of cancer destroying adenoviruses have been produced, cancer terminator viruses (CTVs), in which cancer-specific replication is controlled by the progression-elevated gene-3 promoter and replicating viruses produce a second transgene encoding an apoptosis-inducing and immunomodulatory cytokine, either melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) or interferon-γ. This review focuses on these viruses and ways to improve their delivery systemically and enhance their therapeutic efficacy. PMID:23021240

Novel unconventional therapeutic approaches to atopic eczema.

PubMed

Worm, M; Henz, B M

2000-01-01

Atopic eczema is a chronic, recurrent, multifactorial skin disease, and, accordingly, there are numerous therapeutic options for its symptomatic treatment. Conventional medications are however often unsatisfactory for many patients because of adverse effects on long-term use. For this reason, patients often readily welcome unconventional therapeutic approaches. We present here a selected number of such treatment modalities, namely gamma-linolenic acid, Chinese herbal tea, diets eliminating allergens, pseudoallergens, metal salts and sodium, and bioresonance. When stringent scientific criteria are applied in the evaluation of such study results, none of the reviewed alternative treatments provides unequivocal, convincing evidence of its efficacy, even when double-blind, placebo-controlled studies are available. With Chinese herbal tea, potentially serious adverse effects should be considered as well. Any new type of unconventional therapy should thus be thoroughly evaluated and shown to be equal or superior to conventional treatments with regard to both efficacy and tolerability before it is recommended for use in clinical practice. Copyright 2000 S. Karger AG, Basel.

Therapeutic approaches of leptin in Alzheimer's disease.

PubMed

Carro, Eva M

2009-11-01

Novel approaches in the understanding of the neurodegeneration observed in Alzheimer's disease (AD), involving neurochemical as well as biochemical techniques are being developed, opening up new possibilities in the direction of a metabolic degeneration. Indeed, brain lipids are closely involved in amyloid beta-related pathogenic pathways. An important modulator of lipid homeostasis is the pluripotent peptide leptin, which has been shown to reduce amyloid beta levels and tau-related pathological pathways, the major pathological hallmarks of AD. These data suggest that leptin holds promise as a novel therapeutic tool for AD. In this article, with some patent literature we will review here some of the most promising approaches involving leptin to cure and prevent, rather than to treat, AD symptoms.

Translational epigenetics: clinical approaches to epigenome therapeutics for cancer.

PubMed

Selcuklu, S Duygu; Spillane, Charles

2008-01-01

Cancer epigenetics research is now entering an exciting phase of translational epigenetics whereby novel epigenome therapeutics is being developed for application in clinical settings. Epigenetics refers to all heritable and potentially reversible changes in gene or genome functioning that occurs without altering the nucleotide sequence of the DNA. A range of different epigenetic "marks" can activate or repress gene expression. While epigenetic alterations are associated with most cancers, epigenetic dysregulation can also have a causal role in cancer etiology. Epigenetically disrupted stem or progenitor cells could have an early role in neoplastic transformations, while perturbance of epigenetic regulatory mechanisms controlling gene expression in cancer-relevant pathways will also be a contribution factor. The reversibility of epigenetic marks provides the possibility that the activity of key cancer genes and pathways can be regulated as a therapeutic approach. The growing availability of a range of chemical agents which can affect epigenome functioning has led to a range of epigenetic-therapeutic approaches for cancer and intense interest in the development of second-generation epigenetic drugs (epi-drugs) which would have greater specificity and efficacy in clinical settings. The latest developments in this exciting arena of translational cancer epigenetics were presented at a recent conference on "Epigenetics and New Therapies in Cancer" at the Spanish National Cancer Research Center (CNIO), Spain.

An alternative approach to recovering valuable metals from zinc phosphating sludge.

PubMed

Kuo, Yi-Ming

2012-01-30

This study used a vitrification process (with good potential for commercialization) to recover valuable metals from Zn phosphating sludge. The involved vitrification process achieves two major goals: it transformed hazardous Zn phosphating sludge into inert slag and it concentrated Fe (83.5%) and Zn (92.8%) into ingot and fine particulate-phase material, respectively. The Fe content in the ingot was 278,000 mg/kg, making the ingot a potential raw material for iron making. The fine particulate-phase material (collected from flue gas) contained abundant Zn (544,000 mg/kg) in the form of ZnO. The content (67.7%) of ZnO was high, so it can be directly sold to refineries. The recovered coarse particulate-phase material, with insufficient amount of ZnO, can be recycled as a feeding material for Zn re-concentration. Therefore, the vitrification process can not only treat hazardous materials but also effectively recover valuable metals. Copyright © 2011 Elsevier B.V. All rights reserved.

Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases.

PubMed

Gabathuler, Reinhard

2010-01-01

The central nervous system is protected by barriers which control the entry of compounds into the brain, thereby regulating brain homeostasis. The blood-brain barrier, formed by the endothelial cells of the brain capillaries, restricts access to brain cells of blood-borne compounds and facilitates nutrients essential for normal metabolism to reach brain cells. This very tight regulation of the brain homeostasis results in the inability of some small and large therapeutic compounds to cross the blood-brain barrier (BBB). Therefore, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. In this review, we will address the different approaches used to increase the transport of therapeutics from blood into the brain parenchyma. We will mainly concentrate on the physiologic approach which takes advantage of specific receptors already expressed on the capillary endothelial cells forming the BBB and necessary for the survival of brain cells. Among all the approaches used for increasing brain delivery of therapeutics, the most accepted method is the use of the physiological approach which takes advantage of the transcytosis capacity of specific receptors expressed at the BBB. The low density lipoprotein receptor related protein (LRP) is the most adapted for such use with the engineered peptide compound (EPiC) platform incorporating the Angiopep peptide in new therapeutics the most advanced with promising data in the clinic.

New therapeutic approaches for treatment of tularaemia: a review.

PubMed

Boisset, Sandrine; Caspar, Yvan; Sutera, Vivien; Maurin, Max

2014-01-01

Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline), and the aminoglycosides (streptomycin and gentamicin). 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. These new strategies have been evaluated in vitro, in axenic media and cell culture systems and/or in animal models. 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 was 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

New therapeutic approaches for treatment of tularaemia: a review

PubMed Central

Boisset, Sandrine; Caspar, Yvan; Sutera, Vivien; Maurin, Max

2014-01-01

Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline), and the aminoglycosides (streptomycin and gentamicin). 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. These new strategies have been evaluated in vitro, in axenic media and cell culture systems and/or in animal models. 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 was 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

Bacteriophage--a common divergent therapeutic approach for Alzheimer's disease and type II diabetes mellitus.

PubMed

Sohrab, Sayed S; Karim, Sajjad; Kamal, Mohammad A; Abuzenadah, Adel M; Chaudhary, Adeel G; Al-Qahtani, Mohammed H; Mirza, Zeenat

2014-04-01

Alzheimer's disease, the most important neurodegenerative disorder, is an irreversible, age-dependent disease of the brain characterized by problems in progressive impairments in memory, language, reasoning, behavior and visuospatial skills. It is characterized by the deposition of amyloid beta peptide, forming compact fibrillar plaques and neurofibrillary tau tangles. Another major and much more prevalent cause of morbidity and mortality in world is diabetes especially type 2 diabetes mellitus. It is caused by a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. Chronic wounds caused by antibiotic resistant bacterial infections that fail to heal are a common complication of diabetes mellitus and the most frequent reason for nontraumatic lower limb amputation. Holistically, these two diseases are linked at molecular level but the exact mechanism is a topic of debate. Bacteriophages are viruses infecting bacteria and lack ability to infect mammalian cells. They are neither causative agent for Alzheimer's disease or type 2 diabetes mellitus nor involved in their pathogenicity but promises for a novel divergent therapeutic approach. The great versatility of the phage system has led to the development of improved phage delivery vectors, as well as immunomodulation of anti-amyloid beta peptide response. Phages could also constitute valuable prophylaxis against bacterial infections, especially in immunocompromised patients like in the case of diabetes. Patients having diabetes have a high risk of developing foot ulcers which are difficult to be treated by antibiotics alone due to ever increasing antibiotic resistance strains. Combination therapy based on multiple phage and broad spectrum antibiotics holds great promise. The potential therapeutic phage therapy arises from its lack of natural tropism for mammalian cells, resulting in no adverse effects.

Cardiac Sarcoidosis: Clinical Manifestations, Imaging Characteristics, and Therapeutic Approach

PubMed Central

Houston, Brian A; Mukherjee, Monica

2014-01-01

Sarcoidosis is a multi-system disease pathologically characterized by the accumulation of T-lymphocytes and mononuclear phagocytes into the sine qua non pathologic structure of the noncaseating granuloma. Cardiac involvement remains a key source of morbidity and mortality in sarcoidosis. Definitive diagnosis of cardiac sarcoidosis, particularly early enough in the disease course to provide maximal therapeutic impact, has proven a particularly difficult challenge. However, major advancements in imaging techniques have been made in the last decade. Advancements in imaging modalities including echocardiography, nuclear spectroscopy, positron emission tomography, and magnetic resonance imaging all have improved our ability to diagnose cardiac sarcoidosis, and in many cases to provide a more accurate prognosis and thus targeted therapy. Likewise, therapy for cardiac sarcoidosis is beginning to advance past a “steroids-only” approach, as novel immunosuppressant agents provide effective steroid-sparing options. The following focused review will provide a brief discussion of the epidemiology and clinical presentation of cardiac sarcoidosis followed by a discussion of up-to-date imaging modalities employed in its assessment and therapeutic approaches. PMID:25452702

Three Valuable Peptides from Bee and Wasp Venoms for Therapeutic and Biotechnological Use: Melittin, Apamin and Mastoparan

PubMed Central

Moreno, Miguel; Giralt, Ernest

2015-01-01

While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of these venoms are now being studied with the aim to design and develop new therapeutic drugs. Far from evaluating the extensive number of monographs, journals and books related to bee and wasp venoms and the therapeutic effect of these toxins in numerous diseases, the following review focuses on the three most characterized peptides, namely melittin, apamin, and mastoparan. Here, we update information related to these compounds from the perspective of applied science and discuss their potential therapeutic and biotechnological applications in biomedicine. PMID:25835385

Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

PubMed Central

Llorens-Martín, María; Hernández, Félix; Avila, Jesús

2013-01-01

Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field. PMID:23690659

Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

PubMed

Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

2017-01-06

Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

Therapeutic Recreation in the Community: An Inclusive Approach. Second Edition

ERIC Educational Resources Information Center

Carter, Marcia Jean; LeConey, Stephen P.

2004-01-01

The second edition of Therapeutic Recreation in the Community: An Inclusive Approach reflects the changing and evolving nature of recreation and health care services. A number of social, economic, and political directives and technological advancements have fostered recreation in the community for all individuals. Due in part to a rising awareness…

[Enuresis aetological approaches and therapeutic strategies (author's transl)].

PubMed

Holm-Hadulla, M

1980-06-01

Enuresis is a frequent disease in childhood--entailing personal misery, shame, and discredit for the children concerned as well as irritation and a bigger workload for the responsible adults. Parents and teachers often tend to react to this uncontrolled urinating as to a personal provocation. The following study is meant to summarize different aetiological approaches from which therapeutic strategies are derived and classified according to pragmatic considerations. By resorting to common psychotherapeutic methods pediatricians can successfully treat 2/3--3/4 of all cases.

What is the best therapeutic approach to methicillin-resistant Staphylococcus aureus pneumonia?

PubMed

Peyrani, Paula; Ramirez, Julio

2015-04-01

The purpose of this review is to define what the best therapeutic approach is for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Although two meta-analyses reported conflicting findings, recent retrospective studies reported higher success rates in patients with MRSA pneumonia treated with linezolid when compared to vancomycin. Only registration trials are available for some anti-MRSA antibiotics, such as telavancin, ceftaroline, and ceftobiprole. Scarce information is available regarding the best therapeutic approach for MRSA community-acquired pneumonia. Linezolid seems to be a better choice than vancomycin for the treatment of MRSA ventilator-associated pneumonia. It is still unclear whether this affirmation holds for other forms of MRSA pneumonia. Further research is needed to define whether newer antibiotics are better alternatives than currently recommended agents.

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

PubMed Central

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

"Difficult" Colorectal Polyps - Therapeutic Approach.

PubMed

Alecu, M; Simion, L; Ionescu, S; Brătucu, E; Straja, N D

2015-01-01

Endoscopic polypectomy is the gold standard in the treatment of colorectal polyps. The importance of polypectomy rests primarily on the fact that polyp-type lesions present a high risk of malignant degeneration, colorectal polyps being able, if left unattended therapeutically, to generate a colorectal cancer (CRC) - a lesion with a far more negative prognosis. Although preferable, endoscopic polypectomy of colorectal polyps is not always possible, multiple factors generating difficulties in performing this therapeutic measure. We performed a retrospective study in the First Surgical Clinic of the "Prof. Dr. Alexandu Trestioreanu" Bucharest Oncology Institute, spanning a period of 3 years (2008-2011), in which time 224 patients were diagnosed by colonoscopy with colorectal polyps, of whom 222 patients benefited from endoscopic polypectomy. The aim of the study was to identify "difficult" polyps and to identify the criteria for endoscopic surgery versus classic surgery as a therapeutic indication. Presence of "difficult" polyps was observed in 37.56% of the patients diagnosed with colorectal polyps. In over 88% of cases endoscopic polypectomy was possible, and for the remaining patients classic surgery was the therapeutic solution opted for. Presence of "difficult" polyps generates inconveniences in performing endoscopic polypectomy, increasing the risk of postoperative complication occurrence, as well as the duration of the operation. If the criteria for characterizing polyps as "difficult" are relatively well-established, the choice between endoscopic and classic surgery as a therapeutic measure is left at the free will of the operating surgeon, with the exception of situations in which classic surgery is resorted to for oncological reasons. Celsius.

Retroperitoneal schwannomas: dilemmas in diagnostic approach and therapeutic management.

PubMed

Mastoraki, Aikaterini; Toska, Felicia; Tsiverdis, Ioannis; Kyriazi, Maria; Tsagkas, Athanasios; Danias, Nikolaos; Smyrniotis, Vasilios; Arkadopoulos, Nikolaos

2013-12-01

Schwannomas are rare tumors arising from Schwan cells of the peripheral nerve sheath. The majority of the cases are sporadic and familial clustering is often observed in association with von Rechlinghausen's disease. Cases of intrasacral (osseous) and spinal tumors have also been described. Histologically, schwannomas are distinguished by the presence of areas of high and low cellularity called Antoni A and B tissue, respectively. Clinical features are highly non-specific and depend on the location and size of the lesion, with abdominal pain and neurological deficit being the most common abnormalities. Radiological studies are fundamental in the diagnostic evaluation of RSs. Despite recent research on the therapeutic strategies against RS, surgical resection appears the only potentially curative approach. Unfortunately, a mere minority of patients is eligible to undergo surgical intervention. In addition, surgical removal of RS does not necessarily guarantee patient's long-term survival. Laparoscopic approach and enucleation of the tumor have been suggested as well. Alternative therapies, such as radio- and chemotherapy often proved insufficient. The aim of this review was to evaluate the results of surgical treatment for RS with special reference to the extent of its histological spread and to analyze the recent literature in order to provide an update on the current concepts of therapeutic management of this entity.

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

PubMed

Kim, Ye-Ram; Yang, Chul-Su

2017-09-28

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

Chapter One---Cancer terminator viruses and approaches for enhancing therapeutic outcomes.

PubMed

Das, Swadesh K; Sarkar, Siddik; Dash, Rupesh; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

2012-01-01

No single or combinatorial therapeutic approach has proven effective in decreasing morbidity or engendering a cure of metastatic cancer. In principle, conditionally replication-competent adenoviruses that induce tumor oncolysis through cancer-specific replication hold promise for cancer therapy. However, a single-agent approach may not be adequate to completely eradicate cancer in a patient because most cancers arise from abnormalities in multiple genetic and signal transduction pathways and targeting disseminated metastases is difficult to achieve. Based on these considerations, a novel class of cancer destroying adenoviruses have been produced, cancer terminator viruses (CTVs), in which cancer-specific replication is controlled by the progression-elevated gene-3 promoter and replicating viruses produce a second transgene encoding an apoptosis-inducing and immunomodulatory cytokine, either melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) or interferon-γ. This review focuses on these viruses and ways to improve their delivery systemically and enhance their therapeutic efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

BET inhibitors in cancer therapeutics: a patent review.

PubMed

Ghoshal, Anirban; Yugandhar, D; Srivastava, Ajay Kumar

2016-01-01

Inhibition of Bromodomain and Extra Terminal (BET) proteins is an emerging approach for developing advanced cancer therapeutics. In 2015, at least thirty patents have been published for developing cancer chemotherapeutics by targeting BET. Currently there are seven small molecule BET inhibitors in various stages of clinical trials for the development of anti-cancer drugs. Important patents focusing on development of BET inhibitors as potential cancer therapeutics published in 2015 have been covered. The reports are presented together with a review of the related structural chemical space. This review mainly focuses on the therapeutic applications, chemical class and structural modifications along with the molecules currently in clinical trials. BET sub-family proteins are one of the emerging targets to develop anti-cancer agents. Although many research groups have demonstrated the rationality of BET inhibition to combat cancer, a detailed molecular study needs to be performed to investigate the affected biological pathways. Selectivity among BET proteins should be kept in mind while developing BET inhibitors. In-silico molecular modelling studies can also provide valuable information for designing selective BET inhibitors towards anti-cancer drug discovery and development.

Bioactive compounds of sea cucumbers and their therapeutic effects

NASA Astrophysics Data System (ADS)

Shi, Shujuan; Feng, Wenjing; Hu, Song; Liang, Shixiu; An, Nina; Mao, Yongjun

2016-05-01

Sea cucumbers belong to the Class Holothuroidea of marine invertebrates. They are commercially valuable and prized as a food and folk medicine in Asia. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as vitamins, minerals and amino acids. A number of unique biological and pharmacological activities/properties, including anticancer, anticoagulant/antithrombotic, antimicrobial, antioxidant, antihyperlipidemic, antihyperglycemic, anti-inflammatory, antihypertension and radioprotective, have been ascribed to various compounds isolated from sea cucumbers. The therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives, especially triterpene glycosides, acid mucopolysaccharide, sphingoid bases, glycolipids, fucosylated chondroitin sulfate, polysaccharides, phospholipids, cerebrosides, phosphatidylcholines, and other extracts and hydrolysates. This review highlights the valuable bioactive components as well as the multiple therapeutic properties of sea cucumbers with a view to exploring their potential uses as functional foods and a natural source of new multifunctional drugs.

New approaches to molecular cancer therapeutics.

PubMed

Collins, Ian; Workman, Paul

2006-12-01

Cancer drug development is leading the way in exploiting molecular biological and genetic information to develop "personalized" medicine. The new paradigm is to develop agents that target the precise molecular pathology driving the progression of individual cancers. Drug developers have benefited from decades of academic cancer research and from investment in genomics, genetics and automation; their success is exemplified by high-profile drugs such as Herceptin (trastuzumab), Gleevec (imatinib), Tarceva (erlotinib) and Avastin (bevacizumab). However, only 5% of cancer drugs entering clinical trials reach marketing approval. Cancer remains a high unmet medical need, and many potential cancer targets remain undrugged. In this review we assess the status of the discovery and development of small-molecule cancer therapeutics. We show how chemical biology approaches offer techniques for interconnecting elements of the traditional linear progression from gene to drug, thereby providing a basis for increasing speed and success in cancer drug discovery.

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies

PubMed Central

Mueller, Alan J.; Peffers, Mandy J.; Proctor, Carole J.

2017-01-01

ABSTRACT Systems orientated research offers the possibility of identifying novel therapeutic targets and relevant diagnostic markers for complex diseases such as osteoarthritis. This review demonstrates that the osteoarthritis research community has been slow to incorporate systems orientated approaches into research studies, although a number of key studies reveal novel insights into the regulatory mechanisms that contribute both to joint tissue homeostasis and its dysfunction. The review introduces both top‐down and bottom‐up approaches employed in the study of osteoarthritis. A holistic and multiscale approach, where clinical measurements may predict dysregulation and progression of joint degeneration, should be a key objective in future research. The review concludes with suggestions for further research and emerging trends not least of which is the coupled development of diagnostic tests and therapeutics as part of a concerted effort by the osteoarthritis research community to meet clinical needs. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1573–1588, 2017. PMID:28318047

Understanding Neuropathic Corneal Pain-Gaps and Current Therapeutic Approaches

PubMed Central

Goyal, Sunali; Hamrah, Pedram

2017-01-01

The richly innervated corneal tissue is one of the most powerful pain generator in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain. PMID:26959131

An innovative and highly drug-tolerant approach for detecting neutralizing antibodies directed to therapeutic antibodies.

PubMed

Sloan, John H; Conway, Richard G; Pottanat, Thomas G; Troutt, Jason S; Higgs, Richard E; Konrad, Robert J; Qian, Yue-Wei

2016-10-01

Immunogenicity testing of biotherapeutic drugs is a regulatory requirement. Herein, we describe a drug-tolerant assay for detecting neutralizing antibodies against a therapeutic antibody. Excess target of the therapeutic antibody was incorporated into the detection step of an affinity capture elution assay. Signal generated from binding of antidrug antibody (ADA) to the therapeutic antibody was compared with signal from binding of ADA to the therapeutic antibody preincubated with its target. The results demonstrated that the target blocked binding of the therapeutic antibody to neutralizing monkey ADA and to two anti-idiotypic antibodies. This highly drug-tolerant novel approach enables the detection of neutralizing antibodies and allows for one basic assay format to achieve complete characterization of ADA responses.

Novel therapeutic approach targeting the HIF-HRE system in the kidney.

PubMed

Nangaku, Masaomi

2009-01-01

Recent studies emphasize the role of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease. Therefore, therapeutic approaches which target the chronic hypoxia should prove effective against a broad range of renal diseases. Many of hypoxia-triggered protective mechanisms are hypoxia inducible factor (HIF)-dependent. Although HIF-1 alpha and HIF-2 alpha share both structural and functional similarity, they have different localization and can contribute in a non-redundant manner. While gene transfer of constitutively active HIF has been shown effective, pharmacological approaches to activate HIF are more desirable. Oxygen-dependent activation of prolyl hydroxylases (PHD) regulates the amount of HIF by degradation of this transcription factor. Therefore, PHD inhibitors have been the focus of recent studies on novel strategies to stabilize HIF. Cobalt is one of the inhibitors of PHD, and stimulation of HIF with cobalt is effective in a variety of kidney disease models. Furthermore, crystal structures of the catalytic domain of human prolyl hydroxylase 2 have been clarified recently. The structure aids in the design of PHD selective inhibitors for the treatment of hypoxic tissue injury. Current advance has elucidated the detailed mechanism of hypoxia-induced transcription, giving hope for the development of novel therapeutic approaches against hypoxia.

Review of Diagnostic and Therapeutic Approach to Canine Myxomatous Mitral Valve Disease

PubMed Central

Borgarelli, Michele

2017-01-01

The most common heart disease that affects dogs is myxomatous mitral valve disease. In this article, we review the current diagnostic and therapeutic approaches to this disease, and we also present some of the latest technological advancements in this field. PMID:29056705

Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

PubMed

Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

2018-03-01

Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Therapeutic gene targeting approaches for the treatment of dyslipidemias and atherosclerosis.

PubMed

Mäkinen, Petri I; Ylä-Herttuala, Seppo

2013-04-01

Despite improved therapies, cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, new therapeutic approaches are still needed. In the gene therapy field, RNA interference (RNAi) and regulation of microRNAs (miRNAs) have gained a lot of attention in addition to traditional overexpression based strategies. Here, recent findings in therapeutic gene silencing and modulation of small RNA expression related to atherogenesis and dyslipidemia are summarized. Novel gene therapy approaches for the treatment of hyperlipidemia have been addressed. Antisense oligonucleotide and RNAi-based therapies against apolipoprotein B100 and proprotein convertase subtilisin/kexin type 9 have shown already efficacy in preclinical and clinical trials. In addition, several miRNAs dysregulated in atherosclerotic lesions and regulating cholesterol homeostasis have been found, which may represent novel targets for future therapies. New therapies for lowering lipid levels are now being tested in clinical trials, and both antisense oligonucleotide and RNAi-based therapies have shown promising results in lowering cholesterol levels. However, the modulation of inflammatory component in atherosclerosis by gene therapy and targeting of the effects to plaques are still difficult challenges.

Systems biology approach to developing S(2)RM-based "systems therapeutics" and naturally induced pluripotent stem cells.

PubMed

Maguire, Greg; Friedman, Peter

2015-05-26

The degree to, and the mechanisms through, which stem cells are able to build, maintain, and heal the body have only recently begun to be understood. Much of the stem cell's power resides in the release of a multitude of molecules, called stem cell released molecules (SRM). A fundamentally new type of therapeutic, namely "systems therapeutic", can be realized by reverse engineering the mechanisms of the SRM processes. Recent data demonstrates that the composition of the SRM is different for each type of stem cell, as well as for different states of each cell type. Although systems biology has been successfully used to analyze multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. A new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called "systems therapeutics". A natural set of healing pathways in the human that uses SRM is instructive and of practical use in developing systems therapeutics. Endogenous SRM processes in the human body use a combination of SRM from two or more stem cell types, designated as S(2)RM, doing so under various state dependent conditions for each cell type. Here we describe our approach in using state-dependent SRM from two or more stem cell types, S(2)RM technology, to develop a new class of therapeutics called "systems therapeutics." Given the ubiquitous and powerful nature of innate S(2)RM-based healing in the human body, this "systems therapeutic" approach using S(2)RM technology will be important for the development of anti-cancer therapeutics, antimicrobials, wound care products and procedures, and a number of other therapeutics for many indications.

Approaches to Preventative and Therapeutic HIV vaccines

PubMed Central

Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

2016-01-01

Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies.

PubMed

Mueller, Alan J; Peffers, Mandy J; Proctor, Carole J; Clegg, Peter D

2017-08-01

Systems orientated research offers the possibility of identifying novel therapeutic targets and relevant diagnostic markers for complex diseases such as osteoarthritis. This review demonstrates that the osteoarthritis research community has been slow to incorporate systems orientated approaches into research studies, although a number of key studies reveal novel insights into the regulatory mechanisms that contribute both to joint tissue homeostasis and its dysfunction. The review introduces both top-down and bottom-up approaches employed in the study of osteoarthritis. A holistic and multiscale approach, where clinical measurements may predict dysregulation and progression of joint degeneration, should be a key objective in future research. The review concludes with suggestions for further research and emerging trends not least of which is the coupled development of diagnostic tests and therapeutics as part of a concerted effort by the osteoarthritis research community to meet clinical needs. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1573-1588, 2017. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

Affinity approaches in RNAi-based therapeutics purification.

PubMed

Pereira, Patrícia; Queiroz, João A; Figueiras, Ana; Sousa, Fani

2016-05-15

The recent investigation on RNA interference (RNAi) related mechanisms and applications led to an increased awareness of the importance of RNA in biology. Nowadays, RNAi-based technology has emerged as a potentially powerful tool for silencing gene expression, being exploited to develop new therapeutics for treating a vast number of human disease conditions, as it is expected that this technology can be translated onto clinical applications in a near future. This approach makes use of a large number of small (namely short interfering RNAs, microRNAs and PIWI-interacting RNAs) and long non-coding RNAs (ncRNAs), which are likely to have a crucial role as the next generation therapeutics. The commercial and biomedical interest in these RNAi-based therapy applications have fostered the need to develop innovative procedures to easily and efficiently purify RNA, aiming to obtain the final product with high purity degree, good quality and biological activity. Recently, affinity chromatography has been applied to ncRNAs purification, in view of the high specificity. Therefore, this article intends to review the biogenesis pathways of regulatory ncRNAs and also to discuss the most significant and recent developments as well as applications of affinity chromatography in the challenging task of purifying ncRNAs. In addition, the importance of affinity chromatography in ncRNAs purification is addressed and prospects for what is forthcoming are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy.

PubMed

Hosseini, Maryam; Haji-Fatahaliha, Mostafa; Jadidi-Niaragh, Farhad; Majidi, Jafar; Yousefi, Mehdi

2016-06-01

Cancer is one of the most important causes of death all over the world, which has not yet been treated efficiently. Although several therapeutic approaches have been used, some side effects such as toxicity and drug resistance have been observed in patients, particularly with chemotherapy. The nanoparticle-mediated drug delivery systems (DDS) have a great potential to improve cancer treatment by transferring therapeutic factors directly to the tumor site. Such a treatment significantly decreases the adverse effects associated with cancer therapy on healthy tissues. Two main strategies, including passive and active methods, have been considered to be effective techniques which can target the drugs to the tumor sites. The current review sheds some light on the place of nanotechnology in cancer drug delivery, and introduces nanomaterials and their specific characteristics that can be used in tumor therapy. Moreover, passive and active targeting approaches focus on antibodies, particularly single chain variable fragments (scFv), as a novel and important ligand in a drug delivery system.

Therapeutic approaches targeting intestinal microflora in inflammatory bowel disease

PubMed Central

Andoh, Akira; Fujiyama, Yoshihide

2006-01-01

Inflammatory bowel diseases, ulcerative colitis, and Crohn’s disease, are chronic intestinal disorders of unknown etiology in which in genetically susceptible individuals, the mucosal immune system shows an aberrant response towards commensal bacteria. The gastrointestinal tract has developed ingenious mechanisms to coexist with its autologous microflora, but rapidly responds to invading pathogens and then returns to homeostasis with its commensal bacteria after the pathogenic infection is cleared. In case of disruption of this tightly-regulated homeostasis, chronic intestinal inflammation may be induced. Previous studies showed that some commensal bacteria are detrimental while others have either no influence or have a protective action. In addition, each host has a genetically determined response to detrimental and protective bacterial species. These suggest that therapeutic manipulation of imbalance of microflora can influence health and disease. This review focuses on new insights into the role of commensal bacteria in gut health and disease, and presents recent findings in innate and adaptive immune interactions. Therapeutic approaches to modulate balance of intestinal microflora and their potential mechanisms of action are also discussed. PMID:16874854

Integrated Artificial Intelligence Approaches for Disease Diagnostics.

PubMed

Vashistha, Rajat; Chhabra, Deepak; Shukla, Pratyoosh

2018-06-01

Mechanocomputational techniques in conjunction with artificial intelligence (AI) are revolutionizing the interpretations of the crucial information from the medical data and converting it into optimized and organized information for diagnostics. It is possible due to valuable perfection in artificial intelligence, computer aided diagnostics, virtual assistant, robotic surgery, augmented reality and genome editing (based on AI) technologies. Such techniques are serving as the products for diagnosing emerging microbial or non microbial diseases. This article represents a combinatory approach of using such approaches and providing therapeutic solutions towards utilizing these techniques in disease diagnostics.

Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

PubMed Central

Kurtoğlu, Selim; Özdemir, Ahmet

2017-01-01

Fetal and neonatal hyperthyroidism may occur in mothers with Graves’ disease. Fetal thyrotoxicosis manifestation is observed with the transition of TSH receptor stimulating antibodies to the fetus from the 17th–20th weeks of pregnancy and with the fetal TSH receptors becoming responsive after 20 weeks. The diagnosis is confirmed by fetal tachycardia, goiter and bone age advancement in pregnancy and maternal treatment is conducted in accordance. The probability of neonatal hyperthyroidism is high in the babies of mothers that have ongoing antithyroid requirement and higher antibody levels in the last months of pregnancy. Clinical manifestation may be delayed by 7–17 days because of the antithyroid drugs taken by the mother. Neonatal hyperthyroidism symptoms can be confused with sepsis and congenital viral infections. Herein, the diagnosis and therapeutic approach are reviewed in cases of fetal neonatal hyperthyroidism. PMID:28439194

Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction

PubMed Central

Xin, Zhong-Cheng; Xu, Yong-De; Lin, Guiting; Lue, Tom F; Guo, Ying-Lu

2016-01-01

Transplanted stem cells (SCs), owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED). However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1) SC niche and SC biological features in vitro; (2) localization and mobilization of endogenous SCs; (3) existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED. PMID:25926601

Genome Editing: A New Approach to Human Therapeutics.

PubMed

Porteus, Matthew

2016-01-01

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

PubMed Central

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

2014-01-01

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

Exploring miRNA based approaches in cancer diagnostics and therapeutics.

PubMed

Mishra, Shivangi; Yadav, Tanuja; Rani, Vibha

2016-02-01

MicroRNAs (miRNAs), a highly conserved class of tissue specific, small non-protein coding RNAs maintain cell homeostasis by negative gene regulation. Proper controlling of miRNA expression is required for a balanced physiological environment, as these small molecules influence almost every genetic pathway from cell cycle checkpoint, cell proliferation to apoptosis, with a wide range of target genes. Deregulation in miRNAs expression correlates with various cancers by acting as tumor suppressors and oncogenes. Although promising therapies exist to control tumor development and progression, there is a lack of efficient diagnostic and therapeutic approaches for delineating various types of cancer. The molecularly different tumors can be differentiated by specific miRNA profiling as their phenotypic signatures, which can hence be exploited to surmount the diagnostic and therapeutic challenges. Present review discusses the involvement of miRNAs in oncogenesis with the analysis of patented research available on miRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.

PubMed

Bonafede, Roberta; Mariotti, Raffaella

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.

The management of a sexually charged clinical problem: social structural and psychoanalytic functionalist approaches in a therapeutic community.

PubMed

James, O W

1986-03-01

An event in a therapeutic community is examined from the perspectives of the structuralism of Durkheim and the functionalism of psychoanalysis. Although these two approaches might appear theoretically contradictory, analysis of the evidence shows them to be clinically complementary. The role of social structure in therapeutic communities requires deliberate conceptualization if such communities are to be demonstrably therapeutic.

Recent Progress in Nanomedicine: Therapeutic, Diagnostic and Theranostic Applications

PubMed Central

Rizzo, Larissa Y.; Theek, Benjamin; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2013-01-01

In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-) physiological processes. In addition, ever more efforts have been undertaken to combine diagnostic and therapeutic properties within a single nanomedicine formulation. These so-called nanotheranostics are able to provide valuable information on drug delivery, drug release and drug efficacy, and they are considered to be highly useful for personalizing nanomedicine-based (chemo-) therapeutic interventions. PMID:23578464

New therapeutic approaches to spinal muscular atrophy.

PubMed

Lewelt, Aga; Newcomb, Tara M; Swoboda, Kathryn J

2012-02-01

Bench to bedside progress has been widely anticipated for a growing number of neurodegenerative disorders. Of these, spinal muscular atrophy (SMA) is perhaps the best poised to capitalize on advances in targeted therapeutics development over the next few years. Several laboratories have achieved compelling success in SMA animal models using sophisticated methods for targeted delivery, repair, or increased expression of the survival motor neuron protein, SMN. The clinical community is actively collaborating to identify, develop, and validate outcome measures and biomarkers in parallel with laboratory efforts. Innovative trial design and synergistic approaches to maximize proactive care in conjunction with treatment with one or more of the promising pharmacologic and biologic therapies currently in the pipeline will maximize our chances to achieve meaningful outcomes for patients. This review highlights recent promising scientific and clinical advances bringing us ever closer to effective treatment(s) for our patients with SMA.

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

PubMed Central

Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Espigado, Ildefonso; Ruiz Pérez de Pipaon, Maite; Falantes, José; de la Cruz, Fátima; Cisneros, José M.

2012-01-01

Background Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients’ risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and Methods This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Results Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Conclusions Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients

Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

PubMed

Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

2007-01-01

The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2014-10-01

AD_________________ Award Number: W81XWH-13-1-0325 TITLE: Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using ...Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING ORGANIZATION ...Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER W81XWH-13-1-0325 Carcinoma Using Genetically Engineered Mouse Models and 5b

The third international meeting on genetic disorders in the RAS/MAPK pathway: towards a therapeutic approach.

PubMed

Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D; Gripp, Karen W; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo; MacRae, Calum A; Messiaen, Ludwine; Mulero-Navarro, Sonia; Neel, Benjamin; Plotkin, Scott; Rauen, Katherine A; Roberts, Amy; Silva, Alcino J; Sittampalam, Sitta G; Zhang, Chao; Schoyer, Lisa

2015-08-01

"The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. © 2015 Wiley Periodicals, Inc.

A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

ERIC Educational Resources Information Center

Williams, Todd O.

2012-01-01

A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

Therapeutic approaches for portal biliopathy: A systematic review

PubMed Central

Franceschet, Irene; Zanetto, Alberto; Ferrarese, Alberto; Burra, Patrizia; Senzolo, Marco

2016-01-01

Portal biliopathy (PB) is defined as the presence of biliary abnormalities in patients with non-cirrhotic/non-neoplastic extrahepatic portal vein obstruction (EHPVO) and portal cavernoma (PC). The pathogenesis of PB is due to ab extrinseco compression of bile ducts by PC and/or to ischemic damage secondary to an altered biliary vascularization in EHPVO and PC. Although asymptomatic biliary abnormalities can be frequently seen by magnetic resonance cholangiopancreatography in patients with PC (77%-100%), only a part of these (5%-38%) are symptomatic. Clinical presentation includes jaundice, cholangitis, cholecystitis, abdominal pain, and cholelithiasis. In this subset of patients is required a specific treatment. Different therapeutic approaches aimed to diminish portal hypertension and treat biliary strictures are available. In order to decompress PC, surgical porto-systemic shunt or transjugular intrahepatic porto-systemic shunt can be performed, and treatment on the biliary stenosis includes endoscopic (Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy, balloon dilation, stone extraction, stent placement) and surgical (bilioenteric anastomosis, cholecystectomy) approaches. Definitive treatment of PB often requires multiple and combined interventions both on vascular and biliary system. Liver transplantation can be considered in patients with secondary biliary cirrhosis, recurrent cholangitis or unsuccessful control of portal hypertension. PMID:28018098

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

PubMed Central

Sahu, Praveen K.; Satpathi, Sanghamitra; Behera, Prativa K.; Mishra, Saroj K.; Mohanty, Sanjib; Wassmer, Samuel Crocodile

2015-01-01

Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively. PMID:26579500

Gummy smile: clinical parameters useful for diagnosis and therapeutical approach.

PubMed

Monaco, Annalisa; Streni, Oriana; Marci, Maria Chiara; Marzo, Giuseppe; Gatto, Roberto; Giannoni, Mario

2004-01-01

In the analysis of the characteristics of a pleasant smile, a gummy smile has negative components, which most affect the esthetics of non-verbal communication. For this purpose a proposed classification based upon etiopathogenetic criteria as useful indications for a therapeutical approach is given. The nature of a high smile line can be: dento-gingival, connected to an abnormal dental eruption, which is revealed by a short clinic crown; muscular, caused by an hyperactivity of the elevator muscle of the upper lip; dento-alveolar (skeletal), due to an excessive protuberance or vertical growth of the jawbone (maxillary); lastly, a mixed nature, in the presence of more than one of the above described factors The diagnosis of gummy smile must be precocious and based, with reference to specific parameters, upon a careful analysis of the etiopathogenetic factors and the degree of seriousness of the alteration. A correct treatment plan must contemplate the possibility of an orthognatodontic, orthopedic and/or surgical therapeutic resolution considering the seriousness and complexity of the gums exposures (high smile line) in connection with the age of the subject.

Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment.

PubMed

Atkinson, Stuart P; Andreu, Zoraida; Vicent, María J

2018-01-23

Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies. We discuss the various "hurdles" that a given PT faces on its passage from the syringe to the tumor (and beyond), including the passage through the bloodstream, tumor targeting, tumor uptake and the intracellular release of the active agent. However, we also discuss other relevant concepts and new considerations in the field, which we hope will provide new insight into the possible applications of PT-related biomarkers.

Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment

PubMed Central

Atkinson, Stuart P.; Andreu, Zoraida; Vicent, María J.

2018-01-01

Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies. We discuss the various “hurdles” that a given PT faces on its passage from the syringe to the tumor (and beyond), including the passage through the bloodstream, tumor targeting, tumor uptake and the intracellular release of the active agent. However, we also discuss other relevant concepts and new considerations in the field, which we hope will provide new insight into the possible applications of PT-related biomarkers. PMID:29360800

Giant pituitary adenoma: histological types, clinical features and therapeutic approaches.

PubMed

Iglesias, Pedro; Rodríguez Berrocal, Víctor; Díez, Juan José

2018-06-16

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches?

PubMed

Phillip, Harris; Okewole, Idris; Chilaka, Victor

2014-06-01

Urethral pain syndrome has had several sobriquets, which have led to much confusion over the existence of this pathological condition and the useful options in the care of the afflicted patient. Our aim was to explore the proposed etiologies of this syndrome, and to provide a critical analysis of each proposed etiology and present a balanced argument on the plausibility of the proposed etiology and therapeutic approaches. We carried out an English language electronic search in the following databases: Medline, Embase, Amed, Cinahl, Pubmed, Cochrane Library, Trip Database and SUMSearch using the following search terms: urethral syndrome, urethral diseases, urethra, urologic diseases etiology/etiology, presentation, treatment, outcome, therapeutics and treatment from 1951 to 2011. In excess of 200 articles were recovered. With the clearly defined objectives of analyzing the proposed etiologies and therapeutic regimes, two author(s) (HP and IO) perused the abstracts of all the recovered articles, selecting those that addressed the etiologies and therapeutic approaches to treating the urethral pain syndrome. The number of articles was reduced to 25. The full text of all 25 articles were retrieved and reviewed. Through the present article, we hope to elucidate the most probable etiology of this condition whilst simultaneously, advance a logical explanation for the apparent success in the treatment of this condition using a range of different therapeutic modalities. We have carried out a narrative review, which we hope will reduce some of the confusion around this clinical entity by combining the known facts about the disease. © 2014 The Japanese Urological Association.

Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy

PubMed Central

Tisdale, Sarah

2015-01-01

Motor neuron diseases are neurological disorders characterized primarily by the degeneration of spinal motor neurons, skeletal muscle atrophy, and debilitating and often fatal motor dysfunction. Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease of high incidence and severity and the most common genetic cause of infant mortality. SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene and retention of at least one copy of the hypomorphic gene paralog SMN2. Early studies established a loss-of-function disease mechanism involving ubiquitous SMN deficiency and suggested SMN upregulation as a possible therapeutic approach. In recent years, greater knowledge of the central role of SMN in RNA processing combined with deep characterization of animal models of SMA has significantly advanced our understanding of the cellular and molecular basis of the disease. SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types. Advances in SMA research have also led to the development of several potential therapeutics shown to be effective in animal models of SMA that are now in clinical trials. These agents offer unprecedented promise for the treatment of this still incurable neurodegenerative disease. PMID:26063904

[Therapeutic approaches in autism spectrum disorders].

PubMed

Ruggieri, Víctor L; Arberas, Claudia L

2015-02-25

Autistic spectrum disorders affect one out of every 68 persons, with a 4:1 dominance in males. Since they are dysfunctions rather than irreversible injuries to the central nervous system, which can be attributed to deficits in the neuronal networks and synaptogenesis and are modifiable thanks to the plasticity of the brain, starting therapy as early as possible is essential for more favourable progress. Very few treatments are backed by solid scientific evidence. We will analyse the therapeutic approaches oriented towards improving autism spectrum disorders which showed a clinical improvement that can be related to neurophysiological or functional changes in the central nervous system. We will classify the behavioural educational treatments and those in the research phase into a hierarchy, highlighting the neurogenetic entities with a high prevalence of autism, in which their pathophysiology and molecular base are known, that attempt to modify the consequences of those alterations by means of pharmacological agents. These entities include fragile X syndrome (GABAergic and metabotropic glutamate receptor inhibitors), tuberous sclerosis (mTOR inhibitors), Phelan-McDermid syndrome and Rett syndrome (insulin-like growth factor 1 inhibitors). Oxytocin, which has been shown to improve social cognition in persons with autism spectrum disorders, is analysed separately.

Strategies for transformation of naturally-occurring amphibian antimicrobial peptides into therapeutically valuable anti-infective agents.

PubMed

Conlon, J Michael; Al-Ghaferi, Nadia; Abraham, Bency; Leprince, Jérôme

2007-08-01

The emergence of strains of pathogenic microorganisms with resistance to commonly used antibiotics has necessitated a search for novel types of antimicrobial agents. Many frog species produce amphipathic alpha-helical peptides with broad spectrum antimicrobial activity in the skin but their therapeutic potential is limited by varying degrees of cytolytic activity towards eukaryotic cells. Methods for development of such peptides into anti-infective drugs are illustrated by the example of temporin-1DRa (HFLGTLVNLAK KIL.NH(2)). Studies with model alpha-helical peptides have shown that increase in cationicity promotes antimicrobial activity whereas increases in hydrophobicity, helicity and amphipathicity promote hemolytic activity and loss of selectivity for microorganisms. Analogs of temporin-1DRa in which each amino acid is replaced by L-lysine and D-lysine were synthesized and their cytolytic activities tested against a range of microorganisms and human erythrocytes. Small changes in structure produced marked changes in conformation, as determined by retention time on reversed-phase HPLC, and in biological activity. However, peptides containing the substitutions (Val(7) -->L-Lys), (Thr(5)-->D-Lys) and (Asn(8)-->D-Lys) retained the high solubility and potent, broad spectrum antimicrobial activity of the naturally occurring peptide but were appreciably (up to 10-fold) less hemolytic. In contrast, analogs in which Leu(9) and Ile(13) were replaced by the more hydrophobic cyclohexylglycine residue showed slightly increased antimicrobial potencies (up to 2-fold) but a 4-fold increase in hemolytic activity. The data suggest a strategy of selective increases in cationicity concomitant with decreases in helicity and hydrophobicity in the transformation of naturally-occurring antimicrobial peptides into non-toxic therapeutic agents.

A cool approach to reducing electrode-induced trauma: Localized therapeutic hypothermia conserves residual hearing in cochlear implantation.

PubMed

Tamames, Ilmar; King, Curtis; Bas, Esperanza; Dietrich, W Dalton; Telischi, Fred; Rajguru, Suhrud M

2016-09-01

The trauma caused during cochlear implant insertion can lead to cell death and a loss of residual hair cells in the cochlea. Various therapeutic approaches have been studied to prevent cochlear implant-induced residual hearing loss with limited success. In the present study, we show the efficacy of mild to moderate therapeutic hypothermia of 4 to 6 °C applied to the cochlea in reducing residual hearing loss associated with the electrode insertion trauma. Rats were randomly distributed in three groups: control contralateral cochleae, normothermic implanted cochleae and hypothermic implanted cochleae. Localized hypothermia was delivered to the middle turn of the cochlea for 20 min before and after implantation using a custom-designed probe perfused with cooled fluorocarbon. Auditory brainstem responses (ABRs) were recorded to assess the hearing function prior to and post-cochlear implantation at various time points up to 30 days. At the conclusion of the trials, inner ears were harvested for histology and cell count. The approach was extended to cadaver temporal bones to study the potential surgical approach and efficacy of our device. In this case, the hypothermia probe was placed next to the round window niche via the facial recess or a myringotomy. A significant loss of residual hearing was observed in the normothermic implant group. Comparatively, the residual hearing in the cochleae receiving therapeutic hypothermia was significantly conserved. Histology confirmed a significant loss of outer hair cells in normothermic cochleae receiving the surgical trauma when compared to the hypothermia treated group. In human temporal bones, a controlled and effective cooling of the cochlea was achieved using our approach. Collectively, these results suggest that therapeutic hypothermia during cochlear implantation may reduce traumatic effects of electrode insertion and improve conservation of residual hearing. Copyright © 2016 The Authors. Published by Elsevier B.V. All

Inflammatory Bowel Disease: Pathophysiology and Current Therapeutic Approaches.

PubMed

Abraham, Bincy P; Ahmed, Tasneem; Ali, Tauseef

2017-01-01

Inflammatory bowel diseases, most commonly categorized as Crohn's disease and ulcerative colitis, are immune mediated chronic inflammatory disorders of the gastrointestinal tract. The etiopathogenesis is multifactorial with different environmental, genetic, immune mediated, and gut microbial factors playing important role. The current goals of therapy are to improve clinical symptoms, control inflammation, prevent complications, and improve quality of life. Different therapeutic agents, with their indications, mechanisms of action, and side effects are discussed in this chapter. Anti-integrin therapy, a newer therapeutic class, with its potential beneficial role in both Crohn's disease and ulcerative colitis is also mentioned. In the end, therapeutic algorithms for both diseases are reviewed.

Immunopathogenesis and Therapeutic Approaches in Pediatric Celiac Disease

PubMed Central

Agarwal, Shreya; Kovilam, Oormila; Zach, Terence L.; Agrawal, Devendra K.

2016-01-01

Summary Celiac Disease is an autoimmune enteropathy with increasing incidence worldwide in both adults and children. It occurs as an inflammatory condition with destruction of the normal architecture of villi on consumption of gluten and related protein products found in wheat, barley and rye. However, the exact pathogenesis is not yet fully understood. A gluten-free diet remains the main modality of therapy to date. While some patients continue to have symptoms even on a gluten-free diet, adherence to this diet is also difficult, especially for the children. Hence, there is continued interest in novel methods of therapy and the current research focus is on the promising novel non-dietary modalities of treatment. Here, we critically reviewed the existing literature regarding the pathogenesis of celiac disease in children including the role of in-utero exposure leading to neonatal and infant sensitization and its application for the development of new therapeutic approaches for these patients. PMID:26999328

Biological and therapeutic properties of bee pollen: a review.

PubMed

Denisow, Bożena; Denisow-Pietrzyk, Marta

2016-10-01

Natural products, including bee products, are particularly appreciated by consumers and are used for therapeutic purposes as alternative drugs. However, it is not known whether treatments with bee products are safe and how to minimise the health risks of such products. Among others, bee pollen is a natural honeybee product promoted as a valuable source of nourishing substances and energy. The health-enhancing value of bee pollen is expected due to the wide range of secondary plant metabolites (tocopherol, niacin, thiamine, biotin and folic acid, polyphenols, carotenoid pigments, phytosterols), besides enzymes and co-enzymes, contained in bee pollen. The promising reports on the antioxidant, anti-inflammatory, anticariogenic antibacterial, antifungicidal, hepatoprotective, anti-atherosclerotic, immune enhancing potential require long-term and large cohort clinical studies. The main difficulty in the application of bee pollen in modern phytomedicine is related to the wide species-specific variation in its composition. Therefore, the variations may differently contribute to bee-pollen properties and biological activity and thus in therapeutic effects. In principle, we can unequivocally recommend bee pollen as a valuable dietary supplement. Although the bee-pollen components have potential bioactive and therapeutic properties, extensive research is required before bee pollen can be used in therapy. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Therapeutic approaches against common structural features of toxic oligomers shared by multiple amyloidogenic proteins.

PubMed

Guerrero-Muñoz, Marcos J; Castillo-Carranza, Diana L; Kayed, Rakez

2014-04-15

Impaired proteostasis is one of the main features of all amyloid diseases, which are associated with the formation of insoluble aggregates from amyloidogenic proteins. The aggregation process can be caused by overproduction or poor clearance of these proteins. However, numerous reports suggest that amyloid oligomers are the most toxic species, rather than insoluble fibrillar material, in Alzheimer's, Parkinson's, and Prion diseases, among others. Although the exact protein that aggregates varies between amyloid disorders, they all share common structural features that can be used as therapeutic targets. In this review, we focus on therapeutic approaches against shared features of toxic oligomeric structures and future directions. Copyright © 2014 Elsevier Inc. All rights reserved.

Constipation: Pathophysiology and Current Therapeutic Approaches.

PubMed

Sharma, Amol; Rao, Satish

2017-01-01

Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the

Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair

PubMed Central

Knott, Eric P.; Assi, Mazen; Rao, Sudheendra N. R.; Ghosh, Mousumi; Pearse, Damien D.

2017-01-01

A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies. The only known negative regulators of cyclic nucleotides are a family of enzymes called phosphodiesterases (PDEs) that hydrolyze cyclic nucleotides into adenosine monophosphate (AMP) or guanylate monophosphate (GMP). Herein, we discuss the structure and physiological function as well as the roles PDEs play in pathological processes of the diseased or injured CNS. Further we review the approaches that have been employed therapeutically in experimental paradigms to block PDE expression or activity and in turn elevate cyclic nucleotide levels to mediate neuroprotection or neurorepair as well as discuss both the translational pathway and current limitations in moving new PDE-targeted therapies to the clinic. PMID:28338622

Valuable water

NASA Astrophysics Data System (ADS)

Carlowicz, Michael

In some places, money flows with water. Studying both the water quality and property values around 22 lakes in south-central Maine, Kevin Boyle and Holly James of the University of Maine and Roy Bouchard of the Maine Department of Environmental Protection have found that good water quality makes waterfront property even more valuable. To gauge water quality, the researchers used Secchi disks to measure the clarity of the water at depth. They also reviewed 543 lakefront property sales between 1990 and 1994 to determine how values correlated with changing water conditions. The group also considered such factors as lake frontage, sizes of the houses and lots, and size of the lake.

Integrative Therapeutic Approaches for the Management and Control of Nausea in Children Undergoing Cancer Treatment: A Systematic Review of Literature.

PubMed

Momani, Tha'er G; Berry, Donna L

Chemotherapy-induced nausea and vomiting (CINV) continues to be a common symptom experienced by children undergoing cancer treatment despite the use of contemporary antiemetics. Integrative therapeutic approaches in addition to standard pharmacologic antiemetic regimes offer potential to control CINV. The purpose of this review was to identify current evidence on integrative therapeutic approaches for the control of CINV in children with cancer. Online search engines (PubMed, CINAHL, PsychINFO) were queried using MESH terms. Titles, abstracts, and then full-text articles were reviewed for relevance to the review. The search resulted in 53 studies. Twenty-one studies met our review criteria. Integrative therapies identified included acupuncture/acupressure, aromatherapy, herbal supplements, hypnosis, and other cognitive behavioral interventions. Our review identified little information on the effectiveness and safety of most integrative therapeutic approaches for the control and management of CINV in children with cancer. However, evidence from adult cancer studies and some pediatric studies identify promising interventions for further testing.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases.

PubMed

Halilbasic, Emina; Steinacher, Daniel; Trauner, Michael

2017-01-01

Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on "Bile Acids in Health and Disease" held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC. © 2017 S. Karger AG, Basel.

Toxin-Based Therapeutic Approaches

PubMed Central

Shapira, Assaf; Benhar, Itai

2010-01-01

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

THERAPEUTIC APPROACH AND ITS RELATIONSHIP WITH SOCIAL AND ECONOMIC CHARACTERISTICS OF USERS OF CENTERS FOR PSYCHOSOCIAL CARE FOR CHILDREN AND ADOLESCENTS

PubMed Central

Gondim, Ana Paula Soares; Maciel, Ana Paula Pessoa; Monteiro, Mirian Parente

2017-01-01

ABSTRACT Objective: To analyze the therapeutic approach and its relationship with the economic and social characteristics and the care of children in Centers for Psychosocial Attention. Methods: Descriptive study with a sample of 294 children monitored in two Centers for Psychosocial Attention to Children and Adolescents in Fortaleza, Ceará, Northeast Brazil. The study was conducted from February to December, 2012. Participants were accompanied by their parents or caregivers. Data were collected in a structured questionnaire containing social, economic and care variables. The bivariate analysis used the χ2 test to test the association between variables. Results: In this study, 292 children aged 3-12 were selected, following the order of attendance at the service, most of them male (74.3%) and belonging to social classes D and E (89.3%). The most frequent diagnosis referred to by the caregivers was mental disorders. Three different therapeutic approaches were identified: pharmacological approach (44.5%); non-pharmacological approach (11.6%); association of both techniques (43.8%). For all therapeutic approaches, there was association with the variable living situation (p=0.021), as well as with the variables, “improving” with the treatment (p=0.002) and “problems” with the treatment (p=0,004). Conclusions: It was possible to highlight that the associated therapeutic approach (pharmacological and non-pharmacological treatment) provides more benefits to children. Therefore, associating the medicines to the psychotherapeutic practices may be recommended as a strategy in the mental health policy directed to children and adolescents. PMID:29185621

Educating Tomorrow's Valuable Citizen.

ERIC Educational Resources Information Center

Burstyn, Joan N., Ed.

This collection of essays by various authors discusses the dilemmas that face those who would educate tomorrow's valuable citizens and describes the day-to-day commitment needed to maintain a community. The book gives guidelines for action through examples of current programs that provide a forum for civic discussion and public consensus on the…

[Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

PubMed

Tsuji, Daisuke

2013-01-01

Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice.

Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

PubMed Central

Sortino, Maria A.; Salomone, Salvatore; Carruba, Michele O.; Drago, Filippo

2017-01-01

Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios. PMID:28642705

Genetic therapeutic approaches for Duchenne muscular dystrophy.

PubMed

Foster, Helen; Popplewell, Linda; Dickson, George

2012-07-01

Despite an expansive wealth of research following the discovery of the DMD gene 25 years ago, there is still no curative treatment for Duchenne muscular dystrophy. However, there are currently many promising lines of research, including cell-based therapies and pharmacological reagents to upregulate dystrophin via readthrough of nonsense mutations or by upregulation of the dystrophin homolog utrophin. Here we review genetic-based therapeutic strategies aimed at the amelioration of the DMD phenotype. These include the reintroduction of a copy of the DMD gene into an affected tissue by means of a viral vector; correction of the mutated DMD transcript by antisense oligonucleotide-induced exon skipping to restore the open reading frame; and direct modification of the DMD gene at a chromosomal level through genome editing. All these approaches are discussed in terms of the more recent advances, and the hurdles to be overcome if a comprehensive and effective treatment for DMD is to be found. These hurdles include the need to target all musculature of the body. Therefore any potential treatment would need to be administered systemically. In addition, any treatment needs to have a long-term effect, with the possibility of readministration, while avoiding any potentially detrimental immune response to the vector or transgene.

The Singapore approach to human stem cell research, therapeutic and reproductive cloning.

PubMed

Kian, Catherine Tay Swee; Leng, Tien Sim

2005-06-01

With the controversial ethical issues on the creation of human embryos through cloning for therapeutic research, which holds more promise of medical breakthroughs that the world could ever imagine and the acknowledgement by many scientists that this technology may not lead in the near future to therapies; this country report discusses the approach Singapore takes on human stem cell research, interjected with the authors' own arguments and suggestions especially on research compensation injuries, an often neglected important issue. International comparative viewpoints taken by the major countries in the world are also included in the appendix.

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

PubMed

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.

Control of Bovine Mastitis: Old and Recent Therapeutic Approaches.

PubMed

Gomes, Fernanda; Henriques, Mariana

2016-04-01

Mastitis is defined as the inflammatory response resulting of the infection of the udder tissue and it is reported in numerous species, namely in domestic dairy animals. This pathology is the most frequent disease of dairy cattle and can be potentially fatal. Mastitis is an economically important pathology associated with reduced milk production, changes in milk composition and quality, being considered one of the most costly to dairy industry. Therefore, the majority of research in the field has focused on control of bovine mastitis and many efforts are being made for the development of new and effective anti-mastitis drugs. Antibiotic treatment is an established component of mastitis control programs; however, the continuous search for new therapeutic alternatives, effective in the control and treatment of bovine mastitis, is urgent. This review will provide an overview of some conventional and emerging approaches in the management of bovine mastitis' infections.

Dietary and body weight control: therapeutic education, motivational interviewing and cognitive-behavioral approaches for long-term weight loss maintenance.

PubMed

Golay, Alain

2006-01-01

A diet always induces weight loss in the short term. The loss does not depend on the dietary composition but rather on the caloric deficit. However, a drastic diet often induces binge eating disorders and can lead to a weight gain in the long term. A cognitive-behavioral-nutritional approach allows lasting weight loss and best results with low fat diets in the long term. Therapeutic education is a patient-centered humanistic approach which allows patients to be actors in their own treatment and own diet to improve their success in losing weight and their quality of life. Motivational interviewing and cognitive-behavioral approaches are perfect complements to therapeutic education for long-term weight loss maintenance. Finally, the best diet is the one that the patient can follow in the long term.

New therapeutic approaches for management of sport-induced muscle strains.

PubMed

De Carli, Angelo; Volpi, Piero; Pelosini, Iva; Ferretti, Andrea; Melegati, Gianluca; Mossa, Luigi; Tornese, Davide; de Girolamo, Laura; Scarpignato, Carmelo

2009-12-01

Muscle strains are one of the most common sports-induced injuries. Depending on the severity and location of the muscle strain, different treatment approaches can be taken. This review highlights recent trends in conservative, pharmacologic, and surgical approaches to the management of sports-induced muscle injuries as presented at a symposium held during the 93rd Annual Congress of the Italian Society of Orthopedics and Traumatology (SIOT) in Rome, Italy in November 2008. Conservative approaches now include growth factor therapy and administration of autologous platelet-rich plasma during the early postinjury period; however, its use is currently considered a doping violation under the World Anti-Doping Agency code, therefore restricting its use to nonelite sports people only. Topical anti-inflammatory therapy is a promising therapeutic strategy, since it allows local analgesic and anti-inflammatory effects while minimizing systemic adverse events. As the drug delivery system is critical to clinical effectiveness, the advent of a new delivery system for ketoprofen via a new-generation plaster with a marked increase in tissue penetration and a clinical efficacy comparable with that of oral administration, provides a viable option in the treatment of single sport lesions. Surgical treatment of muscle lesions is less common than conservative and topical therapies and indications are limited to more serious injuries. Presentations from SIOT 2008 show that advances in our understanding of the healing process and in conservative, pharmacologic, and surgical treatment approaches to the management of sports-induced muscle strains contribute to better clinical outcomes, faster healing, and a swifter return to normal training and activity levels.

Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases.

PubMed

Keeling, Kim M; Bedwell, David M

2011-01-01

Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy. Copyright © 2011 John Wiley & Sons, Ltd.

Mind-mapping for lung cancer: Towards a personalized therapeutics approach

PubMed Central

Mollberg, N; Surati, M; Demchuk, C; Fathi, R; Salama, AK; Husain, AN; Hensing, T; Salgia, R

2011-01-01

There will be over 220,000 people diagnosed with lung cancer and over 160,000 dying of lung cancer this year alone in the United States. In order to arrive at better control, prevention, diagnosis, and therapeutics for lung cancer, we must be able to personalize the approach towards lung cancer. Mind-mapping has existed for centuries for physicians to properly think about various “flows” of personalized medicine. We include here the epidemiology, diagnosis, histology, and treatment of lung cancer—specifically, non-small cell lung cancer. As we have new molecular signatures for lung cancer, this is further detailed. This review is not meant to be a comprehensive review, but rather its purpose is to highlight important aspects of lung cancer diagnosis, management, and personalized treatment options. PMID:21337123

Neoplastic Meningitis from Solid Tumors: New Diagnostic and Therapeutic Approaches

PubMed Central

Zustovich, Fable; Farina, Patrizia; Della Puppa, Alessandro; Manara, Renzo; Cecchin, Diego; Brunello, Antonella; Cappetta, Alessandro; Zagonel, Vittorina

2011-01-01

Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. PMID:21795431

Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update.

PubMed

Tiwari, Pragya

2015-01-01

Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management.

Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update

PubMed Central

Tiwari, Pragya

2015-01-01

Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management. PMID:26273667

Development of novel cardiovascular therapeutics from small regulatory RNA molecules--an outline of key requirements.

PubMed

Poller, W; Fechner, H

2010-01-01

Understanding of the roles of RNAs within the cell has changed and expanded dramatically during the past few years. Based on fundamentally new insights it is now increasingly possible to employ RNAs as highly valuable tools in molecular biology and medicine. At present, the most important therapeutic strategies are based on non-coding regulatory RNAs inducing RNA interference (RNAi) to silence single genes, and on modulation of cellular microRNAs (miRNAs) to alter complex gene expression patterns in diseased organs. Only recently it became possible to target therapeutic RNAi to specific organs via organotropic viral vector systems and we discuss the most recent strategies in this field, e.g. heart failure treatment by cardiac-targeted RNAi. Due to the peculiar biochemical properties of small RNA molecules, true therapeutic translation of results in vitro is more demanding than with small molecule drugs or proteins. Specifically, there is a critical requirement for extensive studies in animal models of human disease after pre-testing of the RNAi tools in vitro. This requirement likewise applies for miRNA modulations which have complex consequences in the recipient dependent on biochemical stability and distribution of the therapeutic RNA. Problems not yet fully solved are the prediction of targets and specificity of the RNA tools. However, major progress has been made to achieve their tissue-specific and regulatable expression, and breakthroughs in vector technologies from the gene therapy field have fundamentally improved safety and efficacy of RNA-based therapeutic approaches, too. In summary, insight into the molecular mechanisms of action of regulatory RNAs in combination with new delivery tools for RNA therapeutics will significantly expand our cardiovascular therapeutic repertoire beyond classical pharmacology.

A Person-Centered Counseling Approach as a Primary Therapeutic Support for Women with a History of Childhood Sexual Abuse

ERIC Educational Resources Information Center

Edwards, Nivischi N.; Lambie, Glenn W.

2009-01-01

Childhood sexual abuse (CSA) is prevalent among women. Person-centered counseling (PCC) is an effective core therapeutic approach to use when treating women with this issue. This article provides (a) an overview of CSA, (b) an orientation to PCC, and (c) a case example illustrating the primary application of this approach.

Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer.

PubMed

Chang, Hae Ryung; Nam, Seungyoon; Lee, Jinhyuk; Kim, Jin-Hee; Jung, Hae Rim; Park, Hee Seo; Park, Sungjin; Ahn, Young Zoo; Huh, Iksoo; Balch, Curt; Ku, Ja-Lok; Powis, Garth; Park, Taesung; Jeong, Jin-Hyun; Kim, Yon Hui

2016-12-06

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors. To develop evidence-based precision medicine for heterogeneous cancers, we established a systematic approach to integrate transcriptomic and genomic data. Predicted signaling subpathways were then laboratory-validated both in vitro and in vivo, resulting in the identification of new candidate therapeutic targets. Here, we show: i) differences in RHOA expression patterns, and its pathway activity, between Asian and Caucasian GC tumors; ii) in vitro and in vivo perturbed RHOA expression inhibits GC cell growth in high RHOA-expressing cell lines; iii) inverse correlation between RHOA and RHOB expression; and iv) an innovative small molecule design strategy for RHOA inhibitors. In summary, RHOA, and its oncogenic signaling pathway, represent a strong biomarker-driven therapeutic target for Asian GC. This comprehensive strategy represents a promising approach for the development of "hit" compounds.

A revised approach for an exact analytical solution for thermal response in biological tissues significant in therapeutic treatments.

PubMed

Dutta, Jaideep; Kundu, Balaram

2017-05-01

The genesis of the present research paper is to develop a revised exact analytical solution of thermal profile of 1-D Pennes' bioheat equation (PBHE) for living tissues influenced in thermal therapeutic treatments. In order to illustrate the temperature distribution in living tissue both Fourier and non-Fourier model of 1-D PBHE has been solved by 'Separation of variables' technique. Till date most of the research works have been carried out with the constant initial steady temperature of tissue which is not at all relevant for the biological body due to its nonhomogeneous living cells. There should be a temperature variation in the body before the therapeutic treatment. Therefore, a coupled heat transfer in skin surface before therapeutic heating must be taken account for establishment of exact temperature propagation. This approach has not yet been considered in any research work. In this work, an initial condition for solving governing differential equation of heat conduction in biological tissues has been represented as a function of spatial coordinate. In a few research work, initial temperature distribution with PBHE has been coupled in such a way that it eliminates metabolic heat generation. The study has been devoted to establish the comparison of thermal profile between present approach and published theoretical approach for particular initial and boundary conditions inflicted in this investigation. It has been studied that maximum temperature difference of existing approach for Fourier temperature distribution is 19.6% while in case of non-Fourier, it is 52.8%. We have validated our present analysis with experimental results and it has been observed that the temperature response based on the spatial dependent variable initial condition matches more accurately than other approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyamine pathway inhibition as a novel therapeutic approach to treating neuroblastoma

PubMed Central

Gamble, Laura D.; Hogarty, Michael D.; Liu, Xueyuan; Ziegler, David S.; Marshall, Glenn; Norris, Murray D.; Haber, Michelle

2012-01-01

Polyamines are highly regulated essential cations that are elevated in rapidly proliferating tissues, including diverse cancers. Expression analyses in neuroblastomas suggest that up-regulation of polyamine pro-synthetic enzymes and down-regulation of catabolic enzymes is associated with poor prognosis. Polyamine sufficiency may be required for MYCN oncogenicity in MYCN amplified neuroblastoma, and targeting polyamine homeostasis may therefore provide an attractive therapeutic approach. ODC1, an oncogenic MYCN target, is rate-limiting for polyamine synthesis, and is overexpressed in many cancers including neuroblastoma. Inhibition of ODC1 by difluoromethylornithine (DFMO) decreased tumor penetrance in TH-MYCN mice treated pre-emptively, and extended survival and synergized with chemotherapy in treating established tumors in both TH-MYCN and xenograft models. Efforts to augment DFMO activity, or otherwise maximally reduce polyamine levels, are focused on antagonizing polyamine uptake or augmenting polyamine export or catabolism. Since polyamine inhibition appears to be clinically well tolerated, these approaches, particularly when combined with chemotherapy, have great potential for improving neuroblastoma outcome in both MYCN amplified and non-MYCN amplified neuroblastomas. PMID:23181218

On the advancement of therapeutic penality: therapeutic authority, personality science and the therapeutic community.

PubMed

McBride, Ruari-Santiago

2017-09-01

In this article I examine the advancement of therapeutic penality in the UK, a penal philosophy that reimagines prison policy, practices and environments utilising psychological knowledge. Adopting a historical approach, I show how modern therapeutic penality is linked to the emergence of personality science in the nineteenth century and the development of the democratic therapeutic community (DTC) model in the twentieth century. I outline how at the turn of the twenty-first century a catalytic event generated a moral panic that led the British government to mobilise psychological knowledge and technologies in an attempt to manage dangerous people with severe personality disorder. Tracing subsequent developments, I argue psychological ways of talking, thinking and acting have obtained unparalleled salience in domains of penality and, in turn, radically transformed the conditions of imprisonment. © 2017 Foundation for the Sociology of Health & Illness.

How do the features of mindfulness-based cognitive therapy contribute to positive therapeutic change? A meta-synthesis of qualitative studies.

PubMed

Cairns, Victoria; Murray, Craig

2015-05-01

The exploration of Mindfulness-based Cognitive Therapy through qualitative investigation is a growing area of interest within current literature, providing valuable understanding of the process of change experienced by those engaging in this therapeutic approach. This meta-synthesis aims to gain a deeper understanding of how the features of Mindfulness-based Cognitive Therapy contribute to positive therapeutic change. Noblit and Hare's (1988) 7-step meta-ethnography method was conducted in order to synthesize the findings of seven qualitative studies. The process of reciprocal translation identified the following five major themes: i) Taking control through understanding, awareness and acceptance; ii) The impact of the group; (iii) Taking skills into everyday life; (iv) Feelings towards the self; (v) The role of expectations. The synthesis of translation identified the higher order concept of "The Mindfulness-based Cognitive Therapy Journey to Change", which depicts the complex interaction between the five themes in relation to how they contribute to positive therapeutic change. The findings are discussed in relation to previous research, theory and their implications for clinical practice.

ABO-incompatible blood transfusion and invasive therapeutic approaches during pediatric cardiopulmonary bypass.

PubMed

Aliç, Yasin; Akpek, Elif A; Dönmez, Asli; Ozkan, Süleyman; Perfusionist, Güray Yener; Aslamaci, Sait

2008-10-01

Human error has been identified as a major source of ABO-incompatible blood transfusion which most often results from blood being given to the wrong patient. We present a case of inadvertent administration of ABO-incompatible blood to a 6-mo-old child who underwent congenital heart surgery and discuss the use of invasive therapeutic approaches. Invasive techniques included total circulatory arrest and large-volume exchange transfusion, along with conventional ultrafiltration and plasmapheresis, which could all be performed rapidly and effectively. The combination of standard pharmacologic therapies and alternative invasive techniques after a massive ABO-incompatible blood transfusion led to a favorable outcome in our patient.

Antibody Therapeutics in Oncology.

PubMed

Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

2016-03-01

One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment.

[Multiple myeloma: current therapeutic approaches].

PubMed

Troussard, X; Bauduer, F; Leporrier, M

1992-01-01

The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be treated. The Melphalan Prednisone regimen is the reference for induction therapy because polychemotherapies are generally not superior. At this phase, the addition of Interferon alpha seems to be interesting. This drug has an important role during the steady-state phase. VAD represents the most efficient chemotherapy. Body hemi-irradiation is also useful. The analgesic effect and the decrease in the tumoral mass are the striking effects of this treatment. In young patients, high dose chemotherapy with bone marrow transplantation is proposed. Verapamil and anti-IL6 antibodies are currently being evaluated. Symptomatic treatment is essential in this non curable disease.

Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches.

PubMed

Zhang, Xi-Feng; Liu, Zhi-Guo; Shen, Wei; Gurunathan, Sangiliyandi

2016-09-13

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs.

Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

PubMed Central

Zhang, Xi-Feng; Liu, Zhi-Guo; Shen, Wei; Gurunathan, Sangiliyandi

2016-01-01

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. PMID:27649147

Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer

PubMed Central

Jung, Hae Rim; Park, Hee Seo; Park, Sungjin; Ahn, Young Zoo; Huh, Iksoo; Balch, Curt; Ku, Ja-Lok; Powis, Garth; Park, Taesung; Jeong, Jin-Hyun; Kim, Yon Hui

2016-01-01

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer “Big Data” has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors. To develop evidence-based precision medicine for heterogeneous cancers, we established a systematic approach to integrate transcriptomic and genomic data. Predicted signaling subpathways were then laboratory-validated both in vitro and in vivo, resulting in the identification of new candidate therapeutic targets. Here, we show: i) differences in RHOA expression patterns, and its pathway activity, between Asian and Caucasian GC tumors; ii) in vitro and in vivo perturbed RHOA expression inhibits GC cell growth in high RHOA-expressing cell lines; iii) inverse correlation between RHOA and RHOB expression; and iv) an innovative small molecule design strategy for RHOA inhibitors. In summary, RHOA, and its oncogenic signaling pathway, represent a strong biomarker-driven therapeutic target for Asian GC. This comprehensive strategy represents a promising approach for the development of “hit” compounds. PMID:27806312

Teaching clinical pharmacology and therapeutics with an emphasis on the therapeutic reasoning of undergraduate medical students

PubMed Central

Richir, Milan C.; Tichelaar, Jelle; Geijteman, Eric C. T.

2008-01-01

Background The rational prescribing of drugs is an essential skill of medical doctors. Clinical pharmacologists play an important role in the development of these skills by teaching clinical pharmacology and therapeutics (CP&T) to undergraduate medical students. Although the approaches to teaching CP&T have undergone many changes over the last decennia, it is essential that the actual teaching of CP&T continues to be a major part of the undergraduate medical curriculum. Objectives The learning objectives of CP&T teaching in terms of developing the therapeutic competencies of undergraduate medical students are described, with an emphasis on therapeutic decision-making. On the basis of current theories of cognitive psychology and medical education, context-learning is presented as an effective approach by which to achieve therapeutic competencies. An example of a CP&T curriculum is presented. PMID:18228012

Advances in Therapeutic Cancer Vaccines.

PubMed

Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

2016-01-01

Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. © 2016 Elsevier Inc. All rights reserved.

Exploration of developmental approaches to companion animal antimicrobials: providing for the unmet therapeutic needs of dogs and cats.

PubMed

Apley, M; Claxton, R; Davis, C; DeVeau, I; Donecker, J; Lucas, A; Neal, A; Papich, M

2010-04-01

The American Academy of Veterinary Pharmacology and Therapeutics (AAVPT) and the United States Pharmacopeia (USP) co-sponsored a workshop to explore approaches for developing companion animal antimicrobials. This workshop was developed in response to the shortage of antimicrobials labeled for dogs and cats, as there is a shortage of approved antimicrobials for the range of infectious diseases commonly treated in small animal practice. The objective of the workshop was to identify alternative approaches to data development to support new indications consistent with the unmet therapeutic needs of dogs and cats. The indications for currently approved antimicrobials do not reflect the broader range of infectious diseases that are commonly diagnosed and treated by the veterinarian. Therefore, the labels for these approved antimicrobials provide limited information to the veterinarian for appropriate therapeutic decision-making beyond the few indications listed. Industry, veterinary practice, and regulatory challenges to the development of new antimicrobial indications were discussed. The workshop resulted in short- and long-term recommendations. Short-term recommendations focus on the use of additional data considerations for product labeling. Long-term recommendations center on legislative or regulatory legal initiatives. The workshop recommendations will need collaboration from industry, academia, and regulatory authorities and a legal shift in the drug approval and availability processes.

Therapeutic friendliness and the development of therapeutic leverage by mental health nurses in community rehabilitation settings.

PubMed

Gardner, Andrew

2010-01-01

In a world dominated by technology and driven by fiscal policy emphasis, the therapeutic relationship as a healing modality is still a central theme to mental health nurses (MHN) in their everyday work. This research, as part of a PhD program, used a constructivist grounded theory approach to explore the process of therapeutic relationships and professional boundaries. The current paper outlines how therapeutic friendliness provides a connection for the therapeutic relationship to develop but in doing so requires a balancing of the therapeutic relationship and constant maintenance of the professional boundary. The authors also discuss how community mental health nurses (CMHN) invest in the therapeutic relationship in order to develop a therapeutic alliance and how the alliance between the CMHN and the client facilitates the use of therapeutic leverage applied by the CMHN as part of the therapeutic process.

Therapeutic approach to bronchiolitis: why pediatricians continue to overprescribe drugs?

PubMed Central

2010-01-01

Background Bronchiolitis guidelines suggest that neither bronchodilators nor corticosteroids, antiviral and antibacterial agents should be routinely used. Although recommendations, many clinicians persistently prescribe drugs for bronchiolitis. Aim of the study To unravel main reasons of pediatricians in prescribing drugs to infants with bronchiolitis, and to possibly correlate therapeutic choices to the severity of clinical presentation. Also possible influence of socially deprived condition on therapeutic choices is analyzed. Methods Patients admitted to Pediatric Division of 2 main Hospitals of Naples because of bronchiolitis in winter season 2008-2009 were prospectively analyzed. An RDAI (Respiratory Distress Assessment Instrument) score was assessed at different times from admission. Enrolment criteria were: age 1-12 months; 1st lower respiratory infection with cough and rhinitis with/without fever, wheezing, crackles, tachypnea, use of accessory muscles, and/or nasal flaring, low oxygen saturation, cyanosis. Social deprivation status was assessed by evaluating school graduation level of the origin area of the patients. A specific questionnaire was submitted to clinicians to unravel reasons of their therapeutic behavior. Results Eighty-four children were enrolled in the study. Mean age was 3.5 months. Forty-four per cent of patients presented with increased respiratory rate, 70.2% with chest retractions, and 7.1% with low SaO2. Mean starting RDAI score was 8. Lung consolidation was found in 3.5% on chest roentgenogram. Data analysis also unraveled that 64.2% matched clinical admission criteria. Social deprivation status analysis revealed that 72.6% of patients were from areas "at social risk". Evaluation of length of stay vs. social deprivation status evidenced no difference between "at social risk" and "not at social risk" patients. Following therapeutic interventions were prescribed: nasal suction (64.2%), oxygen administration (7.1%), antibiotics (50

Fetal hemoglobin regulation in β-thalassemia: heterogeneity, modifiers and therapeutic approaches.

PubMed

Sripichai, Orapan; Fucharoen, Suthat

2016-12-01

Stress erythropoiesis induces fetal hemoglobin (HbF) expression in β-thalassemias, however the level of expression is highly variable. The last decade has seen dramatic advances in our understanding of the molecular regulators of HbF production and the genetic factors associated with HbF levels, leading to the promise of new methods of the clinical induction of HbF. Areas covered: This article will review the heterogeneity and genetic modifiers of HbF and HbF induction therapy in β-thalassemia. Expert commentary: One promising curative β-thalassemia therapy is to induce HbF synthesis in β-thalassemic erythrocytes to therapeutic levels before clinical symptom occurs. Further understanding of HbF level variation and regulation is needed in order to predict the response from HbF-inducing approaches.

Pediatric minor head trauma: do cranial CT scans change the therapeutic approach?

PubMed

Andrade, Felipe P; Montoro, Roberto; Oliveira, Renan; Loures, Gabriela; Flessak, Luana; Gross, Roberta; Donnabella, Camille; Puchnick, Andrea; Suzuki, Lisa; Regacini, Rodrigo

2016-10-01

1) To verify clinical signs correlated with appropriate cranial computed tomography scan indications and changes in the therapeutic approach in pediatric minor head trauma scenarios. 2) To estimate the radiation exposure of computed tomography scans with low dose protocols in the context of trauma and the additional associated risk. Investigators reviewed the medical records of all children with minor head trauma, which was defined as a Glasgow coma scale ≥13 at the time of admission to the emergency room, who underwent computed tomography scans during the years of 2013 and 2014. A change in the therapeutic approach was defined as a neurosurgical intervention performed within 30 days, hospitalization, >12 hours of observation, or neuro-specialist evaluation. Of the 1006 children evaluated, 101 showed some abnormality on head computed tomography scans, including 49 who were hospitalized, 16 who remained under observation and 36 who were dismissed. No patient underwent neurosurgery. No statistically significant relationship was observed between patient age, time between trauma and admission, or signs/symptoms related to trauma and abnormal imaging results. A statistically significant relationship between abnormal image results and a fall higher than 1.0 meter was observed (p=0.044). The mean effective dose was 2.0 mSv (0.1 to 6.8 mSv), corresponding to an estimated additional cancer risk of 0.05%. A computed tomography scan after minor head injury in pediatric patients did not show clinically relevant abnormalities that could lead to neurosurgical indications. Patients who fell more than 1.0 m were more likely to have changes in imaging tests, although these changes did not require neurosurgical intervention; therefore, the use of computed tomography scans may be questioned in this group. The results support the trend of more careful indications for cranial computed tomography scans for children with minor head trauma.

Addressing hopelessness in people with suicidal ideation: building upon the therapeutic relationship utilizing a cognitive behavioural approach.

PubMed

Collins, S; Cutcliffe, J R

2003-04-01

This article reports on how the therapeutic relationship can be enhanced by utilizing a cognitive behavioural approach when dealing with hopelessness in suicidal people. A rationale is presented regarding why this topic is deemed important. Following a brief overview of the concept of hope, the theoretical and empirical literature relating to hopelessness are examined. This literature indicates that, given the inextricable link between suicide and a sense of pervasive hopelessness, it is necessary for the practitioner to understand the methods and theoretical underpinnings of hope inspiration. Two case studies, drawn from clinical practice, are described in order to elucidate the key elements/interventions (which include the therapeutic relationship and specific cognitive behavioural techniques that the nurse therapist may utilize when attempting to ameliorate the client's sense of hopelessness). These key elements/interventions are further elaborated upon. Whilst cognitive behavioural techniques are shown to be beneficial when dealing with hopelessness, it is advocated that the therapeutic relationship is a prerequisite for successful therapy.

Blood–brain barrier dysfunction and epilepsy: Pathophysiologic role and therapeutic approaches

PubMed Central

Marchi, Nicola; Granata, Tiziana; Ghosh, Chaitali; Janigro, Damir

2016-01-01

The blood–brain barrier (BBB) is located within a unique anatomic interface and has functional ramifications to most of the brain and blood cells. In the past, the BBB was considered a pharmacokinetic impediment to antiepileptic drug penetration into the brain; nowadays it is becoming increasingly evident that targeting of the damaged or dysfunctional BBB may represent a therapeutic approach to reduce seizure burden. Several studies have investigated the mechanisms linking the onset and sustainment of seizures to BBB dysfunction. These studies have shown that the BBB is at the crossroad of a multifactorial pathophysiologic process that involves changes in brain milieu, altered neuroglial physiology, development of brain inflammation, leukocyte–endothelial interactions, faulty angiogenesis, and hemodynamic changes leading to energy mismatch. A number of knowledge gaps, conflicting points of view, and discordance between clinical and experimental data currently characterize this field of neuroscience. As more pieces are added to this puzzle, it is apparent that each mechanism needs to be validated in an appropriate clinical context. We now offer a BBB-centric view of seizure disorders, linking several aspects of seizures and epilepsy physiopathology to BBB dysfunction. We have reviewed the therapeutic, antiseizure effect of drugs that promote BBB repair. We also present BBB neuroimaging as a tool to correlate BBB restoration to seizure mitigation. Add-on cerebrovascular drug could be of efficacy in reducing seizure burden when used in association with neuronal antiepileptic drugs. PMID:22905812

Towards new therapeutic approaches for malignant melanoma.

PubMed

Pacheco, Ivan; Buzea, Cristina; Tron, Victor

2011-11-01

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

Therapeutic jurisprudence and sex offenders: a psycho-legal approach to protection.

PubMed

Birgden, Astrid

2004-10-01

Societal response to sex offenders is marked by uncertainty about whether punishment or treatment should occur. The distinction between punishment, prevention, and protection is useful to determine how best to assess, treat, and manage sex offenders within the criminal justice system. Once convicted, both law and psychology are concerned with sex offenders changing their behavior in order to protect the community. Therapeutic jurisprudence is a legal theory that aims to maximize therapeutic effects of the law and minimize anti-therapeutic consequences of the law. Therapeutic jurisprudence provides a framework to combine legal and psychological processes to balance prevention and protection. Legal and correctional practitioners can work together to address both community protection and offender protection concerns.

Therapeutic approaches for HER2-positive brain metastases: Circumventing the blood–brain barrier

PubMed Central

Mehta, Ankit I.; Brufsky, Adam M.; Sampson, John H.

2015-01-01

We aim to summarize data from studies of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and brain metastasis and to describe novel methods being developed to circumvent the blood–brain barrier (BBB). A literature search was conducted to obtain data on the clinical efficacy of trastuzumab and lapatinib in patients with HER2-positive MBC and brain metastasis, as well as the transport of therapeutic molecules across the BBB. Trastuzumab-based therapy is the standard of care for patients with HER2-positive MBC. Post hoc and retrospective analyses show that trastuzumab significantly prolongs overall survival when given after the diagnosis of central nervous system (CNS) metastasis; this is probably attributable to its control of extracranial disease, although trastuzumab may have a direct effect on CNS disease in patients with local or general perturbation of the BBB. In patients without a compromised BBB, trastuzumab is thought to have limited access to the brain, because of its relatively large molecular size. Several approaches are being developed to enhance the delivery of therapeutic agents to the brain. These include physical or pharmacologic disruption of the BBB, direct intracerebral drug delivery, drug manipulation, and coupling drugs to transport vectors. Available data suggest that trastuzumab extends survival in patients with HER2-positive MBC and brain metastasis. Novel methods for delivery of therapeutic agents into the brain could be used in the future to enhance access to the CNS by trastuzumab, thereby improving its efficacy in this setting. PMID:22727691

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

PubMed

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

A prodrug approach to the use of coumarins as potential therapeutics for superficial mycoses.

PubMed

Mercer, Derry K; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S; O Neil, Deborah A

2013-01-01

Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20-25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones.

A Prodrug Approach to the Use of Coumarins as Potential Therapeutics for Superficial Mycoses

PubMed Central

Mercer, Derry K.; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S.; O′Neil, Deborah A.

2013-01-01

Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20–25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones. PMID:24260474

Psychosocial factors and therapeutic approaches in the context of sexual history taking in men: a study conducted among Swiss general practitioners and urologists.

PubMed

Platano, Giacomo; Margraf, Jürgen; Alder, Judith; Bitzer, Johannes

2008-11-01

Male sexual dysfunction is a common medical condition, which is addressed mainly from a biomedical perspective by Swiss general practitioners (GPs) and urologists as the results of part I of our study showed. A psychosocial orientation in sexual history taking (SHT) leads to a truly patient-centered approach and is crucial for improving therapy decisions related to sexual dysfunction. To analyze to what extent Swiss GPs and urologists have a psychosocial orientation in SHT, and what therapeutic options they focus on when confronted with male sexual dysfunction. A semistructured interview was developed and used in face-to-face encounters with 25 GPs and 25 urologists. Content and frequency of interview responses. The GPs and urologists differed significantly from each other in 5 out of 22 psychosocial factors. Summarizing these psychosocial factors in four domains showed a difference between the GPs and urologists in only one domain. Both groups focus on an open conversation as their approach in SHT. No GP and only a minority of urologists based their diagnosis on criteria of the International Classification of Diseases (10th edition) (ICD-10) or Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). The GPs and urologists differed significantly from each other in 4 out of 16 combinations resulting from the given therapeutic options and form of sexual dysfunction. The urologists focus more strongly on medication as a therapeutic option. The results of part II additionally justify establishing guidelines and training resources related to SHT in Switzerland. Swiss physicians should be encouraged to apply a more psychosocial orientation in SHT. This will contribute to a better patient-centered approach with positive consequences on physicians' therapeutic decisions. Optimizing the approach in SHT and the choice of therapeutic options may better facilitate real sexual satisfaction for the patient and ultimately result in fewer health insurance

Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.

PubMed

Schaeffer, Evelin L; Forlenza, Orestes V; Gattaz, Wagner F

2009-01-01

Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.

Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part I: Curcumin.

PubMed

Di Martino, Rita Maria Concetta; Luppi, Barbara; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Abruzzo, Angela; Belluti, Federica

2017-05-01

curcumin is the main bioactive component contained in Curcuma Longa, largely employed in traditional medicine. Recently, beneficial properties, useful for prevention and treatment of several disorders, have been discovered for this compound. Peculiar structural feature is an α,β-unsaturated carbonyl system essential for establishing contacts with critical cysteine residues of several targets. This distinctive mechanism of action imparts to the molecule the ability to affect a large number of targets, accounting for its pleiotropic behaviour and definition of "privileged structure". Areas covered: The objective of the review is an examination of the recent developments in the field of the anti-cancer applications of curcumin, together with formulation issues, considering the patent literature in the years 2012-2016. Expert opinion: The wide therapeutic efficacy of curcumin is related to synergistic interactions with several biological targets, along with the modulation of several signaling pathways. This peculiar behaviour could be useful in the treatment of multifactorial diseases such as cancer. Combination of curcumin with a first line antineoplastic drug proved to be a valuable strategy to obtain an amplified response with minimized side effects. Innovative curcumin formulations based on the nanotechnology approach allowed improving both bioavailability and therapeutic efficacy.

[Psychopathology and film: a valuable interaction?].

PubMed

van Duppen, Z; Summa, M; Fuchs, T

2015-01-01

Film or film fragments are often used in psychopathology education. However, so far there have been very few articles that have discussed the benefits and limitations of using films to explain or illustrate psychopathology. Although numerous films involves psychopathology in varying degrees, it is not clear how we can use films for psychopathology education. To examine the advantages, limitations and possible methods of using film as a means of increasing our knowledge and understanding of psychiatric illnesses. We discuss five examples that illustrate the interaction of film and psychopathology. On the one hand we explain how the psychopathological concepts are used in each film and on the other hand we explain which aspects of each film are valuable aids for teaching psychopathology. The use of film makes it possible to introduce the following topics in psychopathological teaching programme: holistic psychiatric reasoning, phenomenology and the subjective experience, the recognition of psychopathological prototypes and the importance of context. There is undoubtedly an analogy between the method we have chosen for teaching psychopathology with the help of films and the holistic approach of the psychiatrist and his or her team. We believe psychopathology education can benefit from films and we would recommend our colleagues to use it in this way.

Therapeutic Inertia and Treatment Intensification.

PubMed

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Cardiotoxicity of the new cancer therapeutics- mechanisms of, and approaches to, the problem

PubMed Central

Force, Thomas; Kerkelä, Risto

2009-01-01

Cardiotoxicity of some targeted therapeutics, including monoclonal antibodies and small molecule inhibitors, is a reality. Herein we will examine why it occurs, focusing on molecular mechanisms to better understand the issue. We will also examine how big the problem is and, more importantly, how big it may become in the future. We will review models for detecting cardiotoxicity in the pre-clinical phase. We will also focus on two key areas that drive cardiotoxicity- multi-targeting and the inherent lack of selectivity of ATP-competitive antagonists. Finally, we will examine the issue of reversibility and discuss possible approaches to keeping patients on therapy. PMID:18617014

Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

NASA Astrophysics Data System (ADS)

Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

2016-11-01

In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially misfolded intermediates aggregate via the interaction with the complementary intermediates and consequently enhance oligomers formation that grows into fibrils and proto-fibrils. The amyloid fibrils for example, accumulate in the brain and central nervous system (CNS) as amyloid deposits in the Parkinson's disease (PD), Alzheimer's disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other neurodegenerative diseases. Treatment of such misfolding maladies is considered as one of the most important challenges of the 21st century. Currently, several treatments strategies have been and are being discovered. These therapeutic interventions partly reversed or prevented the pathological state. More recently, a new approach was discovered, which employs nanobodies that targets multisteps in fibril formation pathway that may possibly completely cure these misfolding diseases. Keeping the above views in mind in the current review, we have comprehensively discussed the different mechanisms underlying protein misfolding thereby leading to diseases conditions and their therapeutic interventions.

Ravens reconcile after aggressive conflicts with valuable partners.

PubMed

Fraser, Orlaith N; Bugnyar, Thomas

2011-03-25

Reconciliation, a post-conflict affiliative interaction between former opponents, is an important mechanism for reducing the costs of aggressive conflict in primates and some other mammals as it may repair the opponents' relationship and reduce post-conflict distress. Opponents who share a valuable relationship are expected to be more likely to reconcile as for such partners the benefits of relationship repair should outweigh the risk of renewed aggression. In birds, however, post-conflict behavior has thus far been marked by an apparent absence of reconciliation, suggested to result either from differing avian and mammalian strategies or because birds may not share valuable relationships with partners with whom they engage in aggressive conflict. Here, we demonstrate the occurrence of reconciliation in a group of captive subadult ravens (Corvus corax) and show that it is more likely to occur after conflicts between partners who share a valuable relationship. Furthermore, former opponents were less likely to engage in renewed aggression following reconciliation, suggesting that reconciliation repairs damage caused to their relationship by the preceding conflict. Our findings suggest not only that primate-like valuable relationships exist outside the pair bond in birds, but that such partners may employ the same mechanisms in birds as in primates to ensure that the benefits afforded by their relationships are maintained even when conflicts of interest escalate into aggression. These results provide further support for a convergent evolution of social strategies in avian and mammalian species.

Extraction of valuable compounds from mangosteen pericarps by hydrothermal assisted sonication

NASA Astrophysics Data System (ADS)

Machmudah, Siti; Lestari, Sarah Duta; Shiddiqi, Qifni Yasa'Ash; Widiyastuti, Winardi, Sugeng; Wahyudiono, Kanda, Hideki; Goto, Motonobu

2015-12-01

Valuable compounds, such as xanthone and phenolic compounds, from mangosteen pericarps was extracted by hydrothermal treatment at temperatures of 120-160 °C and pressures of 5 MPa using batch and semi-batch extractor. This method is a simple and environmentally friendly extraction method requiring no chemicals other than water. Under these conditions, there is possibility for the formation of phenolic compounds from mangosteen pericarps from decomposition of bounds between lignin, cellulose, and hemicellulose via autohydrolysis. In order to increase the amount of extracted valuable compounds, sonication pre-treament was performed prior to the hydrothermal extraction process. 30 min of sonication pre-treatment could increase significantly the amount of xanthone and phenolic compounds mangosteen pericarps extraction. In batch-system, the xanthone recovery approach to 100 % at 160 °C with 30 min sonication pre-treatment for 150 min extraction time. Under semi-batch process, the total phenolic compounds in the extract was 217 mg/g sample at 160 °C with 30 min sonication pre-treatment for 150 min total extraction time. The results revealed that hydrothermal extraction assisted sonication pre-treatment is applicable method for the isolation of polyphenolic compounds from other types of biomass and may lead to an advanced plant biomass components extraction technology.

Therapeutic use of nicergoline.

PubMed

Winblad, Bengt; Fioravanti, Mario; Dolezal, Tomas; Logina, Inara; Milanov, Ivan Gospodinov; Popescu, Dinu Cristian; Solomon, Alina

2008-01-01

The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

PubMed

Rahman, Wahida; Dickenson, Anthony H

2015-06-01

Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics. Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy. Somatosensory phenotyping of chronic pain patients, as a surrogate of putative pain generating mechanisms, may predict patient response to treatment. Identification of new targets will inform and guide future research, aiding the development of more effective analgesics. Future clinical trial designs should implement sensory phenotyping of patients, as an inclusion or stratification criterion, in order to establish an individualized, mechanism-based treatment of osteoarthritis pain.

Translating Discovery in Zebrafish Pancreatic Development to Human Pancreatic Cancer: Biomarkers, Targets, Pathogenesis, and Therapeutics

PubMed Central

Kazi, Abid A.; Yee, Rosemary K.

2013-01-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer. PMID:23682805

Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

PubMed

Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

2013-06-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

Development of Nanoscale Approaches for Ovarian Cancer Therapeutics and Diagnostics

PubMed Central

Engelberth, Sarah A.; Hempel, Nadine; Bergkvist, Magnus

2014-01-01

Ovarian cancer is the deadliest of all gynecological cancers and the fifth leading cause of death due to cancer in women. This is largely due to late-stage diagnosis, poor prognosis related to advanced-stage disease, and the high recurrence rate associated with development of chemoresistance. Survival statistics have not improved significantly over the last three decades, highlighting the fact that improved therapeutic strategies and early detection require substantial improvements. Here, we review and highlight nanotechnology-based approaches that seek to address this need. The success of Doxil, a PEGylated liposomal nanoencapsulation of doxorubicin, which was approved by the FDA for use on recurrent ovarian cancer, has paved the way for the current wave of nanoparticle formulations in drug discovery and clinical trials. We discuss and summarize new nanoformulations that are currently moving into clinical trials and highlight novel nanotherapeutic strategies that have shown promising results in preclinical in vivo studies. Further, the potential for nanomaterials in diagnostic imaging techniques and the ability to leverage nanotechnology for early detection of ovarian cancer are also discussed. PMID:25271436

[Research on Depression in the GDR - Historical Lines of Development and Therapeutic Approaches].

PubMed

Thormann, J; Himmerich, H; Steinberg, H

2014-02-01

Historical research has raised the issue of whether GDR psychiatry was isolated from Western influences to such an extent that an autonomous East German psychiatry developed. Taking a chronological approach and being based on a clearly defined range of topics, the objective of this paper is to identify specific contributions made by GDR psychiatry to academic research as well as the degree of its international orientation by focusing on the treatment and research on depression. We have performed a systematic review of the East German psychiatric journal "Psychiatrie, Neurologie und medizinische Psychologie" and a screening of all psychiatric textbooks that appeared in the GDR. Although East German psychiatry was oriented towards Soviet as well as Western developments, some internationally used therapeutic or conceptual innovations reached East German clinics only with some delay. Yet, East German psychiatrists have also contributed their own, independent nosological and therapeutic concepts to research on depression. Pivotal figures included, among others, R. Lemke (Jena), D. Müller-Hegemann (Leipzig) or K. Leonhard (Berlin). With regard to research on depression one cannot truly speak of an autonomous East German psychiatry. Developments in East and West were largely running in parallel. © Georg Thieme Verlag KG Stuttgart · New York.

A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.

PubMed

Amini, Elham; Rezaei, Mohsen; Mohamed Ibrahim, Norlinah; Golpich, Mojtaba; Ghasemi, Rasoul; Mohamed, Zahurin; Raymond, Azman Ali; Dargahi, Leila; Ahmadiani, Abolhassan

2015-08-01

Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great

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

PubMed Central

2012-01-01

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. PMID:23351279

Therapeutics for Equine Endocrine Disorders.

PubMed

Durham, Andy E

2017-04-01

Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

The Roman-Irish Bath: Medical/health history as therapeutic assemblage.

PubMed

Foley, Ronan

2014-04-01

The invention of a new form of hot-air bath in Blarney, Ireland in 1856, variously known in its lifetime as the Roman-Irish or Turkish Bath, acted as the starting point for a the production of a globalised therapeutic landscape. Tracking the diffusion of the Roman-Irish bath template from its local invention in Ireland to a global reach across the Victorian world and recognizing its place within a wider hydrotherapeutic history, this paper frames that diffusion as a valuable empirical addition to assemblage theory. The specific empirical history of the spread of the Roman-Irish/Turkish bath idea is drawn from primary archival and secondary historical sources. It is then discussed and, drawing from work on assemblage theory, analyzed against three broad themes: mobile networks, socio-material practices and contested emergence. The emergent relational geographies of the Roman-Irish Bath identify important roles for the diffusion and transformation of specific medical settings, identities and functions. These were linked in turn to competing social-healing pathways wherein bodies were technologically and morally managed, to produce a more inhabited form of therapeutic assemblage. In all cases the differential diffusion of the bath idea, it's shifting and fractured material forms and multiple inhabitations and discourses were contested and mobile and spoke to an assemblage approach which has ripe potential for exploration across a range of medical/health geography settings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Systems Bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches.

PubMed

Oulas, Anastasis; Minadakis, George; Zachariou, Margarita; Sokratous, Kleitos; Bourdakou, Marilena M; Spyrou, George M

2017-11-27

Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics. Systems Bioinformatics is the framework in which systems approaches are applied to such data, setting the level of resolution as well as the boundary of the system of interest and studying the emerging properties of the system as a whole rather than the sum of the properties derived from the system's individual components. A key approach in Systems Bioinformatics is the construction of multiple networks representing each level of the omics spectrum and their integration in a layered network that exchanges information within and between layers. Here, we provide evidence on how Systems Bioinformatics enhances computational therapeutics and diagnostics, hence paving the way to precision medicine. The aim of this review is to familiarize the reader with the emerging field of Systems Bioinformatics and to provide a comprehensive overview of its current state-of-the-art methods and technologies. Moreover, we provide examples of success stories and case studies that utilize such methods and tools to significantly advance research in the fields of systems biology and systems medicine. © The Author 2017. Published by Oxford University Press.

Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

PubMed

Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

2016-01-01

This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

PubMed Central

Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

2016-01-01

This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

Valuable Nutrients and Functional Bioactives in Different Parts of Olive (Olea europaea L.)—A Review

PubMed Central

Ghanbari, Rahele; Anwar, Farooq; Alkharfy, Khalid M.; Gilani, Anwarul-Hassan; Saari, Nazamid

2012-01-01

The Olive tree (Olea europaea L.), a native of the Mediterranean basin and parts of Asia, is now widely cultivated in many other parts of the world for production of olive oil and table olives. Olive is a rich source of valuable nutrients and bioactives of medicinal and therapeutic interest. Olive fruit contains appreciable concentration, 1–3% of fresh pulp weight, of hydrophilic (phenolic acids, phenolic alchohols, flavonoids and secoiridoids) and lipophilic (cresols) phenolic compounds that are known to possess multiple biological activities such as antioxidant, anticarcinogenic, antiinflammatory, antimicrobial, antihypertensive, antidyslipidemic, cardiotonic, laxative, and antiplatelet. Other important compounds present in olive fruit are pectin, organic acids, and pigments. Virgin olive oil (VOO), extracted mechanically from the fruit, is also very popular for its nutritive and health-promoting potential, especially against cardiovascular disorders due to the presence of high levels of monounsaturates and other valuable minor components such as phenolics, phytosterols, tocopherols, carotenoids, chlorophyll and squalene. The cultivar, area of production, harvest time, and the processing techniques employed are some of the factors shown to influence the composition of olive fruit and olive oil. This review focuses comprehensively on the nutrients and high-value bioactives profile as well as medicinal and functional aspects of different parts of olives and its byproducts. Various factors affecting the composition of this food commodity of medicinal value are also discussed. PMID:22489153

Tick-borne viruses: a review from the perspective of therapeutic approaches.

PubMed

Lani, Rafidah; Moghaddam, Ehsan; Haghani, Amin; Chang, Li-Yen; AbuBakar, Sazaly; Zandi, Keivan

2014-09-01

Several important human diseases worldwide are caused by tick-borne viruses. These diseases have become important public health concerns in recent years. The tick-borne viruses that cause diseases in humans mainly belong to 3 families: Bunyaviridae, Flaviviridae, and Reoviridae. In this review, we focus on therapeutic approaches for several of the more important tick-borne viruses from these 3 families. These viruses are Crimean-Congo hemorrhagic fever virus (CCHF) and the newly discovered tick-borne phleboviruses, known as thrombocytopenia syndromevirus (SFTSV), Heartland virus and Bhanja virus from the family Bunyaviridae, tick-borne encephalitis virus (TBEV), Powassan virus (POWV), Louping-ill virus (LIV), Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV), and Alkhurma hemorrhagic fever virus (AHFV) from the Flaviviridae family. To date, there is no effective antiviral drug available against most of these tick-borne viruses. Although there is common usage of antiviral drugs such as ribavirin for CCHF treatment in some countries, there are concerns that ribavirin may not be as effective as once thought against CCHF. Herein, we discuss also the availability of vaccines for the control of these viral infections. The lack of treatment and prevention approaches for these viruses is highlighted, and we hope that this review may increase public health awareness with regard to the threat posed by this group of viruses. Copyright © 2014 Elsevier GmbH. All rights reserved.

Therapeutic Approaches of Botulinum Toxin in Gynecology.

PubMed

Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

2018-04-21

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

Therapeutic landscapes and postcolonial theory: a theoretical approach to medical tourism.

PubMed

Buzinde, Christine N; Yarnal, Careen

2012-03-01

This paper draws on two conceptual frameworks, therapeutic landscapes and postcolonial theory, to discuss aspects of medical tourism not addressed in extant literature. Building on the intersection between postcolonial and therapeutic landscapes scholarship, it highlights inequalities related to the production of national therapeutic landscapes located in postcolonial regions as well as their discursive (re)positioning as medical tourism destinations. As a framework, therapeutic landscapes can facilitate an understanding of medical tourism sites as curative spaces which combine modern and alternative forms of medicine with travel and leisure. Postcolonial theory critiques the economic, moral and cultural tensions emerging from the intersection between corporations that provide cheaper and more attractive medical services, and the nations on the periphery struggling to offer high medical standards that may not be accessible to their own local populations. In an effort to enhance scholarship on medical tourism, these conceptual frameworks are offered as points of departure, rather than sites of arrival, through which critical dialog on medical tourism can be sustained and broadened. Copyright © 2012 Elsevier Ltd. All rights reserved.

ADVANCED MOLECULAR DESIGN OF BIOPOLYMERS FOR TRANSMUCOSAL AND INTRACELLULAR DELIVERY OF CHEMOTHERAPEUTIC AGENTS AND BIOLOGICAL THERAPEUTICS

PubMed Central

Liechty, William B.; Caldorera-Moore, Mary; Phillips, Margaret A.; Schoener, Cody; Peppas, Nicholas A.

2011-01-01

Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious materials selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids. PMID:21699934

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.

PubMed

Ahmad, Zulfiqar; Hassan, Sherif S; Azim, Sofiya

2017-11-20

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals is based on tradition or word of mouth with few evidence-based studies. Moreover, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become pertinent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can result in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase

PubMed Central

Ahmad, Zulfiqar; Hassan, Sherif S.; Azim, Sofiya

2017-01-01

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phy-tochemicals is based on tradition or word of mouth with few evidence-based studies. Moreo-ver, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become perti-nent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of die-tary phytochemicals are known to inhibit ATP synthase. Structural modifications of phyto-chemicals have been shown to increase the inhibitory potency and extent of inhibition. Site-directed mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can re-sult in selective binding and inhibition of microbial ATP synthase. In this review, the therapeu-tic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective target-ing of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. PMID:28831918

[The necessity of new approaches to the elaboration of the projects for the sanitary (mountainous sanitary) protection districts around the therapeutic and health-promotion facilities, health resorts and their natural medical resources].

PubMed

Razumov, A N; Adilov, V B

2015-01-01

The international experience gained during the past two centuries indicates that the most efficient and rational way to ensure the protection of the territories occupied by the therapeutic and health-promotion facilities, spa centres, and health resorts together with their natural medical resources is to set up sanitary (mountainous sanitary) protection districts or zones along the perimeter of these territories. Beginning from 2000, numerous changes and amendments have been annually introduced in the Russian legislation intended to ensure efficacious control over the rational exploitation of the territories of therapeutic and health-promotion value and their natural medical resources. These initiatives have negative effect on the activities of these organizations and the quality of the services they are expected to provide. Taken together these effects lead to the degradation of the spa and health resort business. Bearing in mind the current conditions for economic activities, it is proposed, in contrast to the former global approach, to envisage in the aforementioned projects the establishment of the sanitary (mountainous sanitary) protection districts or zones and determine their borders based on the results of the assessment of their potential for the protection of therapeutic factors and other valuable resources. Equally important is the maximum reduction of the areas of the second and third zones taking into account their relevant objective characteristics. In certain cases, the protective district may coincide with the second zone. As far as the federal health resorts and large territories of special health-promotion value are concerned, some of them may have two or more sanitary (mountainous sanitary) protection districts. Both the owners and the users of these territories should be provided the necessary and sufficient possibilities for the rational nature use at the grounds and in the adjacent water areas suitable for the development of health resort

Emerging therapeutics in sleep.

PubMed

Saper, Clifford B; Scammell, Thomas E

2013-09-01

The development of new therapeutics for sleep disorders is increasingly dependent upon understanding the basic brain circuitry that underlies sleep-wake regulation, and how it may be pharmacologically manipulated. In this review, we consider the pathophysiological basis of major sleep disorders that often are seen by neurologists, including excessive daytime sleepiness, insomnia, narcolepsy, rapid eye movement sleep behavior disorder, and restless legs syndrome, as well as circadian disorders, and we review the current and potential future therapeutic approaches. Copyright © 2013 American Neurological Association.

Developing Therapeutic Listening

ERIC Educational Resources Information Center

Lee, Billy; Prior, Seamus

2013-01-01

We present an experience-near account of the development of therapeutic listening in first year counselling students. A phenomenological approach was employed to articulate the trainees' lived experiences of their learning. Six students who had just completed a one-year postgraduate certificate in counselling skills were interviewed and the…

Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

PubMed

Chen, Z; Lönnberg, T; Lahesmaa, R

2013-08-01

Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions. © 2013 John Wiley & Sons Ltd.

Therapeutic approach to chickenpox in children and adults--our experience.

PubMed

Baljic, Rusmir; Mehanic, Snjezana; Imsirovic, Bilal; Ahmetspahic-Begic, Aida; Lukovac, Enra; Baljic, Izet; Hasimbegovic-Ibrahimovic, Selma; Gazibera, Belma; Gutosic, Maho

2012-01-01

Chickenpox is highly contagious childhood disease which occurs as a result of varicella-zoster virus primary infection. Symptomatic therapy is usually adequate for chickenpox, but in some cases it requires combinations of antiviral drugs and antibiotics. To present our expirience with chickenpox therapy in children and adult patients. Study included 120 randomly chosen patients, 60 adults and 60 children, with confirmed chickenpox infection, hospitalised at Clinic for infectious diseases in Sarajevo. Observed period was 1st January 2005. to 30th June 2011. We compared used therapy and outcome of disease. We had 333 patients with confirmed chickenpox in mentioned period. Male sex prevailed. Antiviral (acyclovir) therapy was initiated in 8(13.5%) adults and 16(27%) children. Most frequently used antibiotic was Co-Amoxiclav in a group of adults and Ceftriaxone in a group of children. We use different terapeutical approaches to chickenpox according to the severity of the clinical picture and the existence of underlying diseases. Symptomatic treatment is indicated in all immunocompetent patients with no signs of complications. Use of corticosteroids remains open dillemma. Our therapeutical approcach followed by actual guidelines proved to be usefull. No death cases were recorded in these

Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

PubMed

Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

2014-01-01

It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

Therapeutic Approaches of Botulinum Toxin in Gynecology

PubMed Central

Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

2018-01-01

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration. PMID:29690530

Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery

PubMed Central

Imbrici, Paola; Liantonio, Antonella; Camerino, Giulia M.; De Bellis, Michela; Camerino, Claudia; Mele, Antonietta; Giustino, Arcangela; Pierno, Sabata; De Luca, Annamaria; Tricarico, Domenico; Desaphy, Jean-Francois; Conte, Diana

2016-01-01

In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets. PMID:27242528

Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery.

PubMed

Imbrici, Paola; Liantonio, Antonella; Camerino, Giulia M; De Bellis, Michela; Camerino, Claudia; Mele, Antonietta; Giustino, Arcangela; Pierno, Sabata; De Luca, Annamaria; Tricarico, Domenico; Desaphy, Jean-Francois; Conte, Diana

2016-01-01

In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets.

Ab Interno Trabeculectomy With the Trabectome as a Valuable Therapeutic Option for Failed Filtering Blebs.

PubMed

Wecker, Thomas; Neuburger, Matthias; Bryniok, Laura; Bruder, Kathrin; Luebke, Jan; Anton, Alexandra; Jordan, Jens F

2016-09-01

. The number of necessary IOP lowering medication drops at first, but seems to reach preoperative values after 20 months of follow-up. Trabectome surgery should be considered as a valuable escape procedure for patients with failed filtering blebs and uncontrolled IOP.

From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins.

PubMed

Verdes, Aida; Anand, Prachi; Gorson, Juliette; Jannetti, Stephen; Kelly, Patrick; Leffler, Abba; Simpson, Danny; Ramrattan, Girish; Holford, Mandë

2016-04-19

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

Bacteriophage Procurement for Therapeutic Purposes

PubMed Central

Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

2016-01-01

Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

DELIVERY OF THERAPEUTIC PROTEINS

PubMed Central

Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

2009-01-01

The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

Experimental Study of Ultrasound Contrast Agent Mediated Heat Transfer for Therapeutic Applications

NASA Astrophysics Data System (ADS)

Razansky, D.; Adam, D. R.; Einziger, P. D.

2006-05-01

Ultrasound Contrast Agents (UCA) have been recently suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by UCA, considered as disadvantageous in diagnostic imaging, might be valuable in therapeutic applications such as targeted hyperthermia or ablation treatments. The current study, based on theoretical predictions, was designed to experimentally measure the dissipation and heating effects of encapsulated UCA (Optison™) in a well-controlled and calibrated environment.

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

PubMed

Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

Characterization of Therapeutic Coatings on Medical Devices

NASA Astrophysics Data System (ADS)

Wormuth, Klaus

Therapeutic coatings on medical devices such as catheters, guide wires, and stents improve biocompatibility by favorably altering the chemical nature of the device/tissue or device/blood interface. Such coatings often minimize tissue damage (reduce friction), decrease chances for blood clot formation (prevent platelet adsorption), and improve the healing response (deliver drugs). Confocal Raman microscopy provides valuable information about biomedical coatings by, for example, facilitating the measurement of the thickness and swelling of frictionreducing hydrogel coatings on catheters and by determining the distribution of drug within a polymer-based drug-eluting coatings on stents. This chapter explores the application of Raman microscopy to the imaging of thin coatings of cross-linked poly(vinyl pyrrolidone) gels, parylene films, mixtures of dexamethasone with various polymethacrylates, and mixtures of rapamycin with hydrolysable (biodegradable) poly(lactide-co-glycolide) polymers. Raman microscopy measures the thickness and swelling of coatings, reveals the degree of mixing of drug and polymer, senses the hydrolysis of biodegradable polymers, and determines the polymorphic forms of drug present within thin therapeutic coatings on medical devices.

Valuable human capital: the aging health care worker.

PubMed

Collins, Sandra K; Collins, Kevin S

2006-01-01

With the workforce growing older and the supply of younger workers diminishing, it is critical for health care managers to understand the factors necessary to capitalize on their vintage employees. Retaining this segment of the workforce has a multitude of benefits including the preservation of valuable intellectual capital, which is necessary to ensure that health care organizations maintain their competitive advantage in the consumer-driven market. Retaining the aging employee is possible if health care managers learn the motivators and training differences associated with this category of the workforce. These employees should be considered a valuable resource of human capital because without their extensive expertise, intense loyalty and work ethic, and superior customer service skills, health care organizations could suffer severe economic repercussions in the near future.

Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches.

PubMed

Bonnet, Crystel; El-Amraoui, Aziz

2012-02-01

Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies. Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing. Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.

Therapeutic music for patients with psychiatric disorders.

PubMed

Covington, H

2001-01-01

Many patients with psychiatric disorders struggle with poor skills in coping, communication, socialization, and self-expression that may result in dysfunctional behavioral, cognitive, and emotional responses. Therapeutic music offers a noninvasive approach to strengthen these skills and effect behavior change. At a regional inpatient psychiatric hospital in Colorado, a program of therapeutic music was developed using Rogers' theory of unitary human beings as the theoretical framework. This article describes the approach used to strengthen coping skills in communication, socialization, and self-expression. Suggestions are made for developing a program of music with similar patient populations.

Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

PubMed Central

Martins-Marques, Tania; Pinho, Maria Joao; Zuzarte, Monica; Oliveira, Carla; Pereira, Paulo; Sluijter, Joost P. G.; Gomes, Celia; Girao, Henrique

2016-01-01

Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43) in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects. PMID:27702427

Allergen-specific immunotherapy: from therapeutic vaccines to prophylactic approaches

PubMed Central

Valenta, R.; Campana, R.; Marth, K.; van Hage, M.

2015-01-01

Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only disease-modifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease. PMID:22640224

[Therapeutic education for recurrent depressive disorder].

PubMed

Carde, Soufiane; Hatif, Séverine; Samama, Diane; Charbonnel, Patricia; Jouvent, Roland

2016-01-01

Depression is a serious and recurrent condition which can become chronic. As a complement to other therapeutic approaches, therapeutic patient education (TPE) or psychoeducation is effective. TPE groups led by a multidisciplinary hospitalisation team in a psychiatric department are thereby integrated into the global care in order to reduce relapses and improve patients' quality of life. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2013-09-01

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

MicroRNA therapeutics in cardiovascular medicine

PubMed Central

Thum, Thomas

2012-01-01

Cardiovascular diseases are the most common causes of human morbidity and mortality despite significant therapeutic improvements by surgical, interventional and pharmacological approaches in the last decade. MicroRNAs (miRNAs) are important and powerful mediators in a wide range of diseases and thus emerged as interesting new drug targets. An array of animal and even human miRNA-based therapeutic studies has been performed, which validate miRNAs as being successfully targetable to treat a wide range of diseases. Here, the current knowledge about miRNAs therapeutics in cardiovascular diseases on their way to clinical use are reviewed and discussed. PMID:22162462

Emerging Therapeutics for Advanced Thyroid Malignancies: Rationale and Targeted Approaches

PubMed Central

Harris, Pamela; Bible, Keith C.

2011-01-01

Introduction Thyroid cancer is an emerging public health concern. In the U.S., its incidence has doubled in the past decade, making it the 8th most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Areas covered Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Expert opinion Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity modulated radiation therapy appears to extend survival for patients with locoregionally-confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes. PMID:21910667

Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

PubMed Central

Brai, Annalaura; Fazi, Roberta; Tintori, Cristina; Zamperini, Claudio; Bugli, Francesca; Sanguinetti, Maurizio; Stigliano, Egidio; Esté, José; Badia, Roger; Franco, Sandra; Martinez, Javier P.; Meyerhans, Andreas; Saladini, Francesco; Zazzi, Maurizio; Garbelli, Anna; Botta, Maurizio

2016-01-01

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target. PMID:27118832

Nelson Syndrome: Update on Therapeutic Approaches.

PubMed

Azad, Tej D; Veeravagu, Anand; Kumar, Sunny; Katznelson, Laurence

2015-06-01

To review the pathophysiology and therapeutic modalities availble for Nelson syndrome. We reviewed the current literature including managment for Nelson syndrome. For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS. An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Current Status of Gene Engineering Cell Therapeutics

PubMed Central

Saudemont, Aurore; Jespers, Laurent; Clay, Timothy

2018-01-01

Ex vivo manipulations of autologous patient’s cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to induce tolerance and regulate inflammation. Here, we review the latest gene-engineered cell therapeutic approaches being currently explored to induce an efficient immune response against cancer cells or viruses by engineering T cells, natural killer cells, gamma delta T cells, or cytokine-induced killer cells and to modulate inflammation using regulatory T cells. PMID:29459866

ACHIEVING THE PROMISE OF THERAPEUTIC EXTRACELLULAR VESICLES: THE DEVIL IS IN DETAILS OF THERAPEUTIC LOADING

PubMed Central

Sutaria, Dhruvitkumar S.; Badawi, Mohamed; Phelps, Mitch A.; Schmittgen, Thomas D.

2017-01-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics. PMID:28315083

Nanotechnology based approaches in cancer therapeutics

NASA Astrophysics Data System (ADS)

Kumer Biswas, Amit; Reazul Islam, Md; Sadek Choudhury, Zahid; Mostafa, Asif; Fahim Kadir, Mohammad

2014-12-01

The current decades are marked not by the development of new molecules for the cure of various diseases but rather the development of new delivery methods for optimum treatment outcome. Nanomedicine is perhaps playing the biggest role in this concern. Nanomedicine offers numerous advantages over conventional drug delivery approaches and is particularly the hot topic in anticancer research. Nanoparticles (NPs) have many unique criteria that enable them to be incorporated in anticancer therapy. This topical review aims to look at the properties and various forms of NPs and their use in anticancer treatment, recent development of the process of identifying new delivery approaches as well as progress in clinical trials with these newer approaches. Although the outcome of cancer therapy can be increased using nanomedicine there are still many disadvantages of using this approach. We aim to discuss all these issues in this review.

[Therapeutic touch and anorexia nervosa].

PubMed

Satori, Nadine

2016-01-01

An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. Copyright © 2016. Published by Elsevier Masson SAS.

4D laser camera for accurate patient positioning, collision avoidance, image fusion and adaptive approaches during diagnostic and therapeutic procedures.

PubMed

Brahme, Anders; Nyman, Peter; Skatt, Björn

2008-05-01

A four-dimensional (4D) laser camera (LC) has been developed for accurate patient imaging in diagnostic and therapeutic radiology. A complementary metal-oxide semiconductor camera images the intersection of a scanned fan shaped laser beam with the surface of the patient and allows real time recording of movements in a three-dimensional (3D) or four-dimensional (4D) format (3D +time). The LC system was first designed as an accurate patient setup tool during diagnostic and therapeutic applications but was found to be of much wider applicability as a general 4D photon "tag" for the surface of the patient in different clinical procedures. It is presently used as a 3D or 4D optical benchmark or tag for accurate delineation of the patient surface as demonstrated for patient auto setup, breathing and heart motion detection. Furthermore, its future potential applications in gating, adaptive therapy, 3D or 4D image fusion between most imaging modalities and image processing are discussed. It is shown that the LC system has a geometrical resolution of about 0, 1 mm and that the rigid body repositioning accuracy is about 0, 5 mm below 20 mm displacements, 1 mm below 40 mm and better than 2 mm at 70 mm. This indicates a slight need for repeated repositioning when the initial error is larger than about 50 mm. The positioning accuracy with standard patient setup procedures for prostate cancer at Karolinska was found to be about 5-6 mm when independently measured using the LC system. The system was found valuable for positron emission tomography-computed tomography (PET-CT) in vivo tumor and dose delivery imaging where it potentially may allow effective correction for breathing artifacts in 4D PET-CT and image fusion with lymph node atlases for accurate target volume definition in oncology. With a LC system in all imaging and radiation therapy rooms, auto setup during repeated diagnostic and therapeutic procedures may save around 5 min per session, increase accuracy and allow

Oligonucleotide therapeutics in neurodegenerative diseases.

PubMed

Scoles, Daniel R; Pulst, Stefan M

2018-03-21

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.

Insomnia in childhood and adolescence: clinical aspects, diagnosis, and therapeutic approach.

PubMed

Nunes, Magda Lahorgue; Bruni, Oliviero

2015-01-01

To review the clinical characteristics, comorbidities, and management of insomnia in childhood and adolescence. This was a non-systematic literature review carried out in the PubMed database, from where articles published in the last five years were selected, using the key word "insomnia" and the pediatric age group filter. Additionally, the study also included articles and classic textbooks of the literature on the subject. During childhood, there is a predominance of behavioral insomnia as a form of sleep-onset association disorder (SOAD) and/or limit-setting sleep disorder. Adolescent insomnia is more associated with sleep hygiene problems and delayed sleep phase. Psychiatric (anxiety, depression) or neurodevelopmental disorders (attention deficit disorder, autism, epilepsy) frequently occur in association with or as a comorbidity of insomnia. Insomnia complaints in children and adolescents should be taken into account and appropriately investigated by the pediatrician, considering the association with several comorbidities, which must also be diagnosed. The main causes of insomnia and triggering factors vary according to age and development level. The therapeutic approach must include sleep hygiene and behavioral techniques and, in individual cases, pharmacological treatment. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Swimming in Ireland: Immersions in therapeutic blue space.

PubMed

Foley, Ronan

2015-09-01

This paper explores swimming as a healthy body-water engagement in blue space at selected outdoor Irish swimming spots. Associated theoretical underpinnings draw from non-representational theories (NRT). Taking as a starting point the idea of immersion, the paper argues for a deeper application of NRT to blue space settings. In addition, the paper reflects recent therapeutic geographies research on differential experiences of health and wellbeing linked to such immersions. Methodologically, the paper uses observer participation and swimmer's own voices to draw affective and embodied accounts from on and within water. The act of swimming as an emplaced and performed therapeutic encounter is highlighted along with a more critical discussion of contested narratives associated with risk and respect. Theoretical learning suggests the need for greater attention to the production of affect from across the life-course and a fuller articulation of the in-betweenness of theory and empirical testimonies. Swimming emerges from the study as a potentially valuable health and wellbeing resource that can be more fully harnessed to inform wider public health policy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Therapeutic Targets for Management of Periodontitis and Diabetes

PubMed Central

Sima, Corneliu; Van Dyke, Thomas E.

2016-01-01

The increasing incidence of diabetes mellitus (DM) and chronic periodontitis (CP) worldwide imposes a rethinking of individualized therapy for patients with both conditions. Central to bidirectional links between DM and CP is deregulated systemic inflammation and dysfunctional immune responses to altered-self and non-self. Control of blood glucose levels and metabolic imbalances associated with hyperglycemia in DM, and disruption of pathogenic subgingival biofilms in CP are currently the main therapeutic approaches for these conditions. Mounting evidence suggests the need to integrate immune modulatory therapeutics in treatment regimens that address the unresolved inflammation associated with DM and CP. The current review discusses the pathogenesis of DM and CP with emphasis on deregulated inflammation, current therapeutic approaches and the novel pro-resolution lipid mediators derived from n-3 polyunsaturated fatty acids. PMID:26881443

Therapeutic Targets for Management of Periodontitis and Diabetes

PubMed Central

Sima, Corneliu; Van Dyke, Thomas E.

2016-01-01

The increasing incidence of diabetes mellitus (DM) and chronic periodontitis (CP) worldwide imposes a rethinking of individualized therapy for patients with both conditions. Central to bidirectional links between DM and CP is deregulated systemic inflammation and dysfunctional immune responses to altered-self and non-self. Control of blood glucose levels and metabolic imbalances associated with hyperglycemia in DM, and disruption of pathogenic subgingival biofilms in CP are currently the main therapeutic approaches for these conditions. Mounting evidence suggests the need to integrate immune modulatory therapeutics in treatment regimens that address the unresolved inflammation associated with DM and CP. The current review discusses the pathogenesis of DM and CP with emphasis on deregulated inflammation, current therapeutic approaches and the novel pro-resolution lipid mediators derived from Ω-3 polyunsaturated fatty acids.

Life on the line: the therapeutic potentials of computer-mediated conversation.

PubMed

Miller, J K; Gergen, K J

1998-04-01

In what ways are computer networking practices comparable to face-to-face therapy? With the exponential increase in computer-mediated communication and the increasing numbers of people joining topically based computer networks, the potential for grass-roots therapeutic (or antitherapeutic) interchange is greatly augmented. Here we report the results of research into exchanges on an electronic bulletin board devoted to the topic of suicide. Over an 11-month period participants offered each other valuable resources in terms of validation of experience, sympathy, acceptance, and encouragement. They also asked provocative questions and furnished broad-ranging advice. Hostile entries were rare. However, there were few communiques that parallel the change-inducing practices more frequent within many therapeutic settings. In effect, on-line dialogues seemed more sustaining than transforming. Further limits and potentials of on-line communication are explored.

Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

NASA Astrophysics Data System (ADS)

Chen, Kuan-Ju

Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches.

PubMed

Reid, Andrew T; Veerati, Punnam Chander; Gosens, Reinoud; Bartlett, Nathan W; Wark, Peter A; Grainge, Chris L; Stick, Stephen M; Kicic, Anthony; Moheimani, Fatemeh; Hansbro, Philip M; Knight, Darryl A

2018-05-01

Dysregulated induction of goblet cell differentiation results in excessive production and retention of mucus and is a common feature of several chronic airways diseases. To date, therapeutic strategies to reduce mucus accumulation have focused primarily on altering the properties of the mucus itself, or have aimed to limit the production of mucus-stimulating cytokines. Here we review the current knowledge of key molecular pathways that are dysregulated during persistent goblet cell differentiation and highlights both pre-existing and novel therapeutic strategies to combat this pathology. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

[Diagnostic and Therapeutic Approach of Chronic Spontaneous Urticaria: Recommendations in Portugal].

PubMed

Costa, Célia; Gonçalo, Margarida

2016-11-01

Chronic spontaneous urticaria is a complex disorder, of unclear etiology, easily diagnosed although often difficult to treat. It has a significant impact on the patients' quality of life and results in high direct and indirect costs. The diagnosis of chronic spontaneous urticaria is mainly clinical and a limited number of tests is recommended for differential diagnosis and/or for the investigation/exclusion of possible causes. In addition to the complete blood count and C-reactive protein, and/or erythrocyte sedimentation rate, additional tests must be selected according to clinical criteria. The aim of therapy is the complete clinical control of chronic spontaneous urticaria. Evolution should be documented by weekly symptom scoring - Weekly Urticaria Activity Score (UAS7) -, as well as the assessment of quality of life. The therapeutic approach is based on second-generation H1 antihistamines (anti-H1) administered continuously in the approved doses (first line), and, in the absence of a clinical response, up to four times the daily-approved dose (second line). First generation H1 antihistamines are not recommended. Approximately 30% of patients are not controlled with second line therapy, and it is recommended to add a third line therapy. Of the two options, omalizumab and cyclosporine, only omalizumab is approved for chronic spontaneous urticaria and has a better safety profile, thus being preferably recommended. In Portugal there are no national-based recommendations applicable to clinical practice. The elaboration of these recommendations is justified by the need to standardize both the diagnosis and the treatment approach of patients with chronic spontaneous urticaria in Portugal, and for the referral of patients to specialized centers, in the most severe cases.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches.

PubMed

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D'Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches

PubMed Central

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D’Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice. PMID:28083535

[Diagnostic and therapeutic use of human anti-D (Rho) monoclonal antibodies. Evaluation and perspectives].

PubMed

Rouger, P; Goossens, D; Champomier, F; Tsikas, G; Liberge, G; Leblanc, J; Richard, C; Bailleul, C; Salmon, C

1985-12-01

Human monoclonal antibodies will be essential in medicine. They are valuable tools for biological diagnosis and therapeutics. Our model, human monoclonal antibodies directed against the Rhesus D antigen can be used for the determination of the Rhesus D phenotype and for the suppression of Rh(D) immunisation in women. These new products require new procedures of preparation, new regulations for the quality controls, which will be discussed in this paper.

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2014-09-01

our animal vendor, Charles River Laboratories (CRL), to adopt their intrathecal catheterization service for this purpose. Cannulated animals from CRL...pilot “idea” study. Thus, both experimental approaches, catheterization did not allow us to obtain statistically significant therapeutic efficacy...fluid, which will help developing new approaches for delivery of therapies, in particular biopharmaceuticals, to the central nervous system and

Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications.

PubMed

Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

2014-02-21

A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications

NASA Astrophysics Data System (ADS)

Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

2014-01-01

A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

Comparison of microCT and an inverse finite element approach for biomechanical analysis: Results in a MSC therapeutic system for fracture healing

PubMed Central

Weis, Jared A.; Granero-Moltó, Froilán; Myers, Timothy J.; Longobardi, Lara; Spagnoli, Anna; Miga, Michael I.

2013-01-01

An important concern in the study of fracture healing is the ability to assess mechanical integrity in response to candidate therapeutics in small-animal systems. In recent reports, it has been proposed that microCT image-derived densitometric parameters could be used as a surrogate for mechanical property assessment. Recently, we have proposed an inverse methodology that iteratively reconstructs the modulus of elasticity of the lumped soft callus/hard callus region by integrating both intrinsic mechanical property (from biomechanical testing) and geometrical information (from microCT) within an inverse finite element analysis (FEA) to define a callus quality measure. In this paper, data from a therapeutic system involving mesenchymal stem cells is analyzed within the context of comparing traditional microCT densitometric and mechanical property metrics. In addition, a novel multi-parameter regression microCT parameter is analyzed as well as our inverse FEA metric. The results demonstrate that the inverse FEA approach was the only metric to successfully detect both longitudinal and therapeutic responses. While the most promising microCT-based metrics were adequate at early healing states, they failed to track late-stage mechanical integrity. In addition, our analysis added insight to the role of MSCs by demonstrating accelerated healing and was the only metric to demonstrate therapeutic benefits at late-stage healing. In conclusion, the work presented here indicates that microCT densitometric parameters are an incomplete surrogate for mechanical integrity. Additionally, our inverse FEA approach is shown to be very sensitive and may provide a first-step towards normalizing the often challenging process of assessing mechanical integrity of healing fractures. PMID:22766379

New Therapeutic Approaches for Waldenstrom Macroglobulinemia

PubMed Central

Stedman, Jennifer; Roccaro, Aldo; Leleu, Xavier; Ghobrial, Irene M.

2011-01-01

Waldenstrom Macroglobulinemia (WM) is a B-cell disorder characterized by the infiltration of the bone marrow (BM) with lymphoplasmacytic cells, as well as detection of an IgM monoclonal gammopathy in the serum. WM is an incurable disease, with an overall medial survival of only 5-6 years. First-line therapy of WM has been based on single-agent or combination therapy with alkylator agents (e.g. chlorambucil or cyclophasphamide), nucleoside analogues (cladribine or fludarabine), and the monoclonal antibody rituximab. Novel therapeutic agents that have demonstrated efficacy in WM include thalidomide, lenalidomide, bortezomib, everolimus, Atacicept, and perifosine. The range of the ORR to these agents is between 25-80%. Ongoing and planned future clinical trials include those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as panobinostat, humanized CD20 antibodies such as Ofatumumab, and additional alkylating agents such as bendamustine. These agents, when compared to traditional chemotherapeutic agents, may lead in the future to higher responses, longer remissions and better quality of life for patients with WM. PMID:21869855

Cognition As a Therapeutic Target in the Suicidal Patient Approach

PubMed Central

da Silva, Antônio Geraldo; Malloy-Diniz, Leandro Fernandes; Garcia, Marina Saraiva; Figueiredo, Carlos Guilherme Silva; Figueiredo, Renata Nayara; Diaz, Alexandre Paim; Palha, António Pacheco

2018-01-01

The current considerations about completed suicides and suicide attempts in different cultures call the attention of professionals to this serious public health problem. Integrative approaches have shown that the confluence of multiple biological and social factors modulate various psychopathologies and dysfunctional behaviors, such as suicidal behavior. Considering the level of intermediate analysis, personality traits and cognitive functioning are also of great importance for understanding the suicide phenomenon. About cognitive factors, we can group them into cognitive schemas of reality interpretation and underlying cognitive processes. On the other hand, different types of primary cognitive alterations are related to suicidal behavior, especially those resulting from changes in frontostriatal circuits. Among such cognitive mechanisms can be highlighted the attentional bias for environmental cues related to suicide, impulsive behavior, verbal fluency deficits, non-adaptive decision-making, and reduced planning skills. Attentional bias consists in the effect of thoughts and emotions, frequently not conscious, about the perception of environmental stimuli. Suicidal ideation and hopelessness can make the patient unable to find alternative solutions to their problems other than suicide, biasing their attention to environmental cues related to such behavior. Recent research efforts are directed to assess the possible use of attention bias as a therapeutic target in patients presenting suicide behavior. The relationship between impulsivity and suicide has been largely investigated over the last decades, and there is still controversy about the theme. Although there is strong evidence linking impulsivity to suicide attempts. Effective interventions address to reduce impulsivity in clinical populations at higher risk for suicide could help in the prevention. Deficits in problem-solving ability also seem to be distorted in patients who attempt suicide. Understanding

Contact refusal by children following acrimonious separation: therapeutic approaches with children and parents.

PubMed

Dejong, Margaret; Davies, Hilary

2013-04-01

This paper aims to build on the existing literature, by presenting some thoughts based on clinical experience with nine families of children referred for intractable contact refusal with one parent following marital separation. This particular group of high-conflict divorce cases engenders an inordinate amount of frustration both within the courts and therapeutic agencies. We outline here our assessment process and therapeutic strategies, as well as consideration of the role of the wider professional system and the courts. We conclude that whether or not direct contact with the rejected parent is achieved, useful therapeutic work can be carried out to assist children in moving on with their lives.

Laminin Receptor-Avid Nanotherapeutic EGCg-AuNPs as a Potential Alternative Therapeutic Approach to Prevent Restenosis

PubMed Central

Khoobchandani, Menka; Katti, Kavita; Maxwell, Adam; Fay, William P.; Katti, Kattesh V.

2016-01-01

In our efforts to develop new approaches to treat and prevent human vascular diseases, we report herein our results on the proliferation and migration of human smooth muscles cells (SMCs) and endothelial cells (ECs) using epigallocatechin-3-gallate conjugated gold nanoparticles (EGCg-AuNPs) as possible alternatives to drug coated stents. Detailed in vitro stability studies of EGCg-AuNPs in various biological fluids, affinity and selectivity towards SMCs and ECs have been investigated. The EGCg-AuNPs showed selective inhibitory efficacy toward the migration of SMCs. However, the endothelial cells remained unaffected under similar experimental conditions. The cellular internalization studies have indicated that EGCg-AuNPs internalize into the SMCs and ECs within short periods of time through laminin receptor mediated endocytosis mode. Favorable toxicity profiles and selective affinity toward SMCs and ECs suggest that EGCg-AuNPs may provide attractive alternatives to drug coated stents and therefore offer new therapeutic approaches in treating cardiovascular diseases. PMID:26938531

IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

DTIC Science & Technology

2013-02-01

therapies (surgery, radiation and chemotherapy) have reached a therapeutic ceiling in improving the five- year overall survival rate of non-small cell...poor understanding of the disease and its resistance to the therapy . Lung cancer is a heterogeneous disease, resulting from accumulated genetic... a new promising approach to treatment of lung cancer. The program project IMPACT has proposed to integrate targeted therapy in the lung cancer

Therapeutic Doll Making in Art Psychotherapy for Complex Trauma

ERIC Educational Resources Information Center

Stace, Sonia M.

2014-01-01

Therapeutic doll making can hold diverse functions for clients in therapy, particularly for those clients who are working through complex trauma histories. Recent literature pertaining to the treatment of complex trauma suggests that talking treatments have their limits; supplementary therapeutic approaches that focus on sensory, physical,…

Teachers Talking about Writing Assessment: Valuable Professional Learning?

ERIC Educational Resources Information Center

Reid, Lesley

2007-01-01

This article argues that the engagement of teachers in collaborative discussions about assessment can provide a fruitful context for valuable professional learning. It is of interest to those who provide Continuous Professional Development (CPD) opportunities for teachers and teachers themselves. It looks particularly at the value of writing…

How to Implement Therapeutic Evaluative Conditioning in a Clinical Setting.

PubMed

Franklin, Joseph C; Fox, Kathryn R; Ribeiro, Jessica D

2017-05-01

Self-injurious behaviors (SIBs), including both suicidal and nonsuicidal self-injury, are major public health problems that have been on the rise in recent decades. There are few effective SIB interventions, and those that are effective cannot reach most people who are in need of help-that is, these interventions are not scalable. To address this need, we recently developed a scalable, app-based treatment called Therapeutic Evaluative Conditioning (TEC) that preliminary studies have shown causes reductions in SIBs (Franklin et al., 2016). Although TEC was developed and evaluated as a standalone, self-administered intervention, it may also be a valuable therapeutic tool within traditional clinical settings. Here we provide a case illustration of a young adult female who presented at an outpatient clinic with a long history of self-injurious behaviors and multiple failed treatment attempts. In discussing this case, we describe how to implement TEC within such a setting and what might be expected as a result. © 2017 Wiley Periodicals, Inc.

Therapeutic interventions in sepsis: current and anticipated pharmacological agents

PubMed Central

Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

2014-01-01

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

New diagnostic and therapeutic approach to thyroid-associated orbitopathy based on applied kinesiology and homeopathic therapy.

PubMed

Moncayo, Roy; Moncayo, Helga; Ulmer, Hanno; Kainz, Hartmann

2004-08-01

To investigate pathogenetic mechanisms related to the lacrimal and lymphatic glands in patients with thyroid-associated orbitopathy (TAO), and the potential of applied kinesiology diagnosis and homeopathic therapeutic measures. Prospective. Thyroid outpatient unit and a specialized center for complementary medicine (WOMED, Innsbruck; R.M. and H.M.). Thirty-two (32) patients with TAO, 23 with a long-standing disease, and 9 showing discrete initial changes. All patients were euthyroid at the time of the investigation. Clinical investigation was done, using applied kinesiology methods. Departing from normal reacting muscles, both target organs as well as therapeutic measures were tested. Affected organs will produce a therapy localization (TL) that turns a normal muscle tone weak. Using the same approach, specific counteracting therapies (i.e., tonsillitis nosode and lymph mobilizing agents) were tested. Change of lid swelling, of ocular movement discomfort, ocular lock, tonsil reactivity and Traditional Chinese Medicine criteria including tenderness of San Yin Jiao (SP6) and tongue diagnosis were recorded in a graded fashion. Positive TL reactions were found in the submandibular tonsillar structures, the pharyngeal tonsils, the San Yin Jiao point, the lacrimal gland, and with the functional ocular lock test. Both Lymphdiaral (Pascoe, Giessen, Germany) and the homeopathic preparation chronic tonsillitis nosode at a C3 potency (Spagyra, Grödig, Austria) counteracted these changes. Both agents were used therapeutically over 3-6 months, after which all relevant parameters showed improvement. Our study demonstrates the involvement of lymphatic structures and flow in the pathogenesis of TAO. The tenderness of the San Yin Jiao point correlates to the above mentioned changes and should be included in the clinical evaluation of these patients.

Renal denervation: a new therapeutic approach for resistant hypertension.

PubMed

Cao, Longxing; Fu, Qiang; Wang, Binghui; Li, Zhiliang

2014-01-01

To review the advances in studies on renal denervation. References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Articles with keywords "renal denervation" and "resistant hypertension" were selected. Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

Oncolytic Viruses: Therapeutics With an Identity Crisis.

PubMed

Breitbach, Caroline J; Lichty, Brian D; Bell, John C

2016-07-01

Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

New Therapies Offer Valuable Options for Patients with Melanoma

Cancer.gov

Two phase III clinical trials of new therapies for patients with metastatic melanoma presented in June at the 2011 ASCO conference confirmed that vemurafenib and ipilimumab (Yervoy™) offer valuable new options for the disease.

Therapeutic targeting of replicative immortality

PubMed Central

Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S. Salman; Nowsheen, Somaira; Yang, Xujuan

2015-01-01

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

A systematic review study of therapeutic effects of Matricaria recuitta chamomile (chamomile)

PubMed Central

Miraj, Sepide; Alesaeidi, Samira

2016-01-01

Introduction Matricaria recuitta chamomilla is a plant that grows and is cultivated in some parts of Iran. The aim of this study was to overview the therapeutic effects of this valuable plant. This systematic review was aimed to introduce Matricaria recuitta chamomile, its chemical compounds, and its traditional usages. Methods This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified about 87 references. In this study, 69 studies were accepted for further screening and met all our inclusion criteria [in English, full text, therapeutic effects of Matricaria recuitta chamomilla L and dated mainly from the year 1990 to 2016]. The search terms were “Matricaria recuitta chamomilla L.,” “therapeutic properties,” “pharmacological effects.” Result It is commonly used for its antioxidant, antimicrobial, antidepressant, anti-inflammatory, antidiarrheal activities, angiogenesis activity, anticarcinogenic, hepatoprotective, and antidiabetic effects. Besides, it is beneficial for knee osteoarthritis, ulcerative colitis, premenstrual syndrome, and gastrointestinal disorders. Conclusion Matricaria recuitta chamomilla L. is widely used for therapeutic and nontherapeutic purposes that trigger its significant value. Various combinations and numerous medicinal properties of its extract, oil, and leaves demand further studies about other useful and unknown properties of this multipurpose plant. PMID:27790360

Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development.

PubMed

Salazar-Fontana, Laura I; Desai, Dharmesh D; Khan, Tarik A; Pillutla, Renuka C; Prior, Sandra; Ramakrishnan, Radha; Schneider, Jennifer; Joseph, Alexandra

2017-03-01

All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.

Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach.

PubMed

Srinivasan, Venkataramanujam; Ahmad, Asma H; Mohamed, Mahaneem; Zakaria, Rahimah

2012-05-01

Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin

[Clinical presentation, therapeutic approach and outcomes in acute poisoning treated with activated charcoal. Are there differences between men and women?].

PubMed

Amigó-Tadín, Montserrat; Nogué-Xarau, Santiago; Miró-Andreu, Oscar

2010-01-01

To determine whether there are gender-based differences in the clinical presentation, therapeutic approaches and outcomes in acute poisoning treated with activated charcoal. A descriptive study conducted in the Emergency Department of the Hospital Clínic de Barcelona over the 7 years between the years 2001 and 2008. The study included poisoned patients who had received activated charcoal. The variables included, epidemiological data, clinical and toxicological presentation, therapeutic approach, time in emergency department and outcomes. A total of 575 patients were included in the study. The mean age was 37.8 (SD 14.8) years and 65.7% were females. No differences were observed between males and females with respect to age, number of drugs involved in the poisoning or the number of tablets ingested, but a higher prevalence of benzodiazepine poisoning was observed in females compared to males (69.8 vs. 61.2%; P<0.05). Alcohol combined with drug poisoning was more common in males than in females (32.4 vs.18.8%; P<0.001). Administration of activated charcoal in non-drug poisoning was also more common in males than in females (7.9 vs. 3.2%; P<0.05). There were no differences between genders as regards clinical presentation of the poisonings, delays in care, hours of emergency department stay, treatment or outcome. Benzodiazepine poisoning was more prevalent in females than in males. Non-drug poisonings and alcohol combined with drug ingestion were more common in males. The clinical outcomes of the poisonings, delays in care, therapeutic requirements and admissions were similar between genders. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Advances in sarcoma genomics and new therapeutic targets

PubMed Central

Taylor, Barry S.; Barretina, Jordi; Maki, Robert G.; Antonescu, Cristina R.; Singer, Samuel; Ladanyi, Marc

2012-01-01

Preface Increasingly, human mesenchymal malignancies are classified by the abnormalities that drive their pathogenesis. While many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities and in many cases are resistant to adjuvant therapies. In this Review, we discuss the core molecular determinants of sarcomagenesis and emphasize the emerging genomic and functional genetic approaches that, coupled to novel therapeutic strategies, have the potential to transform the care of patients with sarcoma. PMID:21753790

Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity.

PubMed

Carlucci, Christian; Petrof, Elaine O; Allen-Vercoe, Emma

2016-11-01

The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Recommendations Concerning the Therapeutic Approach to Immunocompromised Children With Tuberculosis.

PubMed

Lancella, Laura; Galli, Luisa; Chiappini, Elena; Montagnani, Carlotta; Gabiano, Clara; Garazzino, Silvia; Principi, Nicola; Tadolini, Marina; Matteelli, Alberto; Battista Migliori, Giovanni; Villani, Alberto; de Martino, Maurizio; Esposito, Susanna

2016-01-01

This article describes the recommendations of a group of scientific societies concerning the therapeutic approach to immunocompromised children with tuberculosis (TB). Using the Consensus Conference method, relevant publications in English were identified by a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until December 31, 2014. On the basis of their clinical experience and the published evidence, the group of experts concluded that, although immunosuppressed subjects are at greater risk of developing TB, none of the signs or symptoms is sensitive or specific enough to enable a diagnosis. Immunocompromised patients are at greater risk of developing extrapulmonary forms of TB, especially if they are adolescents, whereas pulmonary forms are more prevalent among younger patients. When TB is suspected, a combination of skin and immunologic tests and other clinical, radiologic, and microbiologic examinations can be used to assess the risk of infection or disease. If the TB diagnosis is confirmed, immunocompromised children should be treated by using a standard regimen with a minimum of 4 drugs for at least 9 to 12 months, during which the tolerability of the drugs and their interactions should be carefully evaluated. It is difficult to diagnose and treat TB in immunocompromised children. Thus, all pediatric patients undergoing immunosuppressive therapy who develop TB should be diagnosed and treated at a TB reference center, which should also be responsible for the recommended follow-up. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

[Pancreatic pseudocyst in children: what is the best therapeutic approach?].

PubMed

Nouira, F; Ben Ahmed, Y; Sarrai, N; Ghorbel, S; Jlidi, S; Chaouachi, B

2011-11-01

Pancreatic pseudocyst is an uncommon disorder in children and the majority of reported cases are secondary to trauma. Treatment options range from medical management to different forms of drainage procedure. The aim of this study was to discuss therapeutic strategies. The authors report herein pancreatic pseudocyst in four children aged 7, 9, 12, and 13 years with non-resolving pancreatic pseudocyst over a 2-year period from January 2006 to July 2008. The etiology of pancreatic pseudocyst was abdominal trauma in two cases and acute pancreatitis in two cases. Ultrasound and computed tomography scans confirmed the diagnosis. Two patients had endoscopic drainage. There were no procedure-related complications, nor was there a recurrence of the cyst. In one case, the pancreatic pseudocyst resolved spontaneously. This report suggests that children with non-spontaneously resolving pancreatic pseudocyst can be treated successfully and safely with endoscopic drainage. Surgical treatment remains an important alternative in the therapeutic armamentarium of this affection. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Return to Competition in a Chronic Low Back Pain Runner: Beyond a Therapeutic Exercise Approach, a Case Report.

PubMed

Veneziani, Sergio; Doria, Christian; Falciati, Luca; Castelli, Claudio Carlo; Illic, Giorgio Fanò

2014-09-23

Chronic low back pain (CLBP) is a disabling condition affecting both quality of life and performance in athletes. Several approaches have been proposed in the field of physiotherapy, manual therapy, physical exercise and counseling. None apparently is outdoing the other with the exception of trunk stability exercises in specific conditions. The present paper describes a clinical success in managing a CLBP runner affected by MRI documented disk herniation via dietary change. Dietary changes allowed our patient that had failed with previous standard therapeutic approaches, to regain an optimal pain-free condition. We advance the hypothesis that a visceral-autonomic concomitant or primary disturbance possibly generating mild gastrointestinal discomfort in CLBP patients should be ruled out as a possible cause of pain and disability at the somato-motor level.

Therapeutic approach to malnutrition and sarcopenia.

PubMed

Burgos Peláez, Rosa

2012-01-01

Sarcopenia is a syndrome characterized by the progressive loss of muscle mass and strength with a risk of undesirable effects such as physical disability, poor quality of life and death, and it is a major contributing factor of disability and loss of independence in the elderly. Its etiopathogenics include different mechanisms that are both intrinsic to the muscle itself and related to changes in the central nervous system, as well as hormonal and lifestyle factors. Several hormones and cytokines affect muscle function and mass. The reduction in testosterone and estrogens associated with ageing speeds up the loss of muscle mass. Growth hormone is also involved in the loss of lean body mass. Although sarcopenia does not completely revert with exercise, the absence of physical activity accelerates muscle mass loss. Diagnosing sarcopenia is hindered by a lack of reliable methods for measuring muscle mass. Different strategies have been tested for its treatment: testosterone replacement therapy/other anabolic androgens, estrogens in women, growth hormone, nutritional treatment and exercise. Of all the therapeutic options available, only resistance training with or without nutritional supplementation has shown its efficacy in increasing skeletal muscle mass. Copyright © 2012 S. Karger AG, Basel.

Double-balloon enteroscopy: Indications, approaches, diagnostic and therapeutic yield, and safety. Early experience at a single center.

PubMed

García-Correa, J J E; Ramírez-García, J J; García-Contreras, L F; Fuentes-Orozco, C; Irusteta-Jiménez, L; Michel-Espinoza, L R; Carballo Uribe, A S; Torres Chávez, J A; González-Ojeda, A

Double-balloon enteroscopy has been improving the visualization of the entire intestine for more than a decade. It is a complementary method in the study of intestinal diseases that enables biopsies to be taken and treatments to be administered. Our aim was to describe its main indications, insertion routes, diagnostic/therapeutic yield, and complications. All patients referred to our unit with suspected small bowel pathology were included. The insertion route (oral/anal) was determined through diagnostic suspicion. The variables measured were: insertion route, small bowel examination extent, endoscopic diagnosis/treatment, biopsy/histopathology report, complications, and surgical findings. The study included 28 double-balloon enteroscopies performed on 23 patients, of which 10 were women and 13 were men (mean age of 52.95 years). The oral approach was the most widely used (n=21), the main indication was overt small bowel bleeding (n=16), and the general diagnostic yield was 65.21%. The therapeutic intervention rate was 39.1% and the procedure was effective in all the cases. The most widely used treatment was argon plasma therapy (n=7). The complication rate was 8.6%; one patient presented with low blood pressure due to active bleeding and another had deep mucosal laceration caused by the argon plasma. Double-balloon enteroscopy is a safe and efficacious method for the study and management of small bowel diseases, with an elevated diagnostic and therapeutic yield. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Chitosan and thiolated chitosan: Novel therapeutic approach for preventing corneal haze after chemical injuries.

PubMed

Zahir-Jouzdani, Forouhe; Mahbod, Mirgholamreza; Soleimani, Masoud; Vakhshiteh, Faezeh; Arefian, Ehsan; Shahosseini, Saeed; Dinarvand, Rasoul; Atyabi, Fatemeh

2018-01-01

Corneal haze, commonly caused by deep physical and chemical injuries, can greatly impair vision. Growth factors facilitate fibroblast proliferation and differentiation, which leads to haze intensity. In this study, the potential effect of chitosan (CS) and thiolated-chitosan (TCS) nanoparticles and solutions on inhibition of fibroblast proliferation, fibroblast to myofibroblast differentiation, neovascularization, extracellular matrix (ECM) deposition, and pro-fibrotic cytokine expression was examined. Transforming growth factor beta-1 (TGFβ 1 ) was induced by interleukin-6 (IL6) in human corneal fibroblasts and expression levels of TGFβ 1 , Platelet-derived growth factor (PDGF), α-smooth muscle actins (α-SMA), collagen type I (Col I), fibronectin (Fn) and vascular endothelial growth factor (VEGF) were quantified using qRT-PCR. To assess wound-healing capacity, TCS-treated mice were examined for α-SMA positive cells, collagen deposition, inflammatory cells and neovascularization through pathological immunohistochemistry. The results revealed that CS and TCS could down-regulate the expression levels of TGFβ 1 and PDGF comparable to that of TGFβ 1 knockdown experiment. However, down-regulation of TGFβ 1 was not regulated through miR29b induction. Neovascularization along with α-SMA and ECM deposition were significantly diminished. According to these findings, CS and TCS can be considered as potential anti-fibrotic and anti-angiogenic therapeutics. Furthermore, TCS, thiolated derivative of CS, will increase mucoadhesion of the polymer at the corneal surface which makes the polymer efficient and non-toxic therapeutic approach for corneal injuries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathogenic role for macrophage migration inhibitory factor in glioblastoma and its targeting with specific inhibitors as novel tailored therapeutic approach

PubMed Central

Mangano, Katia; Mazzon, Emanuela; Basile, Maria Sofia; Di Marco, Roberto; Bramanti, Placido; Mammana, Santa; Petralia, Maria Cristina; Fagone, Paolo; Nicoletti, Ferdinando

2018-01-01

Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine expressed by a variety of cell types. Although MIF has been primarily studied for its role in the pathogenesis of autoimmune diseases, it has also been shown to promote tumorigenesis and it is over expressed in various malignant tumors. MIF is able to induce angiogenesis, cell cycle progression, and to block apoptosis. As tailored therapeutic approaches for the inhibition of endogenous MIF are being developed, it is important to evaluate the role of MIF in individual neoplastic conditions that may benefit from specific MIF inhibitors. Along with this line, in this paper, we have reviewed the evidence of the involvement of MIF in the etiopathogenesis and progression of glioblastoma and the preclinical data suggesting the possible use of specific MIF inhibition as a potential novel therapeutic strategy for brain tumors. PMID:29707160

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

PubMed

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

2015-11-18

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

Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival

PubMed Central

2012-01-01

Background The current treatment regimen for glioma patients is surgery, followed by radiation therapy plus temozolomide (TMZ), followed by 6 months of adjuvant TMZ. Despite this aggressive treatment regimen, the overall survival of all surgically treated GBM patients remains dismal, and additional or different therapies are required. Depending on the cancer type, SPARC has been proposed both as a therapeutic target and as a therapeutic agent. In glioma, SPARC promotes invasion via upregulation of the p38 MAPK/MAPKAPK2/HSP27 signaling pathway, and promotes tumor cell survival by upregulating pAKT. As HSP27 and AKT interact to regulate the activity of each other, we determined whether inhibition of HSP27 was better than targeting SPARC as a therapeutic approach to inhibit both SPARC-induced glioma cell invasion and survival. Results Our studies found the following. 1) SPARC increases the expression of tumor cell pro-survival and pro-death protein signaling in balance, and, as a net result, tumor cell survival remains unchanged. 2) Suppressing SPARC increases tumor cell survival, indicating it is not a good therapeutic target. 3) Suppressing HSP27 decreases tumor cell survival in all gliomas, but is more effective in SPARC-expressing tumor cells due to the removal of HSP27 inhibition of SPARC-induced pro-apoptotic signaling. 4) Suppressing total AKT1/2 paradoxically enhanced tumor cell survival, indicating that AKT1 or 2 are poor therapeutic targets. 5) However, inhibiting pAKT suppresses tumor cell survival. 6) Inhibiting both HSP27 and pAKT synergistically decreases tumor cell survival. 7) There appears to be a complex feedback system between SPARC, HSP27, and AKT. 8) This interaction is likely influenced by PTEN status. With respect to chemosensitization, we found the following. 1) SPARC enhances pro-apoptotic signaling in cells exposed to TMZ. 2) Despite this enhanced signaling, SPARC protects cells against TMZ. 3) This protection can be reduced by inhibiting p

Therapeutic Approaches for Shankopathies

PubMed Central

Wang, Xiaoming; Bey, Alexandra; Chang, Leeyup; Krystal, Andrew D.; Jiang, Yong-hui

2013-01-01

Despite recent advances in understanding the molecular mechanisms of autism spectrum disorders (ASD), the current treatments for these disorders are mostly focused on behavioral and educational approaches. The considerable clinical and molecular heterogeneity of ASD present a significant challenge to the development of an effective treatment targeting underlying molecular defects. Deficiency of SHANK family genes causing ASD represent an exciting opportunity for developing molecular therapies because of strong genetic evidence for SHANKs as causative genes in ASD and the availability of a panel of Shank mutant mouse models. In this article we review the literature suggesting the potential for developing therapies based on molecular characteristics and discuss several exciting themes that are emerging from studying Shank mutant mice at the molecular level and in terms of synaptic function. PMID:23536326

Team-based Learning in Therapeutics Workshop Sessions

PubMed Central

Kelley, Katherine A.; Metzger, Anne H.; Bellebaum, Katherine L.; McAuley, James W.

2009-01-01

Objectives To implement team-based learning in the workshop portion of a pathophysiology and therapeutics sequence of courses to promote integration of concepts across the pharmacy curriculum, provide a consistent problem-solving approach to patient care, and determine the impact on student perceptions of professionalism and teamwork. Design Team-based learning was incorporated into the workshop portion of 3 of 6 pathophysiology and therapeutics courses. Assignments that promoted team-building and application of key concepts were created. Assessment Readiness assurance tests were used to assess individual and team understanding of course materials. Students consistently scored 20% higher on team assessments compared with individual assessments. Mean professionalism and teamwork scores were significantly higher after implementation of team-based learning; however, this improvement was not considered educationally significant. Approximately 91% of students felt team-based learning improved understanding of course materials and 93% of students felt teamwork should continue in workshops. Conclusion Team-based learning is an effective teaching method to ensure a consistent approach to problem-solving and curriculum integration in workshop sessions for a pathophysiology and therapeutics course sequence. PMID:19885069

Team-based learning in therapeutics workshop sessions.

PubMed

Beatty, Stuart J; Kelley, Katherine A; Metzger, Anne H; Bellebaum, Katherine L; McAuley, James W

2009-10-01

To implement team-based learning in the workshop portion of a pathophysiology and therapeutics sequence of courses to promote integration of concepts across the pharmacy curriculum, provide a consistent problem-solving approach to patient care, and determine the impact on student perceptions of professionalism and teamwork. Team-based learning was incorporated into the workshop portion of 3 of 6 pathophysiology and therapeutics courses. Assignments that promoted team-building and application of key concepts were created. Readiness assurance tests were used to assess individual and team understanding of course materials. Students consistently scored 20% higher on team assessments compared with individual assessments. Mean professionalism and teamwork scores were significantly higher after implementation of team-based learning; however, this improvement was not considered educationally significant. Approximately 91% of students felt team-based learning improved understanding of course materials and 93% of students felt teamwork should continue in workshops. Team-based learning is an effective teaching method to ensure a consistent approach to problem-solving and curriculum integration in workshop sessions for a pathophysiology and therapeutics course sequence.

Diffusion MRI in early cancer therapeutic response assessment

PubMed Central

Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

2016-01-01

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

Exploring Protein-Peptide Recognition Pathways Using a Supervised Molecular Dynamics Approach.

PubMed

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2017-04-04

Peptides have gained increased interest as therapeutic agents during recent years. The high specificity and relatively low toxicity of peptide drugs derive from their extremely tight binding to their targets. Indeed, understanding the molecular mechanism of protein-peptide recognition has important implications in the fields of biology, medicine, and pharmaceutical sciences. Even if crystallography and nuclear magnetic resonance are offering valuable atomic insights into the assembling of the protein-peptide complexes, the mechanism of their recognition and binding events remains largely unclear. In this work we report, for the first time, the use of a supervised molecular dynamics approach to explore the possible protein-peptide binding pathways within a timescale reduced up to three orders of magnitude compared with classical molecular dynamics. The better and faster understating of the protein-peptide recognition pathways could be very beneficial in enlarging the applicability of peptide-based drug design approaches in several biotechnological and pharmaceutical fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

A thermo-physical analysis of the proton pump vacuolar-ATPase: the constructal approach.

PubMed

Lucia, Umberto; Ponzetto, Antonio; Deisboeck, Thomas S

2014-10-24

Pumping protons across a membrane was a critical step at the origin of life on earth, and it is still performed in all living organisms, including in human cells. Proton pumping is paramount to keep normal cells alive, e.g. for lysosomal digestion and for preparing peptides for immune recognition, but it goes awry in cancer cells. They acidify their microenvironment hence membrane voltage is lowered, which in turn induces cell proliferation, a hallmark of cancer. Proton pumping is achieved by means of rotary motors, namely vacuolar ATPases (V-ATPase), which are present at many of the multiple cellular interfaces. Therefore, we undertook an examination of the thermodynamic properties of V-ATPases. The principal result is that the V-ATPase-mediated control of the cell membrane potential and the related and consequent environmental pH can potentially represent a valuable support strategy for anticancer therapies. A constructal theory approach is used as a new viewpoint to study how V-ATPase can be modulated for therapeutic purposes. In particular, V-ATPase can be regulated by using external fields, such as electromagnetic fields, and a theoretical approach has been introduced to quantify the appropriate field strength and frequency for this new adjuvant therapeutic strategy.

Therapeutic targeting of the p53 pathway in cancer stem cells

PubMed Central

Prabhu, Varun V.; Allen, Joshua E.; Hong, Bo; Zhang, Shengliang; Cheng, Hairong; El-Deiry, Wafik S.

2013-01-01

Introduction Cancer stem cells are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance, and therapeutic resistance. Restoring wild-type p53 function is an attractive new therapeutic approach for the treatment of cancer due to the well-described powerful tumor suppressor function of p53. As emerging evidence intimately links p53 and stem cell biology, this approach also provides an opportunity to target cancer stem cells. Areas covered Therapeutic approaches to restore the function of wild-type p53, cancer and normal stem cell biology in relation to p53, and the downstream effects of p53 on cancer stem cells. Expert opinion The restoration of wild-type p53 function by targeting p53 directly, its interacting proteins, or its family members holds promise as a new class of cancer therapies. This review examines the impact that such therapies may have on normal and cancer stem cells based on the current evidence linking p53 signaling with these populations. PMID:22998602

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

PubMed Central

Gross, Christina; Berry-Kravis, Elizabeth M; Bassell, Gary J

2012-01-01

Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. PMID:21796106

Endothelin therapeutics in cancer: Where are we?

PubMed

Rosanò, Laura; Bagnato, Anna

2016-03-15

In human cancers, the autocrine and paracrine loop mediated by the aberrantly activation of endothelin-1 (ET-1) receptor (ET-1R) elicits pleiotropic effects, preferentially mediated by the scaffold protein β-arrestin 1 (β-arr1), on tumor cells and on the host microenvironment, providing a strong rationale for targeting ET-1 receptors. This review describes the most up-to-date preclinical and clinical results obtained by using ET-1 therapeutics. The previous negative clinical results of ET-1 therapeutics should not prevent us from setting the standard of this class of drugs for future well-designed clinical trials. The preclinical data obtained with the dual ETAR and ETBR antagonist macitentan indicate that this molecule, which targets cancer cells and tumor-associated microenvironmental elements, could be a cancer therapeutic option. The field of ET-1 therapeutics will be improved in the next decade, facilitated by the new knowledge on the genomic landscape of the human stroma and tumor, and by the low invasive approaches based on liquid biopsies for the discovery of predictive biomarkers. The information obtained from preclinical studies in patient-derived models and from the Cancer Genome Atlas will set the scene of precision medicine for cancer. Results from these studies are expected to open the possibility that ET-1R antagonists might be more efficacious as molecular cancer therapeutics, able to hamper the functional β-arr1-dependent signaling complexes, either alone or coupled with new targeted approaches. Copyright © 2016 the American Physiological Society.

Therapeutic cloning: from consequences to contradiction.

PubMed

Coors, Marilyn

2002-06-01

The British Parliament legalized therapeutic cloning in December 2000 despite opposition from the European Union. The watershed event in Parliament's move was the active and unprecedented government support for the generation and destruction of human embryonic life merely as a means of medical advancement. This article contends that the utilitarian analysis of this procedure is necessary to identify the real world risks of therapeutic cloning but insufficient to identify the breach of defensible ethical limits that this procedure represents. A value-oriented approach to Kantian ethics demonstrates that the utilitarian endorsement of therapeutic cloning entails a contradiction of the necessity of human vulnerability and a faulty valuation of the human embryo. The concern is that a narrow utilitarian focus ultimately commodifies human embryonic life and preferences outcomes as the sole determinant of moral value.

Therapeutic Approaches Targeting MYC-Driven Prostate Cancer

PubMed Central

Rebello, Richard J.; Pearson, Richard B.; Hannan, Ross D.; Furic, Luc

2017-01-01

The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth. MYC activity also cooperates with the dysregulation of the phosphoinositol-3-kinase (PI3K)/AKT/mTOR pathway to promote PC cell survival. Recent advances in the understanding of these interactions through the use of animal models have provided significant insight into the therapeutic efficacy of targeting MYC activity by interfering with its transcriptional program, and indirectly by targeting downstream cellular events linked to MYC transformation potential. PMID:28212321

Therapy Talk: Analyzing Therapeutic Discourse

ERIC Educational Resources Information Center

Leahy, Margaret M.

2004-01-01

Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

Plant derived edible nanoparticles as a new therapeutic approach against diseases

PubMed Central

Zhang, Mingzhen; Viennois, Emilie; Xu, Changlong; Merlin, Didier

2016-01-01

ABSTRACT In plant cells, nanoparticles containing miRNA, bioactive lipids and proteins serve as extracellular messengers to mediate cell-cell communication in a manner similar to the exosomes secreted by mammalian cells. Notably, such nanoparticles are edible. Moreover, given the proper origin and cargo, plant derived edible nanoparticles could function in interspecies communication and may serve as natural therapeutics against a variety of diseases. In addition, nanoparticles made of plant-derived lipids may be used to efficiently deliver specific drugs. Plant derived edible nanoparticles could be more easily scaled up for mass production, compared to synthetic nanoparticles. In this review, we discuss recent significant developments pertaining to plant derived edible nanoparticles and provide insight into the use of plants as a bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles. PMID:27358751

Discovery and design of carbohydrate-based therapeutics.

PubMed

Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

2010-08-01

Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

Xeroderma pigmentosum: diagnostic procedures, interdisciplinary patient care, and novel therapeutic approaches.

PubMed

Lehmann, Janin; Schubert, Steffen; Emmert, Steffen

2014-10-01

Xeroderma pigmentosum (XP) is an autosomal recessive disease, caused by a gene defect in the nucleotide-excision-repair (NER) pathway or in translesional DNA synthesis. At the age of eight, patients already develop their first skin cancers due to this DNA repair defect. In contrast, in the Caucasian population the first tumor formation in UV exposed skin regions occurs at a mean age of 60. The clinical picture among patients suffering from XP is highly diverse and includes signs of accelerated skin aging, and UV-induced skin cancers, as well as ophthalmologic and neurological symptoms. Patients should therefore receive interdisciplinary care. This includes dermatologists, ophthalmologists, ENT specialists, neurologists, and human geneticists. Patients with XP are clinically diagnosed, but this may be supported by molecular-genetic and functional analyses. These analyses allow pinpointing the exact disease-causing gene defect (complementation group assignment, detection of the type and location of the mutation within the gene). The resulting information is already relevant to predict the course of disease and symptoms and probably will be utilized for individualized therapeutic approaches in the future. Recently, enhanced repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons by certain antibiotics could be demonstrated. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Targeting therapeutics to the glomerulus with nanoparticles.

PubMed

Zuckerman, Jonathan E; Davis, Mark E

2013-11-01

Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Clinically advancing and promising polymer-based therapeutics.

PubMed

Souery, Whitney N; Bishop, Corey J

2018-02-01

In this review article, we will examine the history of polymers and their evolution from provisional World War II materials to medical therapeutics. To provide a comprehensive look at the current state of polymer-based therapeutics, we will classify technologies according to targeted areas of interest, including central nervous system-based and intraocular-, gastrointestinal-, cardiovascular-, dermal-, reproductive-, skeletal-, and neoplastic-based systems. Within each of these areas, we will consider several examples of novel, clinically available polymer-based therapeutics; in addition, this review will also include a discussion of developing therapies, ranging from the in vivo to clinical trial stage, for each targeted area of treatment. Finally, we will emphasize areas of patient care in need of more effective, accessible, and targeted treatment approaches where polymer-based therapeutics may offer potential solutions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept.

PubMed

Peyrode, Caroline; Weber, Valérie; Voissière, Aurélien; Maisonial-Besset, Aurélie; Vidal, Aurélien; Auzeloux, Philippe; Gaumet, Vincent; Borel, Michèle; Dauplat, Marie-Mélanie; Quintana, Mercedes; Degoul, Françoise; Rédini, Françoise; Chezal, Jean-Michel; Miot-Noirault, Elisabeth

2016-11-01

To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosarcoma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [ 3 H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99m Tc-NTP 15-5 scintigraphic imaging of PGs, 1 H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the tolerability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma. Mol Cancer Ther; 15(11); 2575-85. ©2016 AACR. ©2016 American Association for Cancer Research.

Social Workers' Reflections on the Therapeutic Encounter With Elder Abuse and Neglect.

PubMed

Goldblatt, Hadass; Band-Winterstein, Tova; Alon, Sara

2016-02-24

The aim of this qualitative study was to explore social workers' reflections on their experience of the therapeutic encounter with victims and perpetrators of elder abuse and neglect. The research questions were as follows: How do social workers tune themselves toward the therapeutic encounter with elder abuse? How do they position themselves vis-à-vis the clients? How do social workers describe the meaning of the intervention both for the clients and for themselves? What is the added value of the therapeutic encounter in this field for the social workers? Participants were 17 experienced women social workers, who worked with abusers and with abused and neglected older adults in Israel. Data were collected via in-depth semi-structured interviews, which were later transcribed and content analyzed. Two main themes emerged from the findings, emphasizing two key aspects of the social workers' reflective process experienced during the therapeutic encounter: (a) focus on the client: "This is the journey of their lives"-reflection on the therapeutic "journey"; (b) focus on the social worker's inner and professional world: "'There is nothing to be done' is no longer in my vocabulary"-a personal and professional maturation process. The social workers expressed a positive attitude toward their elder clients. A unique dialogue developed in the therapeutic encounter, whereby the social workers considered any change as valuable if it allowed the elders a sense of control and self-worth, whereas the social workers were enriched by the elders' life experience, and matured both personally and professionally. Thus, both sides benefited from this reciprocal relationship. Implications for further research and practice are discussed. © The Author(s) 2016.

Levulinic acid: a valuable platform chemical for fermentative syntheses

USDA-ARS?s Scientific Manuscript database

In 2004 the DOE included levulinic acid (LA) as a top platform molecule because of its production from renewable resources in large yields and its broad application potential as a precursor for many valuable chemical derivatives. While LA and its chemical derivatives have high application potential,...

Neuropeptide Y, resilience, and PTSD therapeutics.

PubMed

Kautz, Marin; Charney, Dennis S; Murrough, James W

2017-05-10

Resilience to traumatic stress is a complex psychobiological process that protects individuals from developing posttraumatic stress disorder (PTSD) or other untoward consequences of exposure to extreme stress, including depression. Progress in translational research points toward the neuropeptide Y (NPY) system - among others - as a key mediator of stress response and as a potential therapeutic focus for PTSD. Substantial preclinical evidence supports the role of NPY in the modulation of stress response and in the regulation of anxiety in animal models. Clinical studies testing the safety and efficacy of modulating the NPY system in humans, however, have lagged behind. In the current article, we review the evidence base for targeting the NPY system as a therapeutic approach in PTSD, and consider impediments and potential solutions to therapeutic development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer

DTIC Science & Technology

2015-09-01

of metastatic disease when they are first diagnosed, yet many patients later return to the clinic with cancer that has spread throughout the body. It...treated before they experience disease relapse. 15. SUBJECT TERMS Breast cancer, metastasis, dissemination, recurrence, therapeutic resistance, systemic...instigation, microenvironment, bone marrow cells, canine , mouse models 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

IMPACT web portal: oncology database integrating molecular profiles with actionable therapeutics.

PubMed

Hintzsche, Jennifer D; Yoo, Minjae; Kim, Jihye; Amato, Carol M; Robinson, William A; Tan, Aik Choon

2018-04-20

With the advancement of next generation sequencing technology, researchers are now able to identify important variants and structural changes in DNA and RNA in cancer patient samples. With this information, we can now correlate specific variants and/or structural changes with actionable therapeutics known to inhibit these variants. We introduce the creation of the IMPACT Web Portal, a new online resource that connects molecular profiles of tumors to approved drugs, investigational therapeutics and pharmacogenetics associated drugs. IMPACT Web Portal contains a total of 776 drugs connected to 1326 target genes and 435 target variants, fusion, and copy number alterations. The online IMPACT Web Portal allows users to search for various genetic alterations and connects them to three levels of actionable therapeutics. The results are categorized into 3 levels: Level 1 contains approved drugs separated into two groups; Level 1A contains approved drugs with variant specific information while Level 1B contains approved drugs with gene level information. Level 2 contains drugs currently in oncology clinical trials. Level 3 provides pharmacogenetic associations between approved drugs and genes. IMPACT Web Portal allows for sequencing data to be linked to actionable therapeutics for translational and drug repurposing research. The IMPACT Web Portal online resource allows users to query genes and variants to approved and investigational drugs. We envision that this resource will be a valuable database for personalized medicine and drug repurposing. IMPACT Web Portal is freely available for non-commercial use at http://tanlab.ucdenver.edu/IMPACT .

The therapeutic impact of new migraine discoveries.

PubMed

Vécsei, Laszlo; Lukács, Melinda; Tajti, Janos; Fülöp, Ferenc; Toldi, Jozsef; Edvinsson, Lars

2018-05-29

Migraine is one the most disabling neurological conditions and associates with high socio-economic costs. Though certain aspects of the pathomechanism of migraine are still incompletely understood, the leading hypothesis implicates the role of the activation of the trigeminovascular system. Triptans are considered the current gold standard therapy for migraine attacks; however, their use in clinical practice is limited. Prophylactic treatment includes non-specific approaches for migraine prevention. All these support the need for future studies in order to develop innovative anti-migraine drugs. The present study is a review of the current literature regarding new therapeutic lines in migraine research. A systematic literature search in the database of PUBMED was conducted concerning therapeutic strategies in migraine published until July 2017. Ongoing clinical trials with 5-HT1F receptor agonists and glutamate receptor antagonists offer promising new aspects for acute migraine treatment. Monoclonal antibodies against CGRP and the CGRP receptor are revolutionary in preventive treatment; however, further long-term studies are needed to test their tolerability. Preclinical studies show positive results with PACAP- and kynurenic acid-related treatments. Other promising therapeutic strategies (such as those targeting TRPV1, substance P, NOS, or orexin) have failed to show efficacy in clinical trials. Due to their side-effects, current therapeutic approaches are not suitable for all migraine patients. Especially frequent episodic and chronic migraine represents a therapeutic challenge for researchers. Clinical and preclinical studies are needed to untangle the pathophysiology of migraine in order to develop new and migraine-specific therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Theranostics Using Antibodies and Antibody-Related Therapeutics.

PubMed

Moek, Kirsten L; Giesen, Danique; Kok, Iris C; de Groot, Derk Jan A; Jalving, Mathilde; Fehrmann, Rudolf S N; Lub-de Hooge, Marjolijn N; Brouwers, Adrienne H; de Vries, Elisabeth G E

2017-09-01

In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these drugs in oncology are particularly interesting because antibodies are designed against specific targets on the tumor cell membrane and immune cells as well as targets in the tumor microenvironment. In addition, these drugs are relatively easy to radiolabel. Noninvasive molecular imaging techniques, such as SPECT and PET, provide information on the whole-body distribution of radiolabeled mAbs and antibody-related therapeutics. Molecular antibody imaging can potentially elucidate drug target expression, tracer uptake in the tumor, tumor saturation, and heterogeneity for these parameters within the tumor. These data can support drug development and may aid in patient stratification and monitoring of the treatment response. Selecting a radionuclide for theranostic purposes generally starts by matching the serum half-life of the mAb or antibody-related therapeutic and the physical half-life of the radionuclide. Furthermore, PET imaging allows better quantification than the SPECT technique. This information has increased interest in theranostics using PET radionuclides with a relatively long physical half-life, such as 89 Zr. In this review, we provide an overview of ongoing research on mAbs and antibody-related theranostics in preclinical and clinical oncologic settings. We identified 24 antibodies or antibody-related therapeutics labeled with PET radionuclides for theranostic purposes in patients. For this approach to become integrated in standard care, further standardization with respect to the procedures involved is required. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

An antidote approach to reduce risk and broaden utility of antibody-based therapeutics.

PubMed

Portnoff, Alyse D; Gao, Cuihua; Borrok, M Jack; Gao, Xizhe; Gao, Changshou; Rainey, G Jonah

2017-05-19

Antibody therapeutics offer effective treatment options for a broad range of diseases. One of the greatest benefits of antibody therapeutics is their extraordinarily long serum half-life, allowing infrequent dosing with long-lasting effects. A characteristic of antibodies that drives long half-life is the ability to interact with the recycling receptor, FcRn, in a pH-dependent manner. The benefit of long half-life, however, carries with it liabilities. Although the positive effects of antibody therapeutics are long-lasting, any acute adverse events or chronic negative impacts, such as immunosuppression in the face of an infection, are also long-lasting. Therefore, we sought to develop antibodies with a chemical handle that alone would enjoy the long half-life of normal antibodies but, upon addition of a small-molecule antidote, would interact with the chemical handle and inhibit the antibody recycling mechanism, thus leading to rapid degradation and shortened half-life in vivo Here we present a proof of concept study where we identify sites to incorporate a non-natural amino acid that can be chemically modified to modulate FcRn interaction in vitro and antibody half-life in vivo This is an important first step in developing safer therapeutics, and the next step will be development of technology that can perform the modifying chemistry in vivo . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A metabolic network approach for the identification and prioritization of antimicrobial drug targets

PubMed Central

Chavali, Arvind K.; D’Auria, Kevin M.; Hewlett, Erik L.; Pearson, Richard D.; Papin, Jason A.

2012-01-01

For many infectious diseases, novel treatment options are needed to address problems with cost, toxicity and resistance to current drugs. Systems biology tools can be used to gain valuable insight into pathogenic processes and aid in expediting drug discovery. In the past decade, constraint-based modeling of genome-scale metabolic networks has become widely used. Focusing on pathogen metabolic networks, we review in silico strategies to identify effective drug targets, and we highlight recent successes as well as limitations associated with such computational analyses. We further discuss how accounting for the host environment and even targeting the host may offer new therapeutic options. These systems-level approaches are beginning to provide novel avenues for drug targeting against infectious agents. PMID:22300758

Engineering responsive supramolecular biomaterials: Toward smart therapeutics.

PubMed

Webber, Matthew J

2016-09-01

Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of "smart" materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment.

Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice.

PubMed

Tsuji, Takumi; Okuno, Satoshi; Kuroda, Ayano; Hamazaki, Junya; Chikami, Takuma; Sakurai, Sakura; Yoshida, Yuya; Banno, Rie; Fujita, Tetsuro; Kohno, Takeyuki

2016-04-01

The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model. Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical observations (epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression). Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups. FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Proteases as therapeutics

PubMed Central

Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

2015-01-01

Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

PubMed

Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

2016-01-19

The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

The potential of prison-based democratic therapeutic communities.

PubMed

Bennett, Jamie; Shuker, Richard

2017-03-13

Purpose The purpose of this paper is to describe the work of HMP Grendon, the only prison in the UK to operate entirely as a series of democratic therapeutic communities and to summarise the research of its effectiveness. Design/methodology/approach The paper is both descriptive, providing an overview of the work of a prison-based therapeutic community, and offers a literature review regarding evidence of effectiveness. Findings The work of HMP Grendon has a wide range of positive benefits including reduced levels of disruption in prison, reduced self-harm, improved well-being, an environment that is experienced as more humane and reduced levels of reoffending. Originality/value The work of HMP Grendon offers a well established and evidenced approach to managing men who have committed serious violent and sexually violent offences. It also promotes and embodies a progressive approach to managing prisons rooted in the welfare tradition.

Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.

PubMed

Zhou, Yinjian; Zhang, Chunling; Liang, Wei

2014-11-10

RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early. Copyright © 2014 Elsevier B.V. All rights reserved.

New technologies for application to veterinary therapeutics.

PubMed

Riviere, Jim E

2010-01-01

The purpose of this contribution is to review new technologies and make an educated prediction as to how they will impact veterinary pharmacology over the coming decades. By examining past developments, it becomes evident that change is incremental and predictable unless either a transforming discovery or a change in societal behaviour occurs. In the last century, both discoveries and behaviours have dramatically changed medicine, pharmacology and therapeutics. In this chapter, the potential effects of six transforming technologies on veterinary therapeutics are examined: continued advances in computer technology, microfluidics, nanotechnology, high-throughput screening, control and targeted drug delivery and pharmacogenomics. These should lead to the more efficacious and safer use of existing medicants, and the development of novel drugs across most therapeutic classes through increases in our knowledge base, as well as more efficient drug development. Although this growth in technology portends major advances over the next few decades, economic and regulatory constraints must still be overcome for these new drugs or therapeutic approaches to become common practise.

Molecular basis of human CD22 function and therapeutic targeting.

PubMed

Ereño-Orbea, June; Sicard, Taylor; Cui, Hong; Mazhab-Jafari, Mohammad T; Benlekbir, Samir; Guarné, Alba; Rubinstein, John L; Julien, Jean-Philippe

2017-10-02

CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals. We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement. Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.

43 CFR 2568.94 - Can I receive an allotment of land that is valuable for minerals?

Code of Federal Regulations, 2012 CFR

2012-10-01

... valuable for minerals? 2568.94 Section 2568.94 Public Lands: Interior Regulations Relating to Public Lands... be or believed to be valuable for coal, oil, or gas, but the ownership of these minerals remains with the Federal government. BLM cannot convey to you land valuable for other kinds of minerals such as...

43 CFR 2568.94 - Can I receive an allotment of land that is valuable for minerals?

Code of Federal Regulations, 2014 CFR

2014-10-01

... valuable for minerals? 2568.94 Section 2568.94 Public Lands: Interior Regulations Relating to Public Lands... be or believed to be valuable for coal, oil, or gas, but the ownership of these minerals remains with the Federal government. BLM cannot convey to you land valuable for other kinds of minerals such as...

43 CFR 2568.94 - Can I receive an allotment of land that is valuable for minerals?

Code of Federal Regulations, 2011 CFR

2011-10-01

... valuable for minerals? 2568.94 Section 2568.94 Public Lands: Interior Regulations Relating to Public Lands... be or believed to be valuable for coal, oil, or gas, but the ownership of these minerals remains with the Federal government. BLM cannot convey to you land valuable for other kinds of minerals such as...

Novel therapeutic approaches: Rett syndrome and human induced pluripotent stem cell technology

PubMed Central

Gomathi, Mohan

2017-01-01

Recent advances in induced pluripotent stem cell (iPSC) technology target screening and discovering of therapeutic agents for the possible cure of human diseases. Human induced pluripotent stem cells (hiPSC) are the right kind of platform for testing potency of specific active compounds. Ayurveda, the Indian traditional system of medicine developed between 2,500 and 500 BC, is a science involving the intelligent formulations of herbs and minerals. It can serve as a “goldmine” for novel neuroprotective agents used for centuries to treat neurological disorders. This review discusses limitations in screening drugs for neurological disorders and the advantages offered by hiPSC integrated with Indian traditional system of medicine. We begin by describing the current state of hiPSC technology in research on Rett syndrome (RTT) followed by the current controversies in RTT research combined with the emergence of patient-specific hiPSC that indicate an urgent need for researchers to understand the etiology and drug mechanism. We conclude by offering recommendations to reinforce the screening of active compounds present in the ayurvedic medicines using the human induced pluripotent neural model system for research involving drug discovery for RTT. This integrative approach will fill the current knowledge gap in the traditional medicines and drug discovery. PMID:28447035

Envisioning the future of polymer therapeutics for brain disorders.

PubMed

Rodriguez-Otormin, Fernanda; Duro-Castano, Aroa; Conejos-Sánchez, Inmaculada; Vicent, María J

2018-06-14

The growing incidence of brain-related pathologies and the problems that undermine the development of efficient and effective treatments have prompted both researchers and the pharmaceutical industry to search for novel therapeutic alternatives. Polymer therapeutics (PT) display properties well suited to the treatment of neuro-related disorders, which help to overcome the many hidden obstacles on the journey to the central nervous system (CNS). The inherent features of PT, derived from drug(s) conjugation, in parallel with the progress in synthesis and analytical methods, the increasing knowledge in molecular basis of diseases, and collected clinical data through the last four decades, have driven the translation from "bench to bedside" for various biomedical applications. However, since the approval of Gliadel® wafers, little progress has been made in the CNS field, even though brain targeting represents an ever-growing challenge. A thorough assessment of the steps required for successful brain delivery via different administration routes and the consideration of the disease-specific hallmarks are essential to progress in the field. Within this review, we hope to summarize the latest developments, successes, and failures and discuss considerations on designs and strategies for PT in the treatment of CNS disorders. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease. © 2018 Wiley Periodicals, Inc.

Targeting inflammation: new therapeutic approaches in chronic kidney disease (CKD).

PubMed

Impellizzeri, Daniela; Esposito, Emanuela; Attley, James; Cuzzocrea, Salvatore

2014-03-01

Chronic inflammation and oxidative stress, features that are closely associated with nuclear factor (NF-κB) activation, play a key role in the development and progression of chronic kidney disease (CKD). Several animal models and clinical trials have clearly demonstrated the effectiveness of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy to improve glomerular/tubulointerstitial damage, reduce proteinuria, and decrease CKD progression, but CKD treatment still represents a clinical challenge. Bardoxolone methyl, a first-in-class oral Nrf-2 (nuclear factor erythroid 2-related factor 2) agonist that until recently showed considerable potential for the management of a range of chronic diseases, had been shown to improve kidney function in patients with advanced diabetic nephropathy (DN) with few adverse events in a phase 2 trial, but a large phase 3 study in patients with diabetes and CKD was halted due to emerging toxicity and death in a number of patients. Instead, palmitoylethanolamide (PEA) a member of the fatty acid ethanolamine family, is a novel non-steroidal, kidney friendly anti-inflammatory and anti-fibrotic agent with a well-documented safety profile, that may represent a potential candidate in treating CKD probably by a combination of pharmacological properties, including some activity at the peroxisome proliferator activated receptor alpha (PPAR-α). The aim of this review is to discuss new therapeutic approaches for the treatment of CKD, with particular reference to the outcome of two therapies, bardoxolone methyl and PEA, to improve our understanding of which pharmacological properties are responsible for the anti-inflammatory effects necessary for the effective treatment of renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

A feminist approach for the treatment of drug-abusing women in a coed therapeutic community.

PubMed

Mandel, L; Schulman, J; Monteiro, R

1979-07-01

Experiences with female addicts in a feminist awareness group within a coed therapeutic community are reported. The group met for 16 months and was based on a variety of therapeutic techniques and educational presentations. The intervention resulted in more communication and trust among the women, increased interest in health-related concerns, a reduced sense of alienation, and gains in self-respect. The article discussed the issues and implications of resistance to the group, timing, development of indigenous leadership, training for feminist therapists, and the use of outside professional consultants in therapeutic communities.

RNA therapeutics targeting osteoclast-mediated excessive bone resorption

PubMed Central

Wang, Yuwei; Grainger, David W

2011-01-01

RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare crisis as average life expectancy increases worldwide. New therapeutics are needed for this increasing patient population. This review describes the diversity of molecular targets suitable for RNAi-based gene knock-down in osteoclasts to control osteoclast-mediated excessive bone resorption. We identify strategies for developing targeted siRNA delivery and efficient gene silencing, and describe opportunities and challenges of introducing siRNA as a therapeutic approach to hard and connective tissue disorders. PMID:21945356

43 CFR 2430.4 - Additional criteria for classification of lands valuable for public purposes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Additional criteria for classification of... (2000) DISPOSAL CLASSIFICATIONS Criteria for Disposal Classifications § 2430.4 Additional criteria for classification of lands valuable for public purposes. (a) To be valuable for public purposes, lands must be...

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

PubMed Central

Viola, Joana R.; Rafael, Diana F.; Wagner, Ernst; Besch, Robert; Ogris, Manfred

2013-01-01

Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed. PMID:23634303

Field Trips as Valuable Learning Experiences in Geography Courses

ERIC Educational Resources Information Center

Krakowka, Amy Richmond

2012-01-01

Field trips have been acknowledged as valuable learning experiences in geography. This article uses Kolb's (1984) experiential learning model to discuss how students learn and how field trips can help enhance learning. Using Kolb's experiential learning theory as a guide in the design of field trips helps ensure that field trips contribute to…

Conversational evidence in therapeutic dialogue.

PubMed

Strong, Tom; Busch, Robbie; Couture, Shari

2008-07-01

Family therapists' participation in therapeutic dialogue with clients is typically informed by evidence of how such dialogue is developing. In this article, we propose that conversational evidence, the kind that can be empirically analyzed using discourse analyses, be considered a contribution to widening psychotherapy's evidence base. After some preliminaries about what we mean by conversational evidence, we provide a genealogy of evaluative practice in psychotherapy, and examine qualitative evaluation methods for their theoretical compatibilities with social constructionist approaches to family therapy. We then move on to examine the notion of accomplishment in therapeutic dialogue given how such accomplishments can be evaluated using conversation analysis. We conclude by considering a number of research and pedagogical implications we associate with conversational evidence.

Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies.

PubMed

Cao, Lei; Fan, Lei; Xu, Wei; Li, Jian-Yong

2015-01-01

Mouse double minute 4 (MDM4) as a member of MDM family, is an oncogene emerging as an imperative negative regulator of p53. Tumor suppressor protein p53 plays a crucial role in cell cycle arrest, apoptosis and homeostasis. It has been reported that frequent inactivation of p53 was observed in numerous human cancers including hematologic malignancies. MDM4, the newly discovered modulator of p53 protein, is frequently amplified in various solid tumors such as cutaneous melanoma, retinoblastoma and hematological malignances such as chronic lymphocytic leukemia, acute myeloid leukemia and mantle cell lymphoma. Multiple evidences implicate that over-expression of MDM4 is associated with tumor progression and poor prognosis which can be reversed by knockdown of MDM4 expression or restoration of p53 function, and support the rationale for the design of future MDM4-specific therapeutics. This article discusses and focuses on using MDM4 as a novel biomarker as well as a therapeutic target for hematologic malignancies.

Progress and trends in complement therapeutics.

PubMed

Ricklin, Daniel; Lambris, John D

2013-01-01

The past few years have proven to be a highly successful and exciting period for the field of complement-directed drug discovery and development. Driven by promising experiences with the first marketed complement drugs, increased knowledge about the involvement of complement in health and disease, and improvements in structural and analytical techniques as well as animal models of disease, the field has seen a surge in creative approaches to therapeutically intervene at various stages of the cascade. An impressive panel of compounds that show promise in clinical trials is meanwhile being lined up in the pipelines of both small biotechnology and big pharmaceutical companies. Yet with this new focus on complement-targeted therapeutics, important questions concerning target selection, point and length of intervention, safety, and drug delivery emerge. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases and affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This chapter highlights the key changes in the field that shape our current perception of complement-targeted drugs and provides a brief overview of recent strategies and emerging trends. Selected examples of complement-related diseases and inhibitor classes are highlighted to illustrate the diversity and creativity in field.

Progress and Trends in Complement Therapeutics.

PubMed

Ricklin, Daniel; Lambris, John D

2013-01-01

The past few years have proven to be a highly successful and exciting period for the field of complement-directed drug discovery and development. Driven by promising experiences with the first marketed complement drugs, increased knowledge about the involvement of complement in health and disease, and improvements in structural and analytical techniques as well as animal models of disease, the field has seen a surge in creative approaches to therapeutically intervene at various stages of the cascade. An impressive panel of compounds that show promise in clinical trials is meanwhile being lined up in the pipelines of both small biotechnology and big pharmaceutical companies. Yet with this new focus on complement-targeted therapeutics, important questions concerning target selection, point and length of intervention, safety, and drug delivery emerge. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases and affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This chapter highlights the key changes in the field that shape our current perception of complement-targeted drugs and provides a brief overview of recent strategies and emerging trends. Selected examples of complement-related diseases and inhibitor classes are highlighted to illustrate the diversity and creativity in field.

Biopharmaceutics and Therapeutic Potential of Engineered Nanomaterials

PubMed Central

Liang, Xing-Jie; Chen, Chunying; Zhao, Yuliang; Jia, Lee; Wang, Paul C.

2009-01-01

Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are founding an important class of new materials with specific physicochemical properties different from bulk materials with the same compositions. The potential for nanomaterials is rapidly expanding with novel applications constantly being explored in different areas. The unique size-dependent properties of nanomaterials make them very attractive for pharmaceutical applications. Investigations of physical, chemical and biological properties of engineered nanomaterials have yielded valuable information. Cytotoxic effects of certain engineered nanomaterials towards malignant cells form the basis for one aspect of nanomedicine. It is inferred that size, three dimensional shape, hydrophobicity and electronic configurations make them an appealing subject in medicinal chemistry. Their unique structure coupled with immense scope for derivatization forms a base for exciting developments in therapeutics. This review article addresses the fate of absorption, distribution, metabolism and excretion (ADME) of engineered nanoparticles in vitro and in vivo. It updates the distinctive methodology used for studying the biopharmaceutics of nanoparticles. This review addresses the future potential and safety concerns and genotoxicity of nanoparticle formulations in general. It particularly emphasizes the effects of nanoparticles on metabolic enzymes as well as the parenteral or inhalation administration routes of nanoparticle formulations. This paper illustrates the potential of nanomedicine by discussing biopharmaceutics of fullerene derivatives and their suitability for diagnostic and therapeutic purposes. Future direction is discussed as well. PMID:18855608

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

PubMed Central

Sartor, R. Balfour; Wu, Gary D.

2017-01-01

Intestinal microbiota are involved in the pathogenesis of Crohn’s disease, ulcerative colitis, and pouchitis. We review the mechanisms by which these gut bacteria, fungi, and viruses mediate mucosal homeostasis, via their composite genes (metagenome) and metabolic products (metabolome). We explain how alterations to their profiles and functions under conditions of dysbiosis contribute to inflammation and effector immune responses that mediate inflammatory bowel diseases (IBD) in humans and enterocolitis in mice. It could be possible to engineer the intestinal environment by modifying the microbiota community structure or function to treat patients with IBD— either with individual agents, via dietary management, or as adjuncts to immunosuppressive drugs. We summarize the latest information on therapeutic use of fecal microbial transplantation and propose improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment. PMID:27769810

Osteitis pubis in elite athletes: Diagnostic and therapeutic approach

PubMed Central

Angoules, Antonios G

2015-01-01

Osteitis pubis (OP) is a debilitating overuse syndrome characterizing by pelvic pain and local tenderness over the pubic symphysis commonly encountered in athletes often involved in kicking, twisting and cutting activities in sports such as soccer and rugby and to a lesser degree distance running. It is a common source of groin pain in elite athletes attributable to pubis sympysis instability as the result of microtrauma caused by repetitive muscle strains on pubic bones. Diagnosis is based mainly on detailed sports history and a meticulous clinical examination, although occasionally is difficult to distinguish this nosological entity from other pathologies affecting the involved area which may occur concomitantly in the same patient. Radiologic examinations such as plain radiographs, magnetic resonance imaging and 3 phase bone isotope scanning may be helpful to differentiate from other clinical entities with similar clinical presentation. Most cases respond well to conservative treatment which includes several physical modalities and especially a progressive rehabilitation programmed individualized to each one of patients diagnosed with OP. Local injection therapies have been also been proposed as a non-operative therapeutic option for the efficient management of these patients. In refractory cases, surgical therapeutic strategies are warranted. These include several open or minimally invasive surgical interventions such as arthroscopic or open symphysis curettage, wedge or total resection of pubic sympysis, polypropylene mesh placement and pubic fusion. In this review a critical analysis of OP in elite athletes is performed with special focus on current concepts of diagnosis and management of this source of athletic groin pain. PMID:26495244

Does waist circumference uncorrelated with BMI add valuable information?

PubMed

Ngueta, Gerard; Laouan-Sidi, Elhadji A; Lucas, Michel

2014-09-01

Estimation of relative contribution of Body Mass Index (BMI) and waist circumference (WC) on health outcomes requires a regression model that includes both obesity metrics. But, multicollinearity could yield biased estimates. To address the multicollinearity issue between BMI and WC, we used the residual model approach. The standard WC (Y-axis) was regressed on the BMI (X-axis) to obtain residual WC. Data from two adult population surveys (Nunavik Inuit and James Bay Cree) were analysed to evaluate relative effect of BMI and WC on four cardiometabolic risk factors: insulin, triglycerides, systolic blood pressure and high-density lipoprotein levels. In multivariate models, standard WC and BMI were significantly associated with cardiometabolic outcomes. Residual WC was not linked with any outcomes. The BMI effect was weakened by including standard WC in the model, but its effect remained unchanged if residual WC was considered. The strong correlation between standard WC and BMI does not allow assessment of their relative contributions to health in the same model without a risk of making erroneous estimations. By contrast with BMI, fat distribution (residual WC) does not add valuable information to a model that already contains overall adiposity (BMI) in Inuit and Cree. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach.

PubMed

Cuadrado, Antonio; Manda, Gina; Hassan, Ahmed; Alcaraz, María José; Barbas, Coral; Daiber, Andreas; Ghezzi, Pietro; León, Rafael; López, Manuela G; Oliva, Baldo; Pajares, Marta; Rojo, Ana I; Robledinos-Antón, Natalia; Valverde, Angela M; Guney, Emre; Schmidt, Harald H H W

2018-04-01

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases. Copyright © 2018 by The Author(s).

Recent advances in (therapeutic protein) drug development

PubMed Central

Lagassé, H.A. Daniel; Alexaki, Aikaterini; Simhadri, Vijaya L.; Katagiri, Nobuko H.; Jankowski, Wojciech; Sauna, Zuben E.; Kimchi-Sarfaty, Chava

2017-01-01

Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016). PMID:28232867

Adolescent depression: clinical features and therapeutic strategies.

PubMed

Nardi, B; Francesconi, G; Catena-Dell'osso, M; Bellantuono, C

2013-06-01

Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

Vectorization of Nucleic Acids for Therapeutic Approach: Tutorial Review.

PubMed

Geinguenaud, Frederic; Guenin, Erwann; Lalatonne, Yoann; Motte, Laurence

2016-05-20

Oligonucleotides present a high therapeutic potential for a wide variety of diseases. However, their clinical development is limited by their degradation by nucleases and their poor blood circulation time. Depending on the administration mode and the cellular target, these macromolecules will have to cross the vascular endothelium, to diffuse through the extracellular matrix, to be transported through the cell membrane, and finally to reach the cytoplasm. To overcome these physiological barriers, many strategies have been developed. Here, we review different methods of DNA vectorization, discuss limitations and advantages of the various vectors, and provide new perspectives for future development.

Characterization and Recovery of Valuables from Waste Copper Smelting Slag

NASA Astrophysics Data System (ADS)

Prince, Sarfo; Young, Jamie; Ma, Guojun; Young, Courtney

Silicate slags produced from smelting copper concentrates contains valuables such as Cu and Fe as well as heavy metals such as Pb and As which are considered hazardous. In this paper, various slags were characterized with several techniques: SEM-MLA, XRD, TG-DTA and ICP-MS. A recovery process was developed to separate the valuables from the silicates thereby producing value-added products and simultaneously reducing environmental concerns. Results show that the major phases in air-cooled slag are fayalite and magnetite whereas the water-cooled slag is amorphous. Thermodynamic calculations and carbothermal reduction experiments indicate that most of Cu and Fe can be recovered from both types using minor amounts of lime and alumina and treating at 1350°C (1623K) or higher for 30 min. The secondary slag can be recycled to the glass and/or ceramic industries.

Prospects for nucleic acid-based therapeutics against hepatitis C virus.

PubMed

Lee, Chang Ho; Kim, Ji Hyun; Lee, Seong-Wook

2013-12-21

In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.

Ethical Perspectives on RNA Interference Therapeutics

PubMed Central

Ebbesen, Mette; Jensen, Thomas G.; Andersen, Svend; Pedersen, Finn Skou

2008-01-01

RNA interference is a mechanism for controlling normal gene expression which has recently begun to be employed as a potential therapeutic agent for a wide range of disorders, including cancer, infectious diseases and metabolic disorders. Clinical trials with RNA interference have begun. However, challenges such as off-target effects, toxicity and safe delivery methods have to be overcome before RNA interference can be considered as a conventional drug. So, if RNA interference is to be used therapeutically, we should perform a risk-benefit analysis. It is ethically relevant to perform a risk-benefit analysis since ethical obligations about not inflicting harm and promoting good are generally accepted. But the ethical issues in RNA interference therapeutics not only include a risk-benefit analysis, but also considerations about respecting the autonomy of the patient and considerations about justice with regard to the inclusion criteria for participation in clinical trials and health care allocation. RNA interference is considered a new and promising therapeutic approach, but the ethical issues of this method have not been greatly discussed, so this article analyses these issues using the bioethical theory of principles of the American bioethicists, Tom L. Beauchamp and James F. Childress. PMID:18612370

Introduction to Therapeutic Counseling. Third Edition.

ERIC Educational Resources Information Center

Kottler, Jeffrey A.; Brown, Robert W.

A personal need to create a student-centered introduction to therapeutic counseling gave rise to this text. Emphasized throughout the text is the belief that counselor education and training should be integrative and pragmatic. Chapters are organized into four main parts: (1) The Professional Counselor; (2) Counseling Antecedents and Approaches;…

Therapeutic writing and chronic pain: experiences of therapeutic writing in a cognitive behavioural programme for people with chronic pain.

PubMed

Furnes, Bodil; Dysvik, Elin

2012-12-01

To examine the experiences of therapeutic writing from the perspectives of patients attending a chronic pain management programme. Pain is a multifaceted experience. Increased awareness, understanding and gaining new insights are essential aspects of dealing with chronic pain. It is crucial to find powerful ways to cope with chronic pain. Several studies point to writing as a tool for managing such demanding life experiences. Therapeutic writing in a cognitive behavioural approach may be used to facilitate the rehabilitation process. A qualitative study with a descriptive and explorative design including a phenomenological perspective was used. A consecutive sample of 34 outpatients with chronic pain was recruited to an eight-week group-based pain management programme. A therapeutic writing tool was developed and included as part of the homework tasks. Guidelines were used to initiate and guide the therapeutic writing activity. Written reports were collected after completion. Three thematic findings emerged from the analysis: 'increased understanding of chronic pain as a multifaceted experience', 'new insights into managing the chronic pain situation' and 'different performances lead to different experiences with therapeutic writing'. Increased awareness, understanding and new insights are essential to dealing with chronic pain. People with chronic pain need tools and skills for optimal adaptation. Our findings suggest therapeutic writing may strengthen cognitive behavioural therapy by facilitating cognitive restructuring processes. Therapeutic writing may be used as a tool to express individual experiences and to improve adaptation to chronic pain. © 2012 Blackwell Publishing Ltd.

HISTORICAL ANALYSIS, A VALUABLE TOOL IN COMMUNITY-BASED ENVIRONMENTAL PROTECTION

EPA Science Inventory

A historical analysis of the ecological consequences of development can be a valuable tool in community-based environmental protection. These studies can engage the public in environmental issues and lead to informed decision making. Historical studies provide an understanding of...

Modes of therapeutic action.

PubMed

Jones, E E

1997-12-01

The dialectic in psychoanalysis between theories about the mutative effects of interpretation and psychological knowledge and those concerning the effects of interpersonal interaction constitutes an important tension for approaches to psychoanalytic technique. This essay briefly summarises the thinking around these alternative conceptualisations of therapeutic action, and introduces a new empirically derived model, that of 'repetitive interaction structure', which attempts to bridge therapeutic action by insight and by relationship. Interaction structure is a way of formulating those aspects of the analytic process that have come to be termed intersubjectivity, transference-countertransference enactments and role responsiveness. The concept operationalises important aspects of interpersonal interaction, and can help specify the two-person patterns that emerge in an analysis. Patient and analyst interact in repetitive ways; these patterns of interaction, which are slow to change, probably reflect the psychological structure of both patient and analyst, whether psychic structure is conceptualised in terms of object-representations or compromise formations and impulse-defence configurations. Therapeutic action is located in the experience, recognition and understanding by patient and analyst of these repetitive interactions. Interaction structures stress the importance of the intrapsychic as a basis for what becomes manifest in the interactive field. Clinical illustrations from a psychoanalysis are provided, and research on repetitive interaction structures is described.

Patients' experiences with technology during inpatient rehabilitation: opportunities to support independence and therapeutic engagement.

PubMed

Fager, Susan Koch; Burnfield, Judith M

2014-03-01

To understand individuals' perceptions of technology use during inpatient rehabilitation. A qualitative phenomenological study using semi-structured interviews of 10 individuals with diverse underlying diagnoses and/or a close family member who participated in inpatient rehabilitation. Core themes focused on assistive technology usage (equipment set-up, reliability and fragility of equipment, expertise required to use assistive technology and use of mainstream technologies) and opportunities for using technology to increase therapeutic engagement (opportunities for practice outside of therapy, goals for therapeutic exercises and technology for therapeutic exercises: motivation and social interaction). Interviews revealed the need for durable, reliable and intuitive technology without requiring a high level of expertise to install and implement. A strong desire for the continued use of mainstream devices (e.g. cell phones, tablet computers) reinforces the need for a wider range of access options for those with limited physical function. Finally, opportunities to engage in therapeutically meaningful activities beyond the traditional treatment hours were identified as valuable for patients to not only improve function but to also promote social interaction. Assistive technology increases functional independence of severely disabled individuals. End-users (patients and families) identified a need for designs that are durable, reliable, intuitive, easy to consistently install and use. Technology use (adaptive or commercially available) provides a mechanism to extend therapeutic practice beyond the traditional therapy day. Adapting skeletal tracking technology used in gaming software could automate exercise tracking, documentation and feedback for patient motivation and clinical treatment planning and interventions.

Nanotechnology—novel therapeutics for CNS disorders

PubMed Central

Srikanth, Maya; Kessler, John A.

2013-01-01

Research into treatments for diseases of the CNS has made impressive strides in the past few decades, but therapeutic options are limited for many patients with CNS disorders. Nanotechnology has emerged as an exciting and promising new means of treating neurological disease, with the potential to fundamentally change the way we approach CNS-targeted therapeutics. Molecules can be nanoengineered to cross the blood–brain barrier, target specific cell or signalling systems, respond to endogenous stimuli, or act as vehicles for gene delivery, or as a matrix to promote axon elongation and support cell survival. The wide variety of available nanotechnologies allows the selection of a nanoscale material with the characteristics best suited to the therapeutic challenges posed by an individual CNS disorder. In this Review, we describe recent advances in the development of nanotechnology for the treatment of neurological disorders—in particular, neurodegenerative disease and malignant brain tumours—and for the promotion of neuroregeneration. PMID:22526003

Drug-Free Macromolecular Therapeutics – A New Paradigm in Polymeric Nanomedicines

PubMed Central

Chu, Te-Wei; Kopeček, Jindřich

2015-01-01

This review highlights a unique research area in polymer-based nanomedicine designs. Drug-free macromolecular therapeutics induce apoptosis of malignant cells by the crosslinking of surface non-internalizing receptors. The receptor crosslinking is mediated by the biorecognition of high-fidelity natural binding motifs (such as antiparallel coiled-coil peptides or complementary oligonucleotides) that are grafted to the side chains of polymers or attached to targeting moieties against cell receptors. This approach features the absence of low-molecular-weight cytotoxic compounds. Here, we summarize the rationales, different designs, and advantages of drug-free macromolecular therapeutics. Recent developments of novel therapeutic systems for B-cell lymphomas are discussed, as well as relevant approaches for other diseases. We conclude by pointing out various potential future directions in this exciting new field. PMID:26191406

The intercultural and interracial therapeutic relationship: challenges and recommendations.

PubMed

Qureshi, Adil; Collazos, Francisco

2011-01-01

Although research has demonstrated that mental health services function with patients from different cultural backgrounds, a variety of culture- and race-related factors can result in services being of lower quality than that which occurs when the clinician and patient are from the same culture. The provision of culturally competent care requires many institutional and organizational adaptations that lie beyond the control of most mental health professionals. The therapeutic relationship, however, remains a key factor of mental healthcare that can be attended to by individual therapists. The therapeutic relationship plays an important role in almost every therapeutic approach, and has been increasingly recognized as representing a means to the provision of quality intercultural and interracial treatment. At the same time, a host of cultural and racial factors relating to both the patient and clinician can compromise the development of the therapeutic relationship. This paper will explore some of the key issues that complicate therapeutic contact and communication, and will outline means by which to strengthen key components of the therapeutic relationship.

Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

PubMed

Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

2016-09-01

Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging Therapeutic Approaches to Mitochondrial Diseases

ERIC Educational Resources Information Center

Wenz, Tina; Williams, Sion L.; Bacman, Sandra R.; Moraes, Carlos T.

2010-01-01

Mitochondrial diseases are very heterogeneous and can affect different tissues and organs. Moreover, they can be caused by genetic defects in either nuclear or mitochondrial DNA as well as by environmental factors. All of these factors have made the development of therapies difficult. In this review article, we will discuss emerging approaches to…

Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases.

PubMed

Spudich, James A

2014-03-18

With the advent of technologies to obtain the complete sequence of the human genome in a cost-effective manner, this decade and those to come will see an exponential increase in our understanding of the underlying genetics that lead to human disease. And where we have a deep understanding of the biochemical and biophysical basis of the machineries and pathways involved in those genetic changes, there are great hopes for the development of modern therapeutics that specifically target the actual machinery and pathways altered by individual mutations. Prime examples of such a genetic disease are those classes of hypertrophic and dilated cardiomyopathy that result from single amino-acid substitutions in one of several of the proteins that make up the cardiac sarcomere or from the truncation of myosin binding protein C. Hypertrophic cardiomyopathy alone affects ∼1 in 500 individuals, and it is the leading cause of sudden cardiac death in young adults. Here I describe approaches to understand the molecular basis of the alterations in power output that result from these mutations. Small molecules binding to the mutant sarcomeric protein complex should be able to mitigate the effects of hypertrophic and dilated cardiomyopathy mutations at their sources, leading to possible new therapeutic approaches for these genetic diseases. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Therapeutic Relationship Between Male Nursing Students and Female Patients.

PubMed

Chan, Zenobia C Y; Chan, Vera W S; Tse, Judy K M

2014-07-01

This article explores the therapeutic relationship between male nursing students and female patients, through the use of autobiography in a qualitative approach. For this study, 18 male nursing students enrolled in master's and bachelor's programs in Hong Kong were recruited. They were asked to make records in a diary and draw pictures of their therapeutic relationship with female patients from their clinical experiences and then participate in a focus group interview. Content analysis was carried out on the collected data. The essential factors influencing the development of a therapeutic relationship were found to be gender, symbolic meanings, and career features. Good experiences were also discussed. The results shed light on the experiences of male nursing students and how they make sense of their therapeutic relationship with female patients. © The Author(s) 2013.

New targets for neuropathic pain therapeutics.

PubMed

Kinloch, Ross A; Cox, Peter J

2005-08-01

Neuropathic pain (NeP) is initiated by a lesion or dysfunction in the nervous system. Unlike physiological pain it serves no useful purpose and is usually sustained and chronic. NeP encompasses a wide range of pain syndromes of diverse aetiologies which together account for > 12 million sufferers in the US. Currently, there are a number of therapies available for NeP, including gabapentin, pregabalin, anticonvulsants (tiagabine HCl), tricyclic antidepressants (amitriptyline, nortriptyline) and acetaminophen/opioid combination products (Vicodin, Tylenol #3). However, these products do not provide sufficient pain relief and a significant proportion of sufferers are refractory (60%). Therefore, there is a need for new therapies that provide more predictable efficacy in all patients with improved tolerability. Over the last decade, understanding of the basic mechanisms contributing to the generation of NeP in preclinical animal models has greatly improved. Together with the completion of the various genome sequencing projects and significant advances in microarray and target validation strategies, new therapeutic approaches are being rigourously pursued. This article reviews the rationale behind a number of these mechanism-based approaches, briefly discusses specific challenges that they face, and finally, speculates on the potential of emerging technologies as alternative therapeutic strategies to the traditional 'small-molecule' approach.

Development of anti-migraine therapeutics using the capsaicin-induced dermal blood flow model.

PubMed

Buntinx, Linde; Vermeersch, Steve; de Hoon, Jan

2015-11-01

The efficacy of calcitonin gene-related peptide (receptor) (CGRP-(R)) blocking therapeutics in the treatment of acute migraine headache provided proof-of-concept for the involvement of CGRP in the pathophysiology of this disorder. One of the major hurdles for the development of any class of drugs, including CGRP blocking therapeutics, is the early clinical development process during which toxic and inefficacious compounds need to be eliminated as early as possible in order to focus on the most promising molecules. At this stage, human models providing proof of target engagement, combined with safety and tolerability studies, are extremely valuable in focusing on those therapeutics that have the highest engagement from the lowest exposure. They guide the go/no-go decision making, establish confidence in the candidate molecule by de-risking toxicity and safety issues and thereby speed up the early clinical development. In this review the focus is on the so called 'capsaicin model' as a typical example of a target engagement biomarker used as a human model for the development of CGRP blocking therapeutics. By applying capsaicin onto the skin, TRPV1 channels are activated and a CGRP-mediated increase in dermal blood flow can be quantified with laser Doppler perfusion imaging. Effective CGRP blocking therapeutics in turn, display blockade of this response. The translation of this biomarker model from animals to humans is discussed as well as the limitations of the assay in predicting the efficacy of anti-migraine drugs. © 2015 The British Pharmacological Society.

Stem cells: The Next Therapeutic Frontier

PubMed Central

Humes, H. David

2005-01-01

Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine, and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders. Blood transfusions and bone marrow transplantation are prime examples of the successful application of cell-based therapeutics; but recent advances in cellular and molecular biology have expanded the potential applications of this approach. Although recombinant genetic engineering to produce a variety of therapeutics such as human erythropoietin and insulin has proven successful, these treatments are unable to completely correct or reverse disease states, because most common disease processes are not due to the deficiency of a single protein but develop due to alterations in the complex interactions of a variety of cell components. In these complex situations, cell-based therapy may be a more successful strategy by providing a dynamic, interactive, and individualized therapeutic approach that responds to the pathophysiological condition of the patient. In this regard, cells may provide innovative methods for drug delivery of biologics, immunotherapy, and tissue regenerative or replacement engineering (1,2). The translation of this discipline to medical practice has tremendous potential, but in many applications technological issues need to be overcome. Since many cell-based indications are already being evaluated in the clinic, the field appears to be on the threshold of a number of successes. This review will focus on our group's use of human stem/progenitor cells in the treatment of acute and chronic renal failure as extensions to the current successful renal substitution processes of hemodialysis and hemofiltration. PMID:16555613

Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

PubMed

Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

2015-01-01

This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

LncRNA-DANCR: A valuable cancer related long non-coding RNA for human cancers.

PubMed

Thin, Khaing Zar; Liu, Xuefang; Feng, Xiaobo; Raveendran, Sudheesh; Tu, Jian Cheng

2018-06-01

Long noncoding RNAs (lncRNA) are a type of noncoding RNA that comprise of longer than 200 nucleotides sequences. They can regulate chromosome structure, gene expression and play an essential role in the pathophysiology of human diseases, especially in tumorigenesis and progression. Nowadays, they are being targeted as potential biomarkers for various cancer types. And many research studies have proven that lncRNAs might bring a new era to cancer diagnosis and support treatment management. The purpose of this review was to inspect the molecular mechanism and clinical significance of long non-coding RNA- differentiation antagonizing nonprotein coding RNA(DANCR) in various types of human cancers. In this review, we summarize and figure out recent research studies concerning the expression and biological mechanisms of lncRNA-DANCR in tumour development. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library. Long non-coding RNAs-DANCR is a valuable cancer-related lncRNA that its dysregulated expression was found in a variety of malignancies, including hepatocellular carcinoma, breast cancer, glioma, colorectal cancer, gastric cancer, and lung cancer. The aberrant expressions of DANCR have been shown to contribute to proliferation, migration and invasion of cancer cells. Long non-coding RNAs-DANCR likely serves as a useful disease biomarker or therapeutic cancer target. Copyright © 2018 Elsevier GmbH. All rights reserved.

A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation.

PubMed

Kleikers, Pamela W M; Hooijmans, Carlijn; Göb, Eva; Langhauser, Friederike; Rewell, Sarah S J; Radermacher, Kim; Ritskes-Hoitinga, Merel; Howells, David W; Kleinschnitz, Christoph; Schmidt, Harald H H W

2015-08-27

Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.

The 'world of yoga': the production and reproduction of therapeutic landscapes.

PubMed

Hoyez, Anne-Cécile

2007-07-01

Yoga is becoming more and more fashionable all around the world. This activity, partly considered as therapeutic, reveals contemporary ways of producing global practices. Via a questionnaire completed by individuals at yoga centres in India and France, the paper analyses this phenomenon using the concept of therapeutic landscapes. Furthermore, it examines how these therapeutic landscapes are influenced by globalisation. Bringing together the concepts of therapeutic landscapes, globalisation and the practice of yoga, the paper analyses the production and reproduction of yogic therapeutic landscapes in the world's space. Constituted of natural physical elements and built structures, these therapeutic landscapes are also strongly linked to emotional qualities and intimate feelings evoked by the place and related to health and well-being. The paper also underlines that the emergence of internationally recognised therapeutic landscapes demands a cultural and social geographical approach that could help to examine the repercussions of local and global phenomena on therapeutic landscapes. Indeed, very often, yogis, all around the world, refer to ideal places where they rarely go. Consequently, they create an imagined therapeutic environment that the paper describes.

Analysis of the proteolysis of bioactive peptides using a peptidomics approach

PubMed Central

Kim, Yun-Gon; Lone, Anna Mari; Saghatelian, Alan

2014-01-01

Identifying the peptidases that inactivate bioactive peptides (e.g. peptide hormones and neuropeptides) in mammals is an important unmet challenge. This protocol describes a recent approach that combines liquid chromatography-mass spectrometry peptidomics to identify endogenous cleavage sites of a bioactive peptide, the subsequent biochemical purification of a candidate peptidase based on these cleavage sites, and validation of the candidate peptidase’s role in the physiological regulation of the bioactive peptide by examining a peptidase knockout mouse. We highlight successful application of this protocol to discover that insulin-degrading enzyme (IDE) regulates physiological calcitonin gene-related peptide (CGRP) levels and detail the key stages and steps in this approach. This protocol requires 7 days of work; however, the total time for this protocol is highly variable because of its dependence on the availability of biological reagents, namely purified enzymes and knockout mice. The protocol is valuable because it expedites the characterization of mammalian peptidases, such as IDE, which in certain instances can be used to develop novel therapeutics. PMID:23949379

A review on phytochemistry and therapeutic uses of Hibiscus sabdariffa L.

PubMed

Riaz, Ghazala; Chopra, Rajni

2018-06-01

Hibiscus sabdariffa L. (roselle) belonging to the Malvaceae family is widely grown in many countries. This plant is often used in the traditional medicine being rich in phytochemicals like polyphenols especially anthocyanins, polysaccharides and organic acids thus having enormous prospective in modern therapeutic uses. The study aimed to review and document all the available evidence and information about the calyces of Hibiscus sabdariffa (roselle) with the special focus on their nutritional composition, bioactive constituents and therapeutic uses. The electronic database was searched up to 2017, using keywords Hibiscus sabdariffa, chemical constituents of roselle, therapeutic uses of roselle. Journals, books and conference proceedings were also searched. The review provides valuable information about the nutraceutical component of Hibiscus sabdariffa L. and their utilization for curing various degenerative diseases like hypertension, hyperlipidemia, cancer and other inflammatory diseases of liver and kidney. Their toxicological effects have also been discussed from a safety point of view. Most studies supported and provided the scientific basis for the statement that Hibiscus sabdariffa and their active constituents play an important role in the prevention of chronic and degenerative diseases that are associated with oxidative stress. Our study suggests, that good research is needed, to establish a potential strategy that can balance the pharmacological and toxic effects of roselle and standardized fingerprint of Hibiscus sabdariffa is required internationally for quality control. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications

PubMed Central

Macciò, Antonio; Madeddu, Clelia

2011-01-01

Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Although early diagnosis has contributed to therapeutic success, breast cancer remains a major health issue. In the last few year the hormone therapy for estrogen-dependent breast cancer has evolved achieving significant clinical results; at the same time, it has enabled us to better define the role of estrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. Specific obesity-associated factors, including leptin, insulin and inflammatory mediators, seem to influence breast cancer growth and prognosis independently of estrogens and at least in part by interacting with estrogen signalling at a cellular level. Therefore, a careful assessment of the nutritional status and body composition is paramount for a proper therapeutic approach for postmenopausal breast carcinoma. The use of antidiabetic and anti-inflammatory drugs associated with conventional hormone therapies and dietary/physical interventions could offer a new therapeutic approach for breast carcinoma that develops in the context of adiposity. PMID:22125453

Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy

PubMed Central

Clossen, Bryan L.; Reddy, Doodipala Samba

2017-01-01

This article describes the recent advances in epileptogenesis and novel therapeutic approaches for the prevention of epilepsy, with a special emphasis on the pharmacological basis of disease-modification of epileptogenesis for curing epilepsy. Here we assess animal studies and human clinical trials of epilepsy spanning 1982–2016. Epilepsy arises from a number of neuronal factors that trigger epileptogenesis, which is the process by which a brain shifts from a normal physiologic state to an epileptic condition. The events precipitating these changes can be of diverse origin, including traumatic brain injury, cerebrovascular damage, infections, chemical neurotoxicity, and emergency seizure conditions such as status epilepticus. Expectedly, the molecular and system mechanisms responsible for epileptogenesis are not well defined or understood. To date, there is no approved therapy for the prevention of epilepsy. Epigenetic dysregulation, neuroinflammation, and neurodegeneration appear to trigger epileptogenesis. Targeted drugs are being identified that can truly prevent the development of epilepsy in at-risk people. The promising agents include rapamycin, COX-2 inhibitors, TRK inhibitors, epigenetic modulators, JAK-STAT inhibitors, and neurosteroids. Recent evidence suggests that neurosteroids may play a role in modulating epileptogenesis. A number of promising drugs are under investigation for the prevention or modification of epileptogenesis to halt the development of epilepsy. Some drugs in development appear rational for preventing epilepsy because they target the initial trigger or related signaling pathways as the brain becomes progressively more prone to seizures. Additional research into the target validity and clinical investigation is essential to make new frontiers in curing epilepsy. PMID:28179120

Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.

PubMed

Clossen, Bryan L; Reddy, Doodipala Samba

2017-06-01

This article describes the recent advances in epileptogenesis and novel therapeutic approaches for the prevention of epilepsy, with a special emphasis on the pharmacological basis of disease-modification of epileptogenesis for curing epilepsy. Here we assess animal studies and human clinical trials of epilepsy spanning 1982-2016. Epilepsy arises from a number of neuronal factors that trigger epileptogenesis, which is the process by which a brain shifts from a normal physiologic state to an epileptic condition. The events precipitating these changes can be of diverse origin, including traumatic brain injury, cerebrovascular damage, infections, chemical neurotoxicity, and emergency seizure conditions such as status epilepticus. Expectedly, the molecular and system mechanisms responsible for epileptogenesis are not well defined or understood. To date, there is no approved therapy for the prevention of epilepsy. Epigenetic dysregulation, neuroinflammation, and neurodegeneration appear to trigger epileptogenesis. Targeted drugs are being identified that can truly prevent the development of epilepsy in at-risk people. The promising agents include rapamycin, COX-2 inhibitors, TRK inhibitors, epigenetic modulators, JAK-STAT inhibitors, and neurosteroids. Recent evidence suggests that neurosteroids may play a role in modulating epileptogenesis. A number of promising drugs are under investigation for the prevention or modification of epileptogenesis to halt the development of epilepsy. Some drugs in development appear rational for preventing epilepsy because they target the initial trigger or related signaling pathways as the brain becomes progressively more prone to seizures. Additional research into the target validity and clinical investigation is essential to make new frontiers in curing epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

Therapeutic micro-environments in the Edgelands: A thematic analysis of Richard Mabey's The Unofficial Countryside.

PubMed

Houghton, Frank; Houghton, Sharon

2015-05-01

The concept of therapeutic landscapes, as introduced by Gesler, has had a significant impact on what has become a reformed geography (or geographies) of health. Research in this field has developed the number and type of sites that have been characterised as therapeutic landscapes. A wide range of environments have now been explored through the analytical lens of the 'therapeutic landscape'. This research further expands current descriptions of such environments by exploring Edgelands as therapeutic micro landscapes. Edgelands refer to the neglected and routinely ignored interfacial zone between urban and rural that are a routine characteristic of the urban fringe resulting from dynamic cycles of urban development and decay. Using a hybrid method of thematic analysis incorporating both inductive and deductive approaches, this research explores Richard Mabey's seminal work on this topic, The Unofficial Countryside. Previous examinations of the features of therapeutic environments are therefore scrutinised to explore both scale and the possibility of further extending the kind of environments that may be described as therapeutic to include Edgelands. This approach is informed, in part, by principles of mindfulness, a historically Eastern, but increasingly Western approach to exploring oneself and the environment. This research identifies that these overlooked and neglected landscapes are in fact vibrant, resilient and enthralling environments teeming with life, renewal and re-birth. Examination reveals that there are three crucial outcomes of this research. The first relates to the issue of scale. Mabey's book provides evidence of the importance of micro environments in providing a therapeutic environmental focus. Secondly, this research explores the potential of mindfulness as an approach in Geography. Lastly, this research also identifies Edgelands as therapeutic sites and calls for an increased understanding and appreciation of their potential. Copyright © 2014

Effect of therapeutic interchange on medication reconciliation during hospitalization and upon discharge in a geriatric population

PubMed Central

Wang, Jessica S.; Fogerty, Robert L.

2017-01-01

Background Therapeutic interchange of a same class medication for an outpatient medication is a widespread practice during hospitalization in response to limited hospital formularies. However, therapeutic interchange may increase risk of medication errors. The objective was to characterize the prevalence and safety of therapeutic interchange. Methods and findings Secondary analysis of a transitions of care study. We included patients over age 64 admitted to a tertiary care hospital between 2009–2010 with heart failure, pneumonia, or acute coronary syndrome who were taking a medication in any of six commonly-interchanged classes on admission: proton pump inhibitors (PPIs), histamine H2-receptor antagonists (H2 blockers), hydroxymethylglutaryl CoA reductase inhibitors (statins), angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and inhaled corticosteroids (ICS). There was limited electronic medication reconciliation support available. Main measures were presence and accuracy of therapeutic interchange during hospitalization, and rate of medication reconciliation errors on discharge. We examined charts of 303 patients taking 555 medications at time of admission in the six medication classes of interest. A total of 244 (44.0%) of medications were therapeutically interchanged to an approved formulary drug at admission, affecting 64% of the study patients. Among the therapeutically interchanged drugs, we identified 78 (32.0%) suspected medication conversion errors. The discharge medication reconciliation error rate was 11.5% among the 244 therapeutically interchanged medications, compared with 4.2% among the 311 unchanged medications (relative risk [RR] 2.75, 95% confidence interval [CI] 1.45–5.19). Conclusions Therapeutic interchange was prevalent among hospitalized patients in this study and elevates the risk for potential medication errors during and after hospitalization. Improved electronic systems for managing therapeutic

A systematic approach to identify therapeutic effects of natural products based on human metabolite information.

PubMed

Noh, Kyungrin; Yoo, Sunyong; Lee, Doheon

2018-06-13

Natural products have been widely investigated in the drug development field. Their traditional use cases as medicinal agents and their resemblance of our endogenous compounds show the possibility of new drug development. Many researchers have focused on identifying therapeutic effects of natural products, yet the resemblance of natural products and human metabolites has been rarely touched. We propose a novel method which predicts therapeutic effects of natural products based on their similarity with human metabolites. In this study, we compare the structure, target and phenotype similarities between natural products and human metabolites to capture molecular and phenotypic properties of both compounds. With the generated similarity features, we train support vector machine model to identify similar natural product and human metabolite pairs. The known functions of human metabolites are then mapped to the paired natural products to predict their therapeutic effects. With our selected three feature sets, structure, target and phenotype similarities, our trained model successfully paired similar natural products and human metabolites. When applied to the natural product derived drugs, we could successfully identify their indications with high specificity and sensitivity. We further validated the found therapeutic effects of natural products with the literature evidence. These results suggest that our model can match natural products to similar human metabolites and provide possible therapeutic effects of natural products. By utilizing the similar human metabolite information, we expect to find new indications of natural products which could not be covered by previous in silico methods.

Introduction to metabolic genetic engineering for the production of valuable secondary metabolites in in vivo and in vitro plant systems.

PubMed

Benedito, Vagner A; Modolo, Luzia V

2014-01-01

Plants are capable of producing a myriad of chemical compounds. While these compounds serve specific functions in the plant, many have surprising effects on the human body, often with positive action against diseases. These compounds are often difficult to synthesize ex vivo and require the coordinated and compartmentalized action of enzymes in living organisms. However, the amounts produced in whole plants are often small and restricted to single tissues of the plant or even cellular organelles, making their extraction an expensive process. Since most natural products used in therapeutics are specialized, secondary plant metabolites, we provide here an overview of the classification of the main classes of these compounds, with its biochemical pathways and how this information can be used to create efficient in and ex planta production pipelines to generate highly valuable compounds. Metabolic genetic engineering is introduced in light of physiological and genetic methods to enhance production of high-value plant secondary metabolites.

A novel approach to make homogeneous protease-stable monovalent streptavidin

DOE PAGES

Zhang, M.; Shao, J; Xiao, J.; ...

2015-06-11

The interaction between the tetramer streptavidin and biotin is recognized as one of the strongest non-covalent associations. Owing to the tight and specific binding, the streptavidin-biotin system has been used widely for bimolecular labeling, purification, immobilization, and even for targeted delivery of therapeutics drugs. Here, we report a novel approach to make homogeneous monovalent tetramer streptavidin. The purified monovalent protein showed both thermal stability and protease stability. Unexpectedly, we found that two proteases, Proteinase K (PK) and Subtilisin (SU), can efficiently remove the His8-tag from the wild-type subunit without affecting the tetramer architecture of monovalent streptavidin, thus making it moremore » homogeneous. In addition, crystallization was performed to assure the homogeneity of the monovalent protein prepared. Overall, monovalent streptavidin shows increased homogeneity and will likely be valuable for many future applications in a wide range of research areas.« less

Improving Lithium Therapeutics by Crystal Engineering of Novel Ionic Cocrystals

PubMed Central

2013-01-01

Current United States Food and Drug Administration (FDA)-approved lithium salts are plagued with a narrow therapeutic window. Recent attempts to find alternative drugs have identified new chemical entities, but lithium’s polypharmacological mechanisms for treating neuropsychiatric disorders are highly debated and are not yet matched. Thus, re-engineering current lithium solid forms in order to optimize performance represents a low cost and low risk approach to the desired therapeutic outcome. In this contribution, we employed a crystal engineering strategy to synthesize the first ionic cocrystals (ICCs) of lithium salts with organic anions. We are unaware of any previous studies that have assessed the biological efficacy of any ICCs, and encouragingly we found that the new speciation did not negatively affect established bioactivities of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics compared to lithium carbonate. Indeed, the studies detailed herein represent an important advancement in a crystal engineering approach to a new generation of lithium therapeutics. PMID:24191685

Improving lithium therapeutics by crystal engineering of novel ionic cocrystals.

PubMed

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

2013-12-02

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

Targeting Vasculature in Urologic Tumors: Mechanistic and Therapeutic Significance

PubMed Central

Sakamoto, Shinichi; Ryan, A. Jacqueline; Kyprianou, Natasha

2008-01-01

Recent advances toward understanding the molecular mechanisms regulating cancer initiation and progression provide new insights into the therapeutic value of targeting tumor vascularity by interfering with angiogenic signaling pathways. The functional contribution of key angiogenic factors toward increased vascularity characterizing metastatic tumors and their therapeutic exploitation is considered in three major urologic malignancies, renal, bladder, and prostate cancer. With the realization that the success of the therapeutic efficacy of the various anti-angiogenic approaches for the treatment of urologic tumors has yet to be proven clinically, the challenge remains to select critical angiogenesis pathways that can be targeted for an individual tumor. Here we discuss the major mechanisms that support formation of vasculature in renal, bladder, and prostate tumors and the current results of targeting of specific molecules/regulators for therapeutic intervention against metastastic disease. PMID:17668426

Review article: new drug formulations, chemical entities and therapeutic approaches for the management of ulcerative colitis.

PubMed

Ng, S C; Kamm, M A

2008-10-01

Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. 5-Aminosalicylic acids (5-ASA) remain the standard first-line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once-daily dosing, micropellet formulations,and high-dose tablets offer enhanced efficacy and improved compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator activated receptor-gamma (PPAR-gamma) and it has a role as a chemo-preventive agent in long-standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti-inflammatory targeted therapies include an anti-CD3 antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-gamma agonists. The evolution of novel oral 5-ASA formulations and dosage regimens,and recent development of new molecules have expanded the therapeutic armamentarium of UC.

The Therapeutic School.

ERIC Educational Resources Information Center

Rice, John Steadman

2002-01-01

Contributes to the recent research on specific institutional carriers of the therapeutic culture, such as the state, the corporation, and the self- help movement, defining therapeutic discourse and discussing the therapeutic ethic, the therapeutic school, schools of education and their critics, and disappointing results of therapeutic schooling.…

Phosphodiesterase-4 inhibition as a therapeutic approach to treat capillary leakage in systemic inflammation.

PubMed

Schick, Martin Alexander; Wunder, Christian; Wollborn, Jakob; Roewer, Norbert; Waschke, Jens; Germer, Christoph-Thomas; Schlegel, Nicolas

2012-06-01

In sepsis and systemic inflammation, increased microvascular permeability and consecutive breakdown of microcirculatory flow significantly contribute to organ failure and death. Evidence points to a critical role of cAMP levels in endothelial cells to maintain capillary endothelial barrier properties in acute inflammation. However, approaches to verify this observation in systemic models are rare. Therefore we tested here whether systemic application of the phosphodiesterase-4-inhibitors (PD-4-Is) rolipram or roflumilast to increase endothelial cAMP was effective to attenuate capillary leakage and breakdown of microcirculatory flow in severe lipopolysaccharide (LPS)-induced systemic inflammation in rats. Measurements of cAMP in mesenteric microvessels demonstrated significant LPS-induced loss of cAMP levels which was blocked by application of rolipram. Increased endothelial cAMP by application of either PD-4-I rolipram or roflumilast led to stabilization of endothelial barrier properties as revealed by measurements of extravasated FITC-albumin in postcapillary mesenteric venules. Accordingly, microcirculatory flow in mesenteric venules was significantly increased following PD-4-I treatment and blood gas analyses indicated improved metabolism. Furthermore application of PD-4-I after manifestation of LPS-induced systemic inflammation and capillary leakage therapeutically stabilized endothelial barrier properties as revealed by significantly reduced volume resuscitation for haemodynamic stabilization. Accordingly microcirculation was significantly improved following treatment with PD-4-Is. Our results demonstrate that inflammation-derived loss of endothelial cAMP contributes to capillary leakage which was blocked by systemic PD-4-I treatment. Therefore these data suggest a highly clinically relevant and applicable approach to stabilize capillary leakage in sepsis and systemic inflammation.

HIV therapeutic vaccines: moving towards a functional cure.

PubMed

Mylvaganam, Geetha H; Silvestri, Guido; Amara, Rama Rao

2015-08-01

Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV 'residual disease' that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vaccines (i.e., active immunization strategies using HIV-derived immunogens) as well as the use of checkpoint blockers such as anti-PD-1 antibodies. These approaches appear promising as key components of complex therapeutic strategies aimed at curing HIV infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer stem cell as therapeutic target for melanoma treatment.

PubMed

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.

A school peer mediation program as a context for exploring therapeutic jurisprudence (TJ): Can a peer mediation program inform the law?

PubMed

McWilliam, Nicky

2010-01-01

This paper reports an exploratory study of a school peer mediation program implemented as an alternative way to manage bullying and other destructive conflict. The study explores the effects of the program on the well-being of members of the school community by examining perceptions of students, staff and a sample of parents and former students. Drawing on therapeutic jurisprudence (TJ) the study explores whether the component parts of the program, separately or together, promote intended or unintended therapeutic effects. The preliminary findings of the study emphasise the importance of peer mediation training and suggest that existing scholarship in the area of school conflict resolution and peer mediation, when viewed through a TJ lens, may provide valuable insights into how to optimally configure programs for development and adoption in schools and other community settings. The study highlights the lack of attention paid by the legal system to valuable scholarship in the area of school conflict resolution and peer mediation, which may have implications for the understanding and development of legal processes and the law in general. Copyright © 2010 Elsevier Ltd. All rights reserved.

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites in tissue at therapeutic levels.

PubMed

Sun, Na; Walch, Axel

2013-08-01

Mass spectrometry imaging (MSI) is a rapidly evolving technology that yields qualitative and quantitative distribution maps of small pharmaceutical-active molecules and their metabolites in tissue sections in situ. The simplicity, high sensitivity and ability to provide comprehensive spatial distribution maps of different classes of biomolecules make MSI a valuable tool to complement histopathology for diagnostics and biomarker discovery. In this review, qualitative and quantitative MSI of drugs and metabolites in tissue at therapeutic levels are discussed and the impact of this technique in drug discovery and clinical research is highlighted.

Therapeutic Drug Monitoring and Clinical Outcomes in Immune Mediated Diseases: The Missing Link.

PubMed

Sorrentino, Dario; Nguyen, Vu; Henderson, Carl; Bankole, Adegabenga

2016-10-01

As the incidence of inflammatory bowel diseases and the number of patients treated with anti-TNF agents keep on increasing so are the phenomena of primary non response (PNR) and secondary loss of response (SLR) to these medications. Traditionally PNR and SLR have been managed empirically-that is, switching medications for PNR and increasing the anti-TNF dose for SNR. More recently an approach based on testing drug levels and antibodies to the drug (therapeutic drug monitoring) has gained increasing popularity in the management of inflammatory bowel diseases. However, while this strategy might offer an insight into the mechanisms leading to PNR/SLR it often falls short of providing a simple, reproducible method to manage these issues in clinical practice. Here, we will review the currently recommended therapeutic strategies when using therapeutic drug monitoring; the evidence for and against such approach and the current standard strategies in Rheumatology (the specialty with the largest and longest experience with anti-TNF agents). We will then discuss the possible reasons of the shortcomings of therapeutic drug monitoring and the rationale and need to move the therapeutic target to the disease burden in inflammatory bowel diseases-along with the supporting preliminary evidence. Finally, we will focus on future crucial studies that need to be done to make approaches to PNR/SLR more rigorous and at the same time user-friendly for the practicing gastroenterologist.

Design of portable valuables touch alarm circuit

NASA Astrophysics Data System (ADS)

Li, Biqing; Li, Zhao

2017-03-01

In this paper, the name of the alarm is portable touch burglar alarm. It not only has the advantages of high sensitivity, small size and light weight, but it is easy on the trigger, the circuit is simple and easy to be implemented, besides, it works stably. This alarm is featured with simple design, convenient use, strong flexibility and reliable performance, thus it can be installed on the door or window and even can be carried on human's body. When the human body touches the metal valuables that need to be protected, the device will start the alarm equipment so as to make the bell keep ringing, and the alarm sound stops until the power is cut off.

[Towards new therapeutic paradigms beyond symptom control in the management of inflammatory bowel diseases.

PubMed

Festa, Stefano; Zerboni, Giulia; Aratari, Annalisa; Ballanti, Riccardo; Papi, Claudio

2018-01-01

Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are chronic relapsing conditions that may result in progressive bowel damage, high risk of complications, surgery and permanent disability. The conventional therapeutic approach for inflammatory bowel diseases is based mainly on symptom control. Unfortunately, a symptom-based therapeutic approach has little impact on major long-term disease outcomes. In other chronic disabling conditions such as diabetes, hypertension and rheumatoid arthritis, the development of new therapeutic approaches has led to better outcomes. In this context a "treat to target" strategy has been developed. This strategy is based on identification of high-risk patients, regular assessment of disease activity by means of objective measures, adjustment of treatment to reach the pre-defined target. A treat to target approach has recently been proposed for inflammatory bowel disease with the aim at modifying the natural history of the disease. In this review, the evidence and the limitations of the treat to target paradigm in inflammatory bowel disease are analyzed and discussed.

Therapeutic vaccines for leishmaniasis.

PubMed

Khamesipour, Ali

2014-11-01

Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.

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

PubMed

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

2015-06-01

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

Recent advances in cancer therapeutics.

PubMed

Chessum, Nicola; Jones, Keith; Pasqua, Elisa; Tucker, Michael

2015-01-01

In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry. © 2015 Elsevier B.V. All rights reserved.

Real-time, aptamer-based tracking of circulating therapeutic agents in living animals

PubMed Central

Ferguson, B. Scott; Hoggarth, David A.; Maliniak, Dan; Ploense, Kyle; White, Ryan J.; Woodward, Nick; Hsieh, Kuangwen; Bonham, Andrew J.; Eisenstein, Michael; Kippin, Tod; Plaxco, Kevin W.; Soh, H. Tom

2014-01-01

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at sub-minute temporal resolution. Importantly, we show that MEDIC can also obtain pharmacokineticparameters for individual animals in real-time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters. PMID:24285484

Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies.

PubMed

Ponce, Rafael; Abad, Leslie; Amaravadi, Lakshmi; Gelzleichter, Thomas; Gore, Elizabeth; Green, James; Gupta, Shalini; Herzyk, Danuta; Hurst, Christopher; Ivens, Inge A; Kawabata, Thomas; Maier, Curtis; Mounho, Barbara; Rup, Bonita; Shankar, Gopi; Smith, Holly; Thomas, Peter; Wierda, Dan

2009-07-01

An evaluation of potential antibody formation to biologic therapeutics during the course of nonclinical safety studies and its impact on the toxicity profile is expected under current regulatory guidance and is accepted standard practice. However, approaches for incorporating this information in the interpretation of nonclinical safety studies are not clearly established. Described here are the immunological basis of anti-drug antibody formation to biopharmaceuticals (immunogenicity) in laboratory animals, and approaches for generating and interpreting immunogenicity data from nonclinical safety studies of biotechnology-derived therapeutics to support their progression to clinical evaluation. We subscribe that immunogenicity testing strategies should be adapted to the specific needs of each therapeutic development program, and data generated from such analyses should be integrated with available clinical and anatomic pathology, pharmacokinetic, and pharmacodynamic data to properly interpret nonclinical studies.

Pelvic belt effects on sacroiliac joint ligaments: a computational approach to understand therapeutic effects of pelvic belts.

PubMed

Sichting, Freddy; Rossol, Jerome; Soisson, Odette; Klima, Stefan; Milani, Thomas; Hammer, Niels

2014-01-01

The sacroiliac joint is a widely described source of low back pain. Therapeutic approaches to relieve pain include the application of pelvic belts. However, the effects of pelvic belts on sacroiliac joint ligaments as potential pain generators are mostly unknown. The aim of our study was to analyze the influence of pelvic belts on ligament load by means of a computer model. Experimental computer study using a finite element method. A computer model of the human pelvis was created, comprising bones, ligaments, and cartilage. Detailed geometries, material properties of ligaments, and in-vivo pressure distribution patterns of a pelvic belt were implemented. The effects of pelvic belts on ligament strain were computed in the double-leg stance. Pelvic belts increase sacroiliac joint motion around the sagittal axis but decrease motion around the transverse axis. With pelvic belt application, most of the strained sacroiliac joint ligaments were relieved, especially the sacrospinous, sacrotuberous, and the interosseous sacroiliac ligaments. Sacroiliac joint motion and ligament strains were minute. These results agree with validation data from other studies. Assigning homogenous and linear material properties and excluding muscle forces are clear simplifications of the complex reality. Pelvic belts alter sacroiliac joint motion and provide partial relief of ligament strain that is subjectively marked, although minimal in absolute terms. These findings confirm theories that besides being mechanical stabilizers, the sacroiliac joint ligaments are likely involved in neuromuscular feedback mechanisms. The results from our computer model help with unraveling the therapeutic mechanisms of pelvic belts.

Ethical dimensions of therapeutic human cloning.

PubMed

Reiss, Michael J

2002-09-11

Therapeutic human cloning has the potential significantly to reduce human suffering and enhance human happiness. This is the main ethical argument in its favour. The main ethical arguments against it centre on questions to do with the moral status of the human embryo. A subsidiary set of arguments arises from the connections between therapeutic human cloning and reproductive cloning. Most of the ethical questions concerning the status of the human embryo have long been examined in the context of abortion, though they are being re-examined in the context of genetic screening and embryo research. A consensus on such matters seems extremely unlikely to result in the near future. The current role of ethicists may not, therefore, be so much to attempt to produce a definitive answer to the question of the status of the human embryo at the very early developmental stages at which therapeutic human cloning would take place, but more to help clarify arguments and indicate the implications of particular approaches. That is what this paper seeks to do.

Market Orientation within University Schools of Business: Can a Dynamical Systems Viewpoint Applied to a Non-Temporal Data Set Yield Valuable Insights for University Managers?

ERIC Educational Resources Information Center

Cox, John C.; Webster, Robert L.; Hammond, Kevin L.

2009-01-01

This study investigates the use of using complexity theory--the study of nonlinear dynamical systems of which chaos and catastrophe theory are subsets--in the analysis of a non temporal data set to derive valuable insights into the functioning of university schools of business. The approach is unusual in that studies of nonlinearity in complex…

Imaging enabled platforms for development of therapeutics

NASA Astrophysics Data System (ADS)

Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2012-07-01

will in due course approach DOD for approval of the animal protocol. 15. SUBJECT TERMS Viral oncolysis, neoplastic meningitis , cell lines, HSV-1...proposed study is to develop novel, safe and efficient therapy for neoplastic meningitis – that of HSV-1 oncolysis. The viral genome is genetically...1 AD_________________ Award Number: W81XWH-11-1-0388 TITLE: Viral Oncolytic Therapeutics for Neoplastic

Novel therapeutic approaches for pulmonary fibrosis

PubMed Central

Datta, Arnab; Scotton, Chris J; Chambers, Rachel C

2011-01-01

Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis – median survival from the time of diagnosis is less than 3 years. This reflects the lack of any effective therapy to modify the course of the disease, which in turn is indicative of our incomplete understanding of the pathogenesis of this condition. Current prevailing hypotheses focus on dysregulated epithelial–mesenchymal interactions promoting a cycle of continued epithelial cell injury and fibroblast activation leading to progressive fibrosis. However, it is likely that multiple abnormalities in a myriad of biological pathways affecting inflammation and wound repair – including matrix regulation, epithelial reconstitution, the coagulation cascade, neovascularization and antioxidant pathways – modulate this defective crosstalk and promote fibrogenesis. This review aims to offer a pathogenetic rationale behind current therapies, briefly outlining previous and ongoing clinical trials, but will focus on recent and exciting advancements in our understanding of the pathogenesis of idiopathic pulmonary fibrosis, which may ultimately lead to the development of novel and effective therapeutic interventions for this devastating condition. LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1 PMID:21265830

High-intensity therapeutic ultrasound: metrological requirements versus clinical usage

NASA Astrophysics Data System (ADS)

Aubry, J.-F.

2012-10-01

High-intensity therapeutic ultrasound (HITU) is an appealing non-invasive, non-ionizing therapeutic modality with a wide range of tissue interactions ranging from transient permeabilization of cell membranes to thermal ablation. The ability to guide and monitor the treatment with an associated ultrasonic or magnetic resonance imaging device has resulted in a dramatic rise in the clinical use of therapeutic ultrasound in the past two decades. Nevertheless, the range of clinical applications and the number of patients treated has grown at a much higher pace than the definition of standards. In this paper the metrological requirements of the therapeutic beams are reviewed and are compared with the current clinical use of image-guided HITU mostly based on a practical approach. Liver therapy, a particularly challenging clinical application, is discussed to highlight the differences between some complex clinical situations and the experimental conditions of the metrological characterization of ultrasonic transducers.

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

PubMed

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.

Diagnostic and therapeutic value of laparoscopy for small bowel blunt injuries: A case report.

PubMed

Addeo, Pietro; Calabrese, Daniela Paola

2011-01-01

Small bowel injuries after blunt abdominal trauma represent both a diagnostic and a therapeutic challenge. Early diagnosis and prompt treatment are necessary in order to avoid a dangerous diagnostic delay. Laparoscopy can represent a diagnostic and therapeutic tool in patients with uncertain clinical symptoms. We report the case of a 25-year-old man, haemodynamically stable, admitted for acute abdominal pain a few hours after a physical assault. Giving the persistence of the abdominal pain and the presence of free fluids at the computed tomography examination, an exploratory laparoscopy was performed. At the laparoscopic exploration, an isolated small bowel perforation was found, 60 cm distal from the ligament of Treitz. The injury was repaired by laparoscopic suturing and the patient was discharged home at postoperative day 3 after an uneventful postoperative course. Laparoscopy represents a valuable tool for patients with small bowel blunt injuries allowing a timely diagnosis and a prompt treatment.

Therapeutic Approach to the Management of Severe Asymptomatic Hyponatremia.

PubMed

Ijaiya, Thaofiq; Manohar, Sandhya; Lakshmi, Kameswari

2017-01-01

Hyponatremia is an electrolyte imbalance encountered commonly in the hospital and ambulatory settings. It can be seen in isolation or present as a complication of other medical conditions. It is therefore a challenge to determine the appropriate therapeutic intervention. An understanding of the etiology is key in instituting the right treatment. Clinicians must not be too hasty to correct a random laboratory value without first understanding the physiologic principle. We present such a case of a patient who presented with sodium of 98 mmol/L, the lowest recorded in the current literature, and yet was asymptomatic. Following appropriate management driven by an understanding of the underlying pathophysiologic mechanism, the patient was managed to full recovery without any clinically significant neurological sequelae.

Mucocutaneous warts in Middle Anatolia, Turkey: clinical presentations and therapeutic approaches

PubMed Central

Gönül, Müzeyyen; Iyidal, Ayşegül Yalçınkaya; Çakmak, Seray; Kılıç, Arzu; Gul, Ulker; Doner, Pinar

2015-01-01

Introduction Viral warts are common skin condition caused by the human papilloma virus. Aim To determine the clinical features of warts and therapeutic approaches to warts and compare them with the literature. Material and methods A cross-sectional survey was conducted on 362 consecutive patients presenting to a dermatology clinic in Ankara, Middle Anatolia, Turkey. Age, gender, anatomic localization, clinical types, number of warts, and medical therapy histories were recorded. Results In our study 139 (38.4%) children and 223 (61.6%) adults had warts. Warts were seen in 191 men, and 171 women. The mean age was 24.7 ±13.5. In all groups the incidence and the number of warts were higher in men. Clinical types of warts were vulgar, anogenital, plantar, verruca plana, filiform, and mosaic. Thirty-six (9.9%) of 362 cases had more than one type. The locations of warts were as follows extremities (n = 233, 64.4%), anogenital (n = 86, 23.7%) and head and neck (n = 73, 20.2%). The incidence of anogenital warts was statistically higher in men than women (p < 0.05). Topical medical treatment was the first choice (n = 60, 57.1%). Conclusions In our study, the incidence and the number of warts were higher in men, which is different than in previous reports. The anogenital wart (AW) was ranked second in all types of warts. According to this finding, we can say that the frequency of AW has been increased in Turkey. To our knowledge recently there have been no studies investigating the clinical features of viral warts in all ages in the literature. PMID:26161058

National Heart, Lung, and Blood Institute and the translation of cardiovascular discoveries into therapeutic approaches.

PubMed

Galis, Zorina S; Black, Jodi B; Skarlatos, Sonia I

2013-04-26

The molecular causes of ≈4000 medical conditions have been described, yet only 5% have associated therapies. For decades, the average time for drug development through approval has taken 10 to 20 years. In recent years, the serious challenges that confront the private sector have made it difficult to capitalize on new opportunities presented by advances in genomics and cellular therapies. Current trends are disturbing. Pharmaceutical companies are reducing their investments in research, and biotechnology companies are struggling to obtain venture funds. To support early-stage translation of the discoveries in basic science, the National Institutes of Health and the National Heart, Lung, and Blood Institute have developed new approaches to facilitating the translation of basic discoveries into clinical applications and will continue to develop a variety of programs that create teams of academic investigators and industry partners. The goal of these programs is to maximize the public benefit of investment of taxpayer dollars in biomedical research and to lessen the risk required for industry partners to make substantial investments. This article highlights several examples of National Heart, Lung, and Blood Institute-initiated translational programs and National Institutes of Health translational resources designed to catalyze and enable the earliest stages of the biomedical product development process. The translation of latest discoveries into therapeutic approaches depends on continued federal funding to enhance the early stages of the product development process and to stimulate and catalyze partnerships between academia, industry, and other sources of capital.

Protein and peptide-based therapeutics in periodontal regeneration.

PubMed

Reynolds, Mark A; Aichelmann-Reidy, Mary E

2012-09-01

Protein and peptide-based therapeutics provide a unique strategy for controlling highly specific and complex biologic actions that cannot be accomplished by simple devices or chemical compounds. This article reviews some of the key characteristics and summarizes the clinical effectiveness of protein and peptide-based therapeutics targeting periodontal regeneration. A literature search was conducted of randomized clinical trials and systematic reviews evaluating protein and peptide-based therapeutics for the regeneration of periodontal tissues of at least 6 months duration. Data sources included PubMed and Embase electronic databases, hand-searched journals, and the ClinicalTrials.gov registry. Commercially marketed protein and peptide-based therapeutics for periodontal regeneration provide gains in clinical attachment level and bone formation that are comparable or superior to other regenerative approaches. Results from several clinical trials indicate that protein and peptide-based therapies can accelerate repair and regeneration when compared with other treatments and that improvements in clinical parameters continue beyond 12 months. Protein and peptide-based therapies also exhibit the capacity to increase the predictability of treatment outcomes. Clinical and histologic studies support the effectiveness of protein- and peptide-based therapeutics for periodontal regeneration. Emerging evidence suggests that the delivery devices/scaffolds play a critical role in determining the effectiveness of this class of therapeutics. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical research and the development of medical therapeutics.

PubMed

Antman, Elliott M

2014-01-01

Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion. Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine. Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development. The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system. They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs. Neither of these paths is desirable for future development of therapeutics. We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology). Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system.

A Cellular High-Throughput Screening Approach for Therapeutic trans-Cleaving Ribozymes and RNAi against Arbitrary mRNA Disease Targets

PubMed Central

Yau, Edwin H.; Butler, Mark C.; Sullivan, Jack M.

2016-01-01

Major bottlenecks in development of therapeutic post transcriptional gene silencing (PTGS) agents (e.g. ribozymes, RNA interference, antisense) include the challenge of mapping rare accessible regions of the mRNA target that are open for annealing and cleavage, testing and optimization of agents in human cells to identify lead agents, testing for cellular toxicity, and preclinical evaluation in appropriate animal models of disease. Methods for rapid and reliable cellular testing of PTGS agents are needed to identify potent lead candidates for optimization. Our goal was to develop a means of rapid assessment of many RNA agents to identify a lead candidate for a given mRNA associated with a disease state. We developed a rapid human cell-based screening platform to test efficacy of hammerhead ribozyme (hhRz) or RNA interference (RNAi) constructs, using a model retinal degeneration target, human rod opsin (RHO) mRNA. The focus is on RNA Drug Discovery for diverse retinal degeneration targets. To validate the approach, candidate hhRzs were tested against NUH↓ cleavage sites (N=G,C,A,U; H=C,A,U) within the target mRNA of secreted alkaline phosphatase (SEAP), a model gene expression reporter, based upon in silico predictions of mRNA accessibility. HhRzs were embedded in a larger stable adenoviral VAI RNA scaffold for high cellular expression, cytoplasmic trafficking, and stability. Most hhRz expression plasmids exerted statistically significant knockdown of extracellular SEAP enzyme activity when readily assayed by a fluorescence enzyme assay intended for high throughput screening (HTS). Kinetics of PTGS knockdown of cellular targets is measureable in live cells with the SEAP reporter. The validated SEAP HTS platform was transposed to identify lead PTGS agents against a model hereditary retinal degeneration target, RHO mRNA. Two approaches were used to physically fuse the model retinal gene target mRNA to the SEAP reporter mRNA. The most expedient way to evaluate a

The Expanding Therapeutic Utility of Botulinum Neurotoxins

PubMed Central

Fonfria, Elena; Maignel, Jacquie; Lezmi, Stephane; Martin, Vincent; Splevins, Andrew; Shubber, Saif; Kalinichev, Mikhail; Foster, Keith; Picaut, Philippe; Krupp, Johannes

2018-01-01

Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present an overview of the current therapeutic landscape and explore the diversity of BoNT proteins as future therapeutics. In recent years, novel indications have emerged in the fields of pain, migraine, overactive bladder, osteoarthritis, and wound healing. The study of biological effects distal to the injection site could provide future opportunities for disease-tailored BoNT therapies. However, there are some challenges in the pharmaceutical development of BoNTs, such as liquid and slow-release BoNT formulations; and, transdermal, transurothelial, and transepithelial delivery. Innovative approaches in the areas of formulation and delivery, together with highly sensitive analytical tools, will be key for the success of next generation BoNT clinical products. PMID:29783676

Neurocognitive therapeutics: from concept to application in the treatment of negative attention bias.

PubMed

Schnyer, David M; Beevers, Christopher G; deBettencourt, Megan T; Sherman, Stephanie M; Cohen, Jonathan D; Norman, Kenneth A; Turk-Browne, Nicholas B

2015-01-01

There is growing interest in the use of neuroimaging for the direct treatment of mental illness. Here, we present a new framework for such treatment, neurocognitive therapeutics. What distinguishes neurocognitive therapeutics from prior approaches is the use of precise brain-decoding techniques within a real-time feedback system, in order to adapt treatment online and tailor feedback to individuals' needs. We report an initial feasibility study that uses this framework to alter negative attention bias in a small number of patients experiencing significant mood symptoms. The results are consistent with the promise of neurocognitive therapeutics to improve mood symptoms and alter brain networks mediating attentional control. Future work should focus on optimizing the approach, validating its effectiveness, and expanding the scope of targeted disorders.

Awareness levels about breast cancer risk factors, early warning signs, and screening and therapeutic approaches among Iranian adult women: a large population based study using latent class analysis.

PubMed

Tazhibi, Mahdi; Feizi, Awat

2014-01-01

Breast cancer (BC) continues to be a major cause of morbidity and mortality among women throughout the world and in Iran. Lack of awareness and early detection program in developing country is a main reason for escalating the mortality. The present research was conducted to assess the Iranian women's level of knowledge about breast cancer risk factors, early warning signs, and therapeutic and screening approaches, and their correlated determinants. In a cross-sectional study, 2250 women before participating at a community based screening and public educational program in an institute of cancer research in Isfahan, Iran, in 2012 were investigated using a self-administered questionnaire about risk factors, early warning signs, and therapeutic and screening approaches of BC. Latent class regression as a comprehensive statistical method was used for evaluating the level of knowledge and its correlated determinants. Only 33.2%, 31.9%, 26.7%, and 35.8% of study participants had high awareness levels about screening approaches, risk factors, early warning signs and therapeutic modalities of breast cancer, respectively, and majority had poor to moderate knowledge levels. Most effective predictors of high level of awareness were higher educational qualifications, attending in screening and public educational programs, personal problem, and family history of BC, respectively. Results of current study indicated that the levels of awareness among study population about key elements of BC are low. These findings reenforce the continuing need for more BC education through conducting public and professional programs that are intended to raise awareness among younger, single women and those with low educational attainments and without family history.

Health care provider communication: an empirical model of therapeutic effectiveness.

PubMed

Chochinov, Harvey M; McClement, Susan E; Hack, Thomas F; McKeen, Nancy A; Rach, Amanda M; Gagnon, Pierre; Sinclair, Shane; Taylor-Brown, Jill

2013-05-01

Patients who are facing life-threatening and life-limiting cancer almost invariably experience psychological distress. Responding effectively requires therapeutic sensitivity and skill. In this study, we examined therapeutic effectiveness within the setting of cancer-related distress with the objective of understanding its constituent parts. Seventy-eight experienced psychosocial oncology clinicians from 24 health care centers across Canada were invited to participate in 3 focus groups each. In total, 29 focus groups were held over 2 years, during which clinicians articulated the therapeutic factors deemed most helpful in mitigating patient psychosocial distress. The content of each focus group was summarized into major themes and was reviewed with participants to confirm their accuracy. Upon completion of the focus groups, workshops were held in various centers, eliciting participant feedback on an empirical model of therapeutic effectiveness based on the qualitative analysis of focus group data. Three primary, interrelated therapeutic domains emerged from the data, forming a model of optimal therapeutic effectiveness: 1) personal growth and self-care (domain A), 2) therapeutic approaches (domain B), and 3) creation of a safe space (domain C). Areas of domain overlap were identified and labeled accordingly: domain AB, therapeutic humility; domain BC, therapeutic pacing; and domain AC, therapeutic presence. This empirical model provides detailed insights regarding the elements and pedagogy of effective communication and psychosocial care for patients who are experiencing cancer-related distress. Copyright © 2012 American Cancer Society.

Active targeted delivery of immune therapeutics to lymph nodes.

PubMed

Bahmani, Baharak; Vohra, Ishaan; Kamaly, Nazila; Abdi, Reza

2018-02-01

Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.

Novel therapeutic approaches for pulmonary arterial hypertension: Unique molecular targets to site-specific drug delivery.

PubMed

Vaidya, Bhuvaneshwar; Gupta, Vivek

2015-08-10

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disorder characterized by increased blood pressure in the small arterioles supplying blood to lungs for oxygenation. Advances in understanding of molecular and cellular biology techniques have led to the findings that PAH is indeed a cascade of diseases exploiting multi-faceted complex pathophysiology, with cellular proliferation and vascular remodeling being the key pathogenic events along with several cellular pathways involved. While current therapies for PAH do provide for amelioration of disease symptoms and acute survival benefits, their full therapeutic potential is hindered by patient incompliance and off-target side effects. To overcome the issues related with current therapy and to devise a more selective therapy, various novel pathways are being investigated for PAH treatment. In addition, inability to deliver anti-PAH drugs to the disease site i.e., distal pulmonary arterioles has been one of the major challenges in achieving improved patient outcomes and improved therapeutic efficacy. Several novel carriers have been explored to increase the selectivity of currently approved anti-PAH drugs and to act as suitable carriers for the delivery of investigational drugs. In the present review, we have discussed potential of various novel molecular pathways/targets including RhoA/Rho kinase, tyrosine kinase, endothelial progenitor cells, vasoactive intestinal peptide, and miRNA in PAH therapeutics. We have also discussed various techniques for site-specific drug delivery of anti-PAH therapeutics so as to improve the efficacy of approved and investigational drugs. This review will provide gainful insights into current advances in PAH therapeutics with an emphasis on site-specific drug payload delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Diagnostic and therapeutic approach to hypothalamic amenorrhea.

PubMed

Genazzani, Alessandro D; Ricchieri, Federica; Lanzoni, Chiara; Strucchi, Claudia; Jasonni, Valerio M

2006-12-01

Hypothalamic amenorrhea (HA) is a secondary amenorrhea with no evidence of endocrine/systemic causal factors, mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stress conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be exclude any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stress situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This article tries to give insights into diagnosis and putative therapeutic strategies.

Long-term delivery of protein therapeutics.

PubMed

Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-03-01

Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

Converting environmental risks to benefits by using spent coffee grounds (SCG) as a valuable resource.

PubMed

Stylianou, Marinos; Agapiou, Agapios; Omirou, Michalis; Vyrides, Ioannis; Ioannides, Ioannis M; Maratheftis, Grivas; Fasoula, Dionysia

2018-06-02

Coffee is perhaps one of the most vital ingredients in humans' daily life in modern world. However, this causes the production of million tons of relevant wastes, i.e., plastic cups, aluminum capsules, coffee chaff (silver skin), and spent coffee grounds (SCG), all thrown untreated into landfills. It is estimated that 1 kg of instant coffee generates around 2 kg of wet SCG; a relatively unique organic waste stream, with little to no contamination, separated directly in the source by the coffee shops. The produced waste has been under researchers' microscope as a useful feedstock for a number of promising applications. SCG is considered a valuable, nutrients rich source of bioactive compounds (e.g., phenolics, flavonoids, carotenoids, lipids, chlorogenic and protocatechuic acid, melanoidins, diterpenes, xanthines, vitamin precursors, etc.) and a useful resource material in other processes (e.g., soil improver and compost, heavy metals absorbent, biochar, biodiesel, pellets, cosmetics, food, and deodorization products). This paper aims to provide a holistic approach for the SCG waste management, highlighting a series of processes and applications in environmental solutions, food industry, and agricultural sector. Thus, the latest developments and approaches of SCG waste management are reviewed and discussed.

Approaches to Teaching Foreign Languages.

ERIC Educational Resources Information Center

Hesse, M. G., Ed.

Works by European and American educators from the Renaissance to the twentieth century are presented. A historical re-evaluation of foreign-language teaching combined with the scientific approach of modern linguistics can provide valuable insights for current teaching and learning approaches. Selections are presented from the writings of the…

Ofuji disease: a rare dermatosis and its challenging therapeutic approach*

PubMed Central

de Brito, Fernanda Freitas; Martelli, Antonio Carlos Ceribelli; Cavalcante, Maria Lopes Lamenha Lins; Pinto, Ana Cecília Versiani Duarte; Itimura, Gabriela; Soares, Cleverson Teixeira

2016-01-01

Eosinophilic pustular folliculitis (EPF) or Ofuji disease is a rare dermatosis, prone to recurrence and chronicity. The peak incidence occurs in the third decade of life and its exact etiology remains unknown. Evidence suggests that the expression of adhesion molecules and the production of cytokines activate the follicular unit, but the stimulus that triggers these changes remains unclear. The three clinical variants reported in the literature include classic EPF, immunosuppression-associated EPF, and infancy-associated EPF. We report a case of eosinophilic pustular folliculitis with peculiar epidemiological characteristics, which represents a challenging therapeutic scenario. PMID:27828641

Mechanisms of atherosclerosis and cardiovascular disease in antiphospholipid syndrome and systemic lupus erythematosus. New therapeutic approaches.

PubMed

Lopez-Pedrera, Chary; Aguirre-Zamorano, M Ángeles; Pérez-Sánchez, Carlos

2017-08-22

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are 2 highly related autoimmune-rheumatic diseases associated with an increased risk of developing cardiovascular (CV) diseases. Despite the great progresses made in understanding the pathological mechanisms leading to CV diseases in those pathologies, there is still the unmet need to improve long term prognosis. CV diseases in SLE and APS is thought to happen as the result of a complex interaction between traditional CV risk factors, immune deregulation and disease activity, including the synergic effect of cytokines, chemokines, adipokines, proteases, autoantibodies, adhesion receptors, oxidative stress and a plethora of intracellular signalling molecules. Genomic and epigenomic analyses have further allowed the identification of specific signatures explaining the proathero-thrombotic profiles of APS and SLE patients. This review examines the complex role of these heterogeneous factors, and analyses new therapeutic approaches under study to reduce the CV risk in these autoimmune disorders. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Human cells: new platform for recombinant therapeutic protein production.

PubMed

Swiech, Kamilla; Picanço-Castro, Virgínia; Covas, Dimas Tadeu

2012-07-01

The demand for recombinant therapeutic proteins is significantly increasing. There is a constant need to improve the existing expression systems, and also developing novel approaches to face the therapeutic proteins demands. Human cell lines have emerged as a new and powerful alternative for the production of human therapeutic proteins because this expression system is expected to produce recombinant proteins with post translation modifications more similar to their natural counterpart and reduce the potential immunogenic reactions against nonhuman epitopes. Currently, little information about the cultivation of human cells for the production of biopharmaceuticals is available. These cells have shown efficient production in laboratory scale and represent an important tool for the pharmaceutical industry. This review presents the cell lines available for large-scale recombinant proteins production and evaluates critically the advantages of this expression system in comparison with other expression systems for recombinant therapeutic protein production. Copyright © 2012 Elsevier Inc. All rights reserved.

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications

PubMed Central

Kratz, Jeremy D.; Chaddha, Ashish; Bhattacharjee, Somnath

2016-01-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID:26809711

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

PubMed

Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

2016-02-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

Stimuli-responsive nanomaterials for therapeutic protein delivery.

PubMed

Lu, Yue; Sun, Wujin; Gu, Zhen

2014-11-28

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

Stimuli-Responsive Nanomaterials for Therapeutic Protein Delivery

PubMed Central

Lu, Yue; Sun, Wujin; Gu, Zhen

2014-01-01

Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. PMID:25151983

Residential therapeutic communities for female substance abusers.

PubMed Central

De Leon, G.; Jainchill, N.

1991-01-01

Therapeutic communities provide a unique model for the needs of chemically dependent mothers who are pregnant or of child bearing age. These programs have been treating female addicts, many of whom reflect the profile and needs of the current generation of addicted mothers in clinical problems, social disadvantages, and poor socialization. Specific issues of their recovery can be most efficiently addressed in a residential community that provides housing and a comprehensive approach including medical, social, psychological care, parental training, and child care. Most evident is that these women need a lifestyle change, an opportunity for maturation. In this regard, the therapeutic community offers the essential element of community as a setting for learning right living. PMID:1868279

[There once was a child of divorce: story-telling and retelling as a pedagogic-therapeutic tool for younger school children in coping with the experiences of separation and divorce].

PubMed

Bünder, P

2000-04-01

The author shows that a rearranged narrative as a pedagogical and therapeutic means to help younger pupils coming to terms with the experiences of separation and divorce. Examples given demonstrate that this method can be a valuable help for these children to cope with their anxiety.

Personalized gene silencing therapeutics for Huntington disease.

PubMed

Kay, C; Skotte, N H; Southwell, A L; Hayden, M R

2014-07-01

Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non-selective silencing of both copies. Huntington disease (HD) is an autosomal dominant disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin gene (HTT). Silencing both expanded and normal copies of HTT may be therapeutically beneficial, but preservation of normal HTT expression is preferred. Allele-specific methods can selectively silence the mutant HTT transcript by targeting either the expanded CAG repeat or single nucleotide polymorphisms (SNPs) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of HD by CAG- and SNP-specific silencing approaches and review HD population genetics used to guide target identification in the patient population. Clinical implementation of allele-specific HTT silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunogenicity of therapeutics: a matter of efficacy and safety.

PubMed

Nechansky, Andreas; Kircheis, Ralf

2010-11-01

The unwanted immunogenicity of therapeutic proteins is a major concern regarding patient safety. Furthermore, pharmacokinetic, pharmacodynamic and clinical efficacy can be seriously affected by the immunogenicity of therapeutic proteins. Authorities have fully recognized this issue and demand appropriate and well-characterized assays to detect anti-drug antibodies (ADAs). We provide an overview of the immunogenicity topic in general, the regulatory background and insight into underlying immunological mechanisms and the limited ability to predict clinical immunogenicity a priori. Furthermore, we comment on the analytical testing approach and the status-quo of appropriate method validation. The review provides insight regarding the analytical approach that is expected by regulatory authorities overseeing immunogenicity testing requirements. Additionally, the factors influencing immunogenicity are summarized and key references regarding immunogenicity testing approaches and method validation are discussed. The unwanted immunogenicity of protein therapeutics is of major concern because of its potential to affect patient safety and drug efficacy. Analytical testing is sophisticated and requires more than one assay. Because immunogenicity in humans is hardly predictable, assay development has to start in a timely fashion and for clinical studies immunogenicity assay validation is mandatory prior to analyzing patient serum samples. Regarding ADAs, the question remains as to when such antibodies are regarded of clinical relevance and what levels are, if at all, acceptable. In summary, the detection of ADAs should raise the awareness of the physician concerning patient safety and of the sponsor/manufacture concerning the immunogenic potential of the drug product.

QUALITY ASSURANCE PROJECT PLANS: A USELESS PAPER EXERCISE OR VALUABLE AID?

EPA Science Inventory

Two perspectives on the fundamental question "Are quality assurance project plans (QAPPS) a useless paper exercise or a valuable aid?" will be explored. These perspectives include those of a Branch Chief (i.e., the supervisor/manager) and an active researcher. As a Branch Chief, ...

Evaluation of genotoxicity testing of FDA approved large molecule therapeutics.

PubMed

Sawant, Satin G; Fielden, Mark R; Black, Kurt A

2014-10-01

Large molecule therapeutics (MW>1000daltons) are not expected to enter the cell and thus have reduced potential to interact directly with DNA or related physiological processes. Genotoxicity studies are therefore not relevant and typically not required for large molecule therapeutic candidates. Regulatory guidance supports this approach; however there are examples of marketed large molecule therapeutics where sponsors have conducted genotoxicity studies. A retrospective analysis was performed on genotoxicity studies of United States FDA approved large molecule therapeutics since 1998 identified through the Drugs@FDA website. This information was used to provide a data-driven rationale for genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99 therapeutics identified were tested for genotoxic potential. None of the therapeutics tested showed a positive outcome in any study except the peptide glucagon (GlucaGen®) showing equivocal in vitro results, as stated in the product labeling. Scientific rationale and data from this review indicate that testing of a majority of large molecule modalities do not add value to risk assessment and support current regulatory guidance. Similarly, the data do not support testing of peptides containing only natural amino acids. Peptides containing non-natural amino acids and small molecules in conjugated products may need to be tested. Copyright © 2014 Elsevier Inc. All rights reserved.

Recovering valuable metals from recycled photovoltaic modules.

PubMed

Yi, Youn Kyu; Kim, Hyun Soo; Tran, Tam; Hong, Sung Kil; Kim, Myong Jun

2014-07-01

Recovering valuable metals such as Si, Ag, Cu, and Al has become a pressing issue as end-of-life photovoltaic modules need to be recycled in the near future to meet legislative requirements in most countries. Of major interest is the recovery and recycling of high-purity silicon (> 99.9%) for the production of wafers and semiconductors. The value of Si in crystalline-type photovoltaic modules is estimated to be -$95/kW at the 2012 metal price. At the current installed capacity of 30 GW/yr, the metal value in the PV modules represents valuable resources that should be recovered in the future. The recycling of end-of-life photovoltaic modules would supply > 88,000 and 207,000 tpa Si by 2040 and 2050, respectively. This represents more than 50% of the required Si for module fabrication. Experimental testwork on crystalline Si modules could recover a > 99.98%-grade Si product by HNO3/NaOH leaching to remove Al, Ag, and Ti and other metal ions from the doped Si. A further pyrometallurgical smelting at 1520 degrees C using CaO-CaF2-SiO2 slag mixture to scavenge the residual metals after acid leaching could finally produce > 99.998%-grade Si. A process based on HNO3/NaOH leaching and subsequent smelting is proposed for recycling Si from rejected or recycled photovoltaic modules. Implications: The photovoltaic industry is considering options of recycling PV modules to recover metals such as Si, Ag, Cu, Al, and others used in the manufacturing of the PV cells. This is to retain its "green" image and to comply with current legislations in several countries. An evaluation of potential resources made available from PV wastes and the technologies used for processing these materials is therefore of significant importance to the industry. Of interest are the costs of processing and the potential revenues gained from recycling, which should determine the viability of economic recycling of PV modules in the future.

Potential Therapeutic Benefits of Strategies Directed to Mitochondria

PubMed Central

Lesnefsky, Edward J.; Stowe, David F.

2010-01-01

Abstract The mitochondrion is the most important organelle in determining continued cell survival and cell death. Mitochondrial dysfunction leads to many human maladies, including cardiovascular diseases, neurodegenerative disease, and cancer. These mitochondria-related pathologies range from early infancy to senescence. The central premise of this review is that if mitochondrial abnormalities contribute to the pathological state, alleviating the mitochondrial dysfunction would contribute to attenuating the severity or progression of the disease. Therefore, this review will examine the role of mitochondria in the etiology and progression of several diseases and explore potential therapeutic benefits of targeting mitochondria in mitigating the disease processes. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate and manipulate mitochondrial function and genomics for therapeutic benefit. These approaches to treat mitochondrial dysfunction rationally could lead to selective protection of cells in different tissues and various disease states. However, most of these approaches are in their infancy. Antioxid. Redox Signal. 13, 279–347. PMID:20001744

Immunogenicity assessment during the development of protein therapeutics.

PubMed

Rosenberg, Amy S; Sauna, Zuben E

2018-05-01

Here we provide a critical review of the state of the art with respect to non-clinical assessments of immunogenicity for therapeutic proteins. The number of studies on immunogenicity published annually has more than doubled in the last 5 years. The science and technology, which have reached a critical mass, provide multiple of non-clinical approaches (computational, in vitro, ex vivo and animal models) to first predict and then to modify or eliminate T-cell or B-cell epitopes via de-immunization strategies. We discuss how these may be used in the context of drug development in assigning the immunogenicity risk of new and marketed therapeutic proteins. Protein therapeutics represents a large share of the pharma market and provide medical interventions for some of the most complex and intractable diseases. Immunogenicity (the development of antibodies to therapeutic proteins) is an important concern for both the safety and efficacy of protein therapeutics as immune responses may neutralize the activity of life-saving and highly effective protein therapeutics and induce hypersensitivity responses including anaphylaxis. The non-clinical computational tools and experimental technologies that offer a comprehensive and increasingly accurate estimation of immunogenic potential are surveyed here. This critical review also discusses technologies which are promising but are not as yet ready for routine use. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Hypothalamic amenorrhea: from diagnosis to therapeutical approach.

PubMed

Genazzani, A D; Chierchia, E; Santagni, S; Rattighieri, E; Farinetti, A; Lanzoni, C

2010-05-01

Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies. Copyright 2010 Elsevier Masson SAS. All rights reserved.

In vivo imaging of protease activity by Probody therapeutic activation

PubMed Central

Wong, Kenneth R.; Menendez, Elizabeth; Craik, Charles S.; Kavanaugh, W. Michael; Vasiljeva, Olga

2017-01-01

Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment. PMID:26546838

Determinants of immunogenic response to protein therapeutics.

PubMed

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

2012-09-01

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

Therapeutic gene editing: delivery and regulatory perspectives.

PubMed

Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

2017-06-01

Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues.

Therapeutic gene editing: delivery and regulatory perspectives

PubMed Central

Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

2017-01-01

Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues. PMID:28392568

[Limitation of therapeutic effort: Approach to a combined view].

PubMed

Bueno Muñoz, M J

2013-01-01

Over the past few decades, we have been witnessing that increasing fewer people pass away at home and increasing more do so within the hospital. More specifically, 20% of deaths now occur in an intensive care unit (ICU). However, death in the ICU has become a highly technical process. This sometimes originates excesses because the resources used are not proportionate related to the purposes pursued (futility). It may create situations that do not respect the person's dignity throughout the death process. It is within this context that the situation of the clinical procedure called "limitation of the therapeutic effort" (LTE) is reviewed. This has become a true bridge between Intensive Care and Palliative Care. Its final goal is to guarantee a dignified and painless death for the terminally ill. Copyright © 2012 Elsevier España, S.L. y SEEIUC. All rights reserved.

Wildlife as valuable natural resources vs. intolerable pests: A suburban wildlife management model

USGS Publications Warehouse

DeStefano, S.; Deblinger, R.D.

2005-01-01

Management of wildlife in suburban environments involves a complex set of interactions between both human and wildlife populations. Managers need additional tools, such as models, that can help them assess the status of wildlife populations, devise and apply management programs, and convey this information to other professionals and the public. We present a model that conceptualizes how some wildlife populations can fluctuate between extremely low (rare, threatened, or endangered status) and extremely high (overabundant) numbers over time. Changes in wildlife abundance can induce changes in human perceptions, which continually redefine species as a valuable resource to be protected versus a pest to be controlled. Management programs thatincorporate a number of approaches and promote more stable populations of wildlife avoid the problems of the resource versus pest transformation, are less costly to society, and encourage more positive and less negative interactions between humans and wildlife. We presenta case example of the beaver Castor canadensis in Massachusetts to illustrate how this model functions and can be applied. ?? 2005 Springer Science + Business Media, Inc.

From Stool Transplants to Next-generation Microbiota Therapeutics

PubMed Central

2014-01-01

The epidemic of Clostridium difficile infection fueled by new virulent strains of the organism has led to increased use of fecal microbiota transplantation (FMT). The procedure is effective for even the most desperate cases, after failure of multiple courses of antibiotics. The approach recognizes microbiota to be integral to normal human physiology, and microbiota being used in FMT represents a new class of therapeutics. Imbalance in the composition and altered activity of the microbiota are associated with many diseases. Consequently, there is growing interest in applying FMT to non-C. difficile indications. However, this may succeed only if microbiota therapeutics are developed systematically, based on mechanistic understanding, and applying updo-date principles of microbial ecology. We discuss two pathways in development of this new therapeutic class: whole microbial communities separated from donor stool and an assembly of specific fecal microorganisms grown in vitro. PMID:24412527

Targeted delivery of miRNA therapeutics for cardiovascular diseases: opportunities and challenges.

PubMed

Kwekkeboom, Rick F J; Lei, Zhiyong; Doevendans, Pieter A; Musters, René J P; Sluijter, Joost P G

2014-09-01

Dysregulation of miRNA expression has been associated with many cardiovascular diseases in animal models, as well as in patients. In the present review, we summarize recent findings on the role of miRNAs in cardiovascular diseases and discuss the opportunities, possibilities and challenges of using miRNAs as future therapeutic targets. Furthermore, we focus on the different approaches that can be used to deliver these newly developed miRNA therapeutics to their sites of action. Since siRNAs are structurally homologous with the miRNA therapeutics, important lessons learned from siRNA delivery strategies are discussed that might be applicable to targeted delivery of miRNA therapeutics, thereby reducing costs and potential side effects, and improving efficacy.

Systematic review of the diagnosis of scabies in therapeutic trials.

PubMed

Thompson, M J; Engelman, D; Gholam, K; Fuller, L C; Steer, A C

2017-07-01

Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies. © 2017 British Association of Dermatologists.

Germ cell transplantation using sexually competent fish: an approach for rapid propagation of endangered and valuable germlines.

PubMed

Majhi, Sullip K; Hattori, Ricardo S; Yokota, Masashi; Watanabe, Seiichi; Strüssmann, Carlos A

2009-07-02

The transplantation of germ cells into adult recipient gonads is a tool with wide applications in animal breeding and conservation of valuable and/or endangered species; it also provides a means for basic studies involving germ cell (GC) proliferation and differentiation. Here we describe the establishment of a working model for xenogeneic germ cell transplantation (GCT) in sexually competent fish. Spermatogonial cells isolated from juveniles of one species, the pejerrey Odontesthes bonariensis (Atherinopsidae), were surgically transplanted into the gonads of sexually mature Patagonian pejerrey O. hatcheri, which have been partially depleted of endogenous GCs by a combination of Busulfan (40 mg/kg) and high water temperature (25 degrees C) treatments. The observation of the donor cells' behavior showed that transplanted spermatogonial cells were able to recolonize the recipients' gonads and resume spermatogenesis within 6 months from the GCT. The presence of donor-derived gametes was confirmed by PCR in 20% of the surrogate O. hatcheri fathers at 6 months and crosses with O. bonariensis mothers produced hybrids and pure O. bonariensis, with donor-derived germline transmission rates of 1.2-13.3%. These findings indicate that transplantation of spermatogonial cells into sexually competent fish can shorten considerably the production time of donor-derived gametes and offspring and could play a vital role in germline conservation and propagation of valued and/or endangered fish species.

Therapeutic Potential of Phytochemicals in Combination with Drugs for Cardiovascular Disorders.

PubMed

Shen, James Z; Ng, Ting L J; Ho, Wing S

2017-01-01

The incidence of cardiovascular disorders is increasing worldwide. Heart disease is the leading cause of death for both men and women. High blood pressure, high low-density lipoprotein cholesterol level, and smoking are key risk factors for heart disease. Other medical conditions such as diabetes, overweight, obesity and lifestyle can put people at a higher risk for coronary heart disease. The preventive measures based on the common drugs may help reduce the risk of cardiovascular diseases. The present review highlights the contributions of therapeutic potential of phytochemicals in management of cardiovascular diseases. However, the delivery efficiency of therapeutic agents can be enhanced in order to improve the efficacy of phytochemicals as a therapeutic agent. The oral administration of phytochemicals as therapeutic agents is a common approach. The review highlights the recent development of natural products for the complementary treatment of cardiovascular diseases. These findings indicate that the combination of therapeutic drugs and natural products may improve the treatment efficacy of therapeutic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Challenges in the development of magnetic particles for therapeutic applications.

PubMed

Barry, Stephen E

2008-09-01

Certain iron-based particle formulations have useful magnetic properties that, when combined with low toxicity and desirable pharmacokinetics, encourage their development for therapeutic applications. This mini-review begins with background information on magnetic particle use as MRI contrast agents and the influence of material size on pharmacokinetics and tissue penetration. Therapeutic investigations, including (1) the loading of bioactive materials, (2) the use of stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles in tissues or to separate material bound to the particles from the body, and (3) the application of high power alternating magnetic fields (AMF) to generate heat in magnetic particles for hyperthermic therapeutic applications are then surveyed. Attention is directed mainly to cancer treatment, as selective distribution to tumors is well-suited to particulate approaches and has been a focus of most development efforts. While magnetic particles have been explored for several decades, their use in therapeutic products remains minimal; a discussion of future directions and potential ways to better leverage magnetic properties and to integrate their use into therapeutic regimens is discussed.

Recognition and Distance in Therapeutic Education: A Swedish Case Study on Ethical Qualities within Life Competence Education

ERIC Educational Resources Information Center

Irisdotter Aldenmyr, Sara

2013-01-01

Lately, in educational research and debate, there have been discussions on a trend sometimes named as a "therapeutic turn" in education. Mindfulness-oriented activities represent one therapeutic approach in education, aiming for virtues such as patience and trust. A large part of the critical viewpoints on therapeutic education among…

Therapeutic bond judgments: Congruence and incongruence.

PubMed

Atzil-Slonim, Dana; Bar-Kalifa, Eran; Rafaeli, Eshkol; Lutz, Wolfgang; Rubel, Julian; Schiefele, Ann-Kathrin; Peri, Tuvia

2015-08-01

The present study had 2 aims: (a) to implement West and Kenny's (2011) Truth-and-Bias model to simultaneously assess the temporal congruence and directional discrepancy between clients' and therapists' ratings of the bond facet of the therapeutic alliance, as they cofluctuate from session to session; and (b) to examine whether symptom severity and a personality disorder (PD) diagnosis moderate congruence and/or discrepancy. Participants included 213 clients treated by 49 therapists. At pretreatment, clients were assessed for a PD diagnosis and completed symptom measures. Symptom severity was also assessed at the beginning of each session, using client self-reports. Both clients and therapists rated the therapeutic bond at the end of each session. Therapists and clients exhibited substantial temporal congruence in their session-by-session bond ratings, but therapists' ratings tended to be lower than their clients' across sessions. Additionally, therapeutic dyads whose session-by-session ratings were more congruent also tended to have a larger directional discrepancy (clients' ratings being higher). Pretreatment symptom severity and PD diagnosis did not moderate either temporal congruence or discrepancy at the dyad level; however, during sessions when clients were more symptomatic, therapist and client ratings were both farther apart and tracked each other less closely. Our findings are consistent with a "better safe than sorry" pattern, which suggests that therapists are motivated to take a vigilant approach that may lead both to underestimation and to attunement to fluctuations in the therapeutic bond. (c) 2015 APA, all rights reserved).

CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma

PubMed Central

Bhatt, Shruti; Ashlock, Brittany M.; Natkunam, Yasodha; Sujoy, Victoria; Chapman, Jennifer Rose; Ramos, Juan Carlos; Mesri, Enrique A.; Lossos, Izidore S.

2013-01-01

Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi’s sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients. PMID:23838350

Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches

PubMed Central

Joseph, Biny K.; Thakali, Keshari M.; Moore, Christopher L.; Rhee, Sung W.

2013-01-01

Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells (VSMCs). The dynamic interplay of Ca2+ and K+ channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles. The abnormally-elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca2+ and K+ channels in the VSMCs. In this short review, we focus on the three well-studied ion channels in VSMCs, namely the L-type Ca2+ (CaV1.2) channels, the voltage-gated K+ (KV) channels, and the large-conductance Ca2+-activated K+ (BK) channels. First, we provide a brief overview on the physiological role of vascular CaV1.2, KV and BK channels in regulating arterial tone. Second, we discuss the current understanding of the expression changes and regulation of CaV1.2, KV and BK channels in the vasculature during hypertension. Third, based on available proof-of-concept studies, we describe the potential therapeutic approaches targeting these vascular ion channels in order to restore blood pressure to normotensive levels. PMID:23376354

The potential therapeutic value for bereaved relatives participating in research: An exploratory study.

PubMed

Germain, Alison; Mayland, Catriona R; Jack, Barbara A

2016-10-01

Conducting research with the bereaved presents an immediate ethical challenge, as they are undoubtedly a vulnerable group, associated with high levels of distress and susceptible to both physical and mental health issues. A comprehensive understanding of the potential therapeutic benefits for bereaved relatives participating in palliative care research is limited, and therefore the ethics of engaging this group remain questionable. This paper describes a secondary analysis of qualitative data collected in the Care of the Dying Evaluation (CODE) project, examining the experiences of patients who died at home. It explores the motivations and potential benefits for bereaved relatives participating in research with reference to the recently developed concepts in bereavement theory. Cognitive interviews were conducted with 15 bereaved relatives and secondary analysis using a content analysis framework was employed to classify the data. The results center around six recurring concepts identified as adaptive in current bereavement theory: an opportunity to share the narrative accounts of the final hours of their relative's life; a search for sense and meaning in loss; an ongoing bond/attachment with the deceased; altruistic motivations; oscillation between loss and restorative orientations; and a sense of resilience. Overall, the participants found that taking part in the research was valuable and that it could be described as offering therapeutic benefits. The need for bereaved relatives to take part in research studies should be encouraged, as they provide an accurate proxy for the patient's experience of end-of-life care while also providing a valuable account of their own perspective as family member and carer. In addition, we highlight the need for ethics committees to be aware of the potential benefits for bereaved relatives participating in research of this kind.

Towards new uses of botulinum toxin as a novel therapeutic tool.

PubMed

Pickett, Andy; Perrow, Karen

2011-01-01

The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

Therapeutic and diagnostic challenges for frontotemporal dementia

PubMed Central

D’Alton, Simon; Lewis, Jada

2014-01-01

In the search for therapeutic modifiers, frontotemporal dementia (FTD) has traditionally been overshadowed by other conditions such as Alzheimer’s disease (AD). A clinically and pathologically diverse condition, FTD has been galvanized by a number of recent discoveries such as novel genetic variants in familial and sporadic forms of disease and the identification of TAR DNA binding protein of 43 kDa (TDP-43) as the defining constituent of inclusions in more than half of cases. In combination with an ever-expanding knowledge of the function and dysfunction of tau—a protein which is pathologically aggregated in the majority of the remaining cases—there exists a greater understanding of FTD than ever before. These advances may indicate potential approaches for the development of hypothetical therapeutics, but FTD remains highly complex and the roles of tau and TDP-43 in neurodegeneration are still wholly unclear. Here the challenges facing potential therapeutic strategies are discussed, which include sufficiently accurate disease diagnosis and sophisticated technology to deliver effective therapies. PMID:25191265

Long-Term Delivery of Protein Therapeutics

PubMed Central

Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-01-01

Introduction Proteins are effective biotherapetics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. Areas covered This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Expert opinion Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery related issues. A large number of protein molecules are under clinical trials and hence there is an urgent need to develop new methods to deliver these highly potent biologics. PMID:25251334

Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.

PubMed

Carmeli, Y; Akova, M; Cornaglia, G; Daikos, G L; Garau, J; Harbarth, S; Rossolini, G M; Souli, M; Giamarellou, H

2010-02-01

Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

A bottom-up approach to assess verbal therapeutic techniques. Development of the Psychodynamic Interventions List (PIL)

PubMed Central

Gumz, Antje; Neubauer, Karolin; Horstkotte, Julia Katharina; Geyer, Michael; Löwe, Bernd; Murray, Alexandra M.; Kästner, Denise

2017-01-01

Objective Knowing which specific verbal techniques “good” therapists use in their daily work is important for training and evaluation purposes. In order to systematize what is being practiced in the field, our aim was to empirically identify verbal techniques applied in psychodynamic sessions and to differentiate them according to their basic semantic features using a bottom-up, qualitative approach. Method Mixed-Method-Design: In a comprehensive qualitative study, types of techniques were identified at the level of utterances based on transcribed psychodynamic therapy sessions using Qualitative Content Analysis (4211 utterances). The definitions of the identified categories were successively refined and modified until saturation was achieved. In a subsequent quantitative study, inter-rater reliability was assessed both at the level of utterances (n = 8717) and at the session level (n = 38). The convergent validity of the categories was investigated by analyzing associations with the Interpretive and Supportive Technique Scale (ISTS). Results The inductive approach resulted in a classification system with 37 categories (Psychodynamic Interventions List, PIL). According to their semantic content, the categories can be allocated to three dimensions: form (24 categories), thematic content (9) and temporal focus (4). Most categories showed good or excellent inter-rater reliability and expected associations with the ISTS were predominantly confirmed. The rare use of the residual category “Other” suggests that the identified categories might comprehensively describe the breadth of applied techniques. Conclusions The atheoretical orientation and the clear focus on overt linguistic features should enable the PIL to be used without intensive training or prior theoretical knowledge. The PIL can be used to investigate the links between verbal techniques derived from practice and micro-outcomes (at the session level) as well as the overall therapeutic outcomes. This

Pathophysiological aspects and therapeutic approaches of tumoral osteolysis and hypercalcemia.

PubMed

Bonjour, J P; Rizzoli, R

1989-01-01

Malignant tumors can affect the integrity of the skeletal tissue and the homeostasis of the two main components of bone mineral, calcium (Ca) and inorganic phosphate (Pi). Various tumoral cell products can increase bone resorption by influencing the number of osteoclasts and/or their activity. These tumoral products could act either directly on bone cells of the osteoblastic or osteoclastic lineages, or indirectly by influencing cells secreting osteotropic factors, such as interleukin-1, tumor necrosis factors, transforming growth factors, and colony-stimulating factor. Among the classical calciotropic hormones, 1,25-dihydroxyvitamin D3 could be implicated in lymphoma. In hypercalcemia of malignancy, an increase in bone resorption is observed in most patients. However, in many cases an increased tubular reabsorption of Ca has been documented as well. This phenomenon when present after adequate rehydration is probably due to the secretion by the tumoral cells of a parathyroid hormone-related peptide (PTHrP). This factor has been recently identified as a protein containing 141 amino acids. This protein or some very close analogs have been shown to be secreted by lung, kidney and also breast carcinoma. Besides increasing bone resorption and stimulating tubular reabsorption of Ca, PTHrP also selectively decreases the tubular reabsorption of Pi, an action that may explain the hypophosphatemia observed in some types of neoplasm. Therapeutically, administration of antiresorbing agents such as clodronate or other bisphosphonates can normalize the increased osteolysis and, if present, the associated elevation in the plasma level of Ca in most cancer patients. However in some cases, wherein the prevailing hypercalcemic mechanism is due to an enhancement in the tubular reabsorption of Ca, other therapeutic means should be associated with the antiosteolytic bisphosphonate therapy.

Therapeutic drug approach to stimulate clinical recovery after brain injury.

PubMed

Krieger, Derk W

2013-01-01

The identification of strategies by which the central nervous system (CNS) can transform itself in response to injury has incited the systematic exploration of methods to enhance neurological recovery after CNS injury. Several pharmaceuticals have been shown to promote such recovery; however, more rigorous clinical trials are necessary to establish their clinical relevance. The major impediment for these strategies in the clinical arena is the astounding heterogeneity surrounding neuroplasticity and regeneration. Tolerance to injury and varied rates of recovery are likely governed by genetic and environmental factors that remain largely elusive. The extraordinary complexity of the neural networks in the CNS impedes the assessment of 'plain' pharmacological interventions in therapeutic trials. 'Proof-of-principle' studies of pharmacological interventions enhancing neuroplasticity or regeneration may therefore at first focus on surrogate markers, such as functional MRI, magnetoencephalography and diffusion tensor imaging, or investigate seemingly more uniform systems, such as spinal cord injuries. The discovery that experimental adult CNS lesions can essentially regenerate has rejected the conviction that adult axon injury is always permanent and spurred research into determining whether the circumstances under which such regeneration occurs can be created in human CNS injury. The hostility of the microenvironment preventing axonal regrowth has been linked to key molecular targets involving myelin-associated factors and glial scar components. While the mechanisms involved are better understood now and potential therapeutic targets are identified, the crucial question whether manipulating the molecular regulation of axonal repair is feasible and will benefit patients remains uncertain. While factual repair of brain tissue may still be years away, research into the mechanisms of adaptation after brain injury offers more tangible return on the short run. Copyright �

Therapeutic approaches for treating hemophilia A using embryonic stem cells.

PubMed

Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko

2016-06-01

Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Therapeutic synthetic gene networks.

PubMed

Karlsson, Maria; Weber, Wilfried

2012-10-01

The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment-oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Therapeutic interventions for hypertension in metabolic syndrome: a comprehensive approach.

PubMed

Ganne, Sudha; Arora, Surender; Karam, Jocelyne; McFarlane, Samy I

2007-03-01

Hypertension is a major component of the metabolic syndrome and a major cardiovascular risk factor. Both disorders are rapidly increasing in frequency, with hypertension affecting nearly 60 million Americans and over 1 billion people worldwide, and metabolic syndrome affecting 44% of the US population above the age of 60 years. Sedentary lifestyle, together with obesity and aging of the population, are the major contributing factors for this growing epidemic. Hypertension in metabolic syndrome possesses unique pathophysiological aspects that have considerable implications on therapy of this disease. In this article, we review the pathophysiology and provide a rationale for the current therapeutic options in light of the most recent clinical trials in the field.

Therapeutic applications of CRISPR RNA-guided genome editing.

PubMed

Koo, Taeyoung; Kim, Jin-Soo

2017-01-01

The rapid development of programmable nuclease-based genome editing technologies has enabled targeted gene disruption and correction both in vitro and in vivo This revolution opens up the possibility of precise genome editing at target genomic sites to modulate gene function in animals and plants. Among several programmable nucleases, the type II clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated nuclease 9 (Cas9) system has progressed remarkably in recent years, leading to its widespread use in research, medicine and biotechnology. In particular, CRISPR-Cas9 shows highly efficient gene editing activity for therapeutic purposes in systems ranging from patient stem cells to animal models. However, the development of therapeutic approaches and delivery methods remains a great challenge for biomedical applications. Herein, we review therapeutic applications that use the CRISPR-Cas9 system and discuss the possibilities and challenges ahead. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Biosecurity strategies for conserving valuable livestock genetic resources.

PubMed

Wrathall, Anthony E; Simmons, Hugh A; Bowles, Dianna J; Jones, Sam

2004-01-01

The foot and mouth disease (FMD) epidemic in the UK in 2001 highlighted the threat of infectious diseases to rare and valuable livestock and stimulated a renewed interest in biosecurity and conservation. However, not all diseases resemble FMD: their transmission routes and pathological effects vary greatly, so biosecurity strategies must take this into account. Realism is also needed as to which diseases to exclude and which will have to be tolerated. The aim should be to minimise disease generally and to exclude those diseases that threaten the existence of livestock or preclude their national or international movement. Achieving this requires a team effort, bearing in mind the livestock species involved, the farming system ('open' or 'closed') and the premises. Effective biosecurity demands that practically every aspect of farm life is controlled, including movements of people, vehicles, equipment, food, manure, animal carcasses and wildlife. Above all, biosecurity strategies must cover the disease risks associated with moving the livestock themselves and this will require quarantine if adult or juvenile animals are imported into the herd or flock. The present paper emphasises the important role that reproductive technologies, such as artificial insemination and embryo transfer, can have in biosecurity strategies because they offer much safer ways for getting new genetic materials into herds/flocks than bringing in live animals. Embryo transfer is especially safe when the sanitary protocols promoted by the International Embryo Transfer Society and advocated by the Office International des Epizooties (the 'World Organisation for Animal Health') are used. Embryo transfer can also allow the full genetic complement to be salvaged from infected animals. Cryobanking of genetic materials, especially embryos, is another valuable biosecurity strategy because it enables their storage for conservation in the face of contingencies, such as epidemic disease and other

Countertransference reactions in therapeutic work with incestuous sexual abusers.

PubMed

Friedrich, Monika; Leiper, Rob

2006-01-01

The study was a qualitative investigation aimed at therapists' responses to working with a population of incestuous sexual abusers. Semi-structured interviews were conducted with nine therapists who were recruited from psychotherapy, psychology, and forensic psychology services in the National Health Service (NHS) in the UK. The predominant therapeutic model was psychodynamic; however, cognitive-behavioural and integrative approaches were practiced by some therapists. The data were analyzed using interpretative phenomenological analysis (Smith, 1996). Results suggested that the therapists experienced a considerable amount of negative and difficult feelings and that they tended to experience feeling controlled and deceived, which seemed to influence their ability to create and maintain the therapeutic relationship. It was suggested that the dynamics of incestuous sexual abuse played a part in these difficulties. The results are discussed with reference to the clinical therapeutic literature.

Side Streams of Plant Food Processing As a Source of Valuable Compounds: Selected Examples.

PubMed

Schieber, Andreas

2017-02-28

Industrial processing of plant-derived raw materials generates enormous amounts of by-products. On one hand, these by-products constitute a serious disposal issue because they often emerge seasonally and are prone to microbial decay. On the other hand, they are an abundant source of valuable compounds, in particular secondary plant metabolites and cell wall materials, which may be recovered and used to functionalize foods and replace synthetic additives with ingredients of natural origin. This review covers 150 references and presents select studies performed between 2001 and 2016 on the recovery, characterization, and application of valuable constituents from grape pomace, apple pomace, potato peels, tomato pomace, carrot pomace, onion peels, by-products of citrus, mango, banana, and pineapple processing, side streams of olive oil production, and cereal by-products. The criteria used were economic importance, amounts generated, relevance of side streams as a source of valuable compounds, and reviews already published. Despite a plethora of studies carried out on the utilization of side streams, relatively few processes have yet found industrial application.

Therapeutic Significance of Loligo vulgaris (Lamarck, 1798) ink Extract: A Biomedical Approach.

PubMed

Nadarajah, Sri Kumaran; Vijayaraj, Radha; Mani, Jayaprakashvel

2017-12-01

The squid ink extract is well known for its biomedical properties. In this study, squid Loligo vulgaris was collected from Tuticorin costal water, Bay of Bengal, India. Proximate composition of the crude squid ink was studied and found to have protein as the major component over lipid and carbohydrates. Further, bioactive fractions of squid ink were extracted with ethanol, and therapeutic applications such as hemolytic, antioxidant, antimicrobial, and in vitro anti-inflammatory properties were analyzed using standard methods. In hemolytic assay, the squid ink extract exhibited a maximum hemolytic activity of 128 hemolytic unit against tested erythrocytes. In DPPH assay, the ethanolic extract of squid ink has exhibited an antioxidant activity of 83.5%. The squid ink was found to be potent antibacterial agent against the pathogens tested. 200 μL of L. vulgaris ink extract showed remarkable antibacterial activity as zone of inhibition against Escherichia coli (28 mm), Klebsiella pneumoniae (22 mm), Pseudomonas aeruginosa (21 mm), and Staphylococcus aureus (24 mm). The 68.9% inhibition of protein denaturation by the squid ink extract indicated that it has very good in vitro anti-inflammatory properties. The Fourier transform infrared spectroscopy analysis of the ethanolic extracts of the squid ink indicated the presence of functional groups such as 1° and 2° amines, amides, alkynes (terminal), alkenes, aldehydes, nitriles, alkanes, aliphatic amines, carboxylic acids, and alkyl halides, which complements the biochemical background of therapeutic applications. Hence, results of this study concluded that the ethanolic extract of L. vulgaris has many therapeutic applications such as antimicrobial, antioxidant, and anti-inflammatory activities. Squid ink is very high in a number of important nutrients. It's particularly high in antioxidants for instance, which as well all know help to protect the cells and the heart against damage from free radicals. In the present study

Positive allosteric modulators as an approach to nicotinic acetylcholine receptor- targeted therapeutics: advantages and limitations

PubMed Central

Williams, Dustin K.; Wang, Jingyi; Papke, Roger L.

2011-01-01

Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (agonists, partial agonists, competitive antagonists) at conventional agonist binding sites, but is also regulated in either negative or positive ways by the binding of ligands to other modulatory sites. In this review, we discuss models for the activation and desensitization of nAChR, and the discovery of multiple types of ligands that influence those processes in both heteromeric nAChR, such as the high affinity nicotine receptors of the brain, and homomeric α7-type receptors. In recent years, α7 nAChRs have been identified as a potential target for therapeutic indications leading to the development of α7-selective agonists and partial agonists. However, unique properties of α7 nAChR, including low probability of channel opening and rapid desensitization, may limit the therapeutic usefulness of ligands binding exclusively to conventional agonist binding sites. New enthusiasm for the therapeutic targeting of α7 has come from the identification of α7-selective positive allosteric modulators (PAMs) that work effectively on the intrinsic factors that limit α7 ion channel activation. While these new drugs appear promising for therapeutic development, we also consider potential caveats and possible limitations for their use, including PAM-insensitive forms of desensitization and cytotoxicity issues. PMID:21575610

Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.

PubMed

Williams, Dustin K; Wang, Jingyi; Papke, Roger L

2011-10-15

Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (agonists, partial agonists, competitive antagonists) at conventional agonist binding sites, but is also regulated in either negative or positive ways by the binding of ligands to other modulatory sites. In this review, we discuss models for the activation and desensitization of nAChR, and the discovery of multiple types of ligands that influence those processes in both heteromeric nAChR, such as the high-affinity nicotine receptors of the brain, and homomeric α7-type receptors. In recent years, α7 nAChRs have been identified as a potential target for therapeutic indications leading to the development of α7-selective agonists and partial agonists. However, unique properties of α7 nAChR, including low probability of channel opening and rapid desensitization, may limit the therapeutic usefulness of ligands binding exclusively to conventional agonist binding sites. New enthusiasm for the therapeutic targeting of α7 has come from the identification of α7-selective positive allosteric modulators (PAMs) that work effectively on the intrinsic factors that limit α7 ion channel activation. While these new drugs appear promising for therapeutic development, we also consider potential caveats and possible limitations for their use, including PAM-insensitive forms of desensitization and cytotoxicity issues. Copyright © 2011 Elsevier Inc. All rights reserved.

Establishment of a cell-based wound healing assay for bio-relevant testing of wound therapeutics.

PubMed

Planz, Viktoria; Wang, Jing; Windbergs, Maike

Predictive in vitro testing of novel wound therapeutics requires adequate cell-based bio-assays. Such assays represent an integral part during preclinical development as pre-step before entering in vivo studies. Simple "scratch tests" based on defected skin cell monolayers exist, however these can solely be used for testing liquids, as cell monolayer destruction and excessive hydration limit their applicability for (semi-)solid systems like wound dressings. In this context, a cell-based wound healing assay is introduced for rapid and predictive testing of wound therapeutics independent of their physical state in a bio-relevant environment. A novel wound healing assay was established for bio-relevant and predictive testing of (semi-) solid wound therapeutics. The assay allows for physiologically relevant hydration of the tested wound therapeutics at the air-liquid interface and their removal without cell monolayer disruption. In a proof-of-concept study, the applicability and discriminative power could be demonstrated by examining unloaded and drug-loaded wound dressings with two different established wound healing actives (dexpanthenol and metyrapone) and their effect on skin cell behavior. The influence of the released drug on the cells´ healing behavior could successfully be monitored over time. Wound size assessment after 96h resulted in an eight fold smaller wound area for drug treated models compared to the ones treated with unloaded fibers and non-treated wounds. This assay provides valuable first insights towards the establishment of a valid screening and evaluation tool for preclinical wound therapeutic development from liquid to (semi-)solid systems to improve predictability in a simple, yet standardized way. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent Development of Anticancer Therapeutics Targeting Akt

PubMed Central

Morrow, John K.; Du-Cuny, Lei; Chen, Lu; Meuillet, Emmanuelle J.; Mash, Eugene A.; Powis, Garth; Zhang, Shuxing

2013-01-01

The serine/threonine kinase Akt has proven to be a significant signaling target, involved in various biological functions. Because of its cardinal role in numerous cellular responses, Akt has been implicated in many human diseases, particularly cancer. It has been established that Akt is a viable and feasible target for anticancer therapeutics. Analysis of all Akt kinases reveals conserved homology for an N-terminal regulatory domain, which contains a pleckstrin-homology (PH) domain for cellular translocation, a kinase domain with serine/threonine specificity, and a C-terminal extension domain. These well defined regions have been targeted, and various approaches, including in silico methods, have been implemented to develop Akt inhibitors. In spite of unique techniques and a prolific body of knowledge surrounding Akt, no targeted Akt therapeutics have reached the market yet. Here we will highlight successes and challenges to date on the development of anticancer agents modulating the Akt pathway in recent patents as well as discuss the methods employed for this task. Special attention will be given to patents with focus on those discoveries using computer-aided drug design approaches. PMID:21110830

Nasal-nanotechnology: revolution for efficient therapeutics delivery.

PubMed

Kumar, Amrish; Pandey, Aditya Nath; Jain, Sunil Kumar

2016-01-01

In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.

Innovative Therapeutic Intervention for Children: Animal-Assisted Therapy in South Australia

ERIC Educational Resources Information Center

Jones, Mel

2018-01-01

Unique approaches are important to explore for every aspect of our work with children, including therapeutic support for traumatized children. Sometimes, these techniques involve inviting some furry friends into the classroom.

An augmented reality game to support therapeutic education for children with diabetes

PubMed Central

Calle-Bustos, Andrés-Marcelo; García-García, Inmaculada; Abad, Francisco

2017-01-01

Therapeutic education in diabetes helps patients take responsibility for self-control of their disease, and providing technological support systems facilitates this education. In this paper, we present an augmented reality game to support therapeutic education for patients with diabetes. Our game helps children (aged 5–14 years) to learn carbohydrate (carb) content of different foods. The game shows virtual foods on a real dish. The number of carb choices corresponding to the visualized food is also shown (1 carb choice = 10 grams of carbs). A study to determine the effectiveness of the game in terms of learning and perceived satisfaction and usability was carried out. A total of seventy children with diabetes participated in the study. From the results, we observed that the initial knowledge about carb choices of the children who participated in the study was low (a mean of 2 on a scale from 0 to 9). This indicates that therapeutic education for patients with diabetes is needed. When the results for the pre-knowledge questionnaire and the post-knowledge questionnaire were compared, it was shown that the children learned about carb choices by playing our game. We used two post-knowledge questionnaires (one post-knowledge questionnaire that contained the same foods as the pre-knowledge questionnaire and a second post-knowledge questionnaire that contained foods that were different from the ones on the pre-knowledge questionnaire). There were no statistically significant differences between these two different post-knowledge questionnaires. Moreover, the knowledge acquired was independent of gender and age. We also evaluated usability and perceived satisfaction. The children were satisfied with the game and considered that the game offers a high degree of usability. This game could be a valuable therapeutic education tool for patients with diabetes. PMID:28957355

An augmented reality game to support therapeutic education for children with diabetes.

PubMed

Calle-Bustos, Andrés-Marcelo; Juan, M-Carmen; García-García, Inmaculada; Abad, Francisco

2017-01-01

Therapeutic education in diabetes helps patients take responsibility for self-control of their disease, and providing technological support systems facilitates this education. In this paper, we present an augmented reality game to support therapeutic education for patients with diabetes. Our game helps children (aged 5-14 years) to learn carbohydrate (carb) content of different foods. The game shows virtual foods on a real dish. The number of carb choices corresponding to the visualized food is also shown (1 carb choice = 10 grams of carbs). A study to determine the effectiveness of the game in terms of learning and perceived satisfaction and usability was carried out. A total of seventy children with diabetes participated in the study. From the results, we observed that the initial knowledge about carb choices of the children who participated in the study was low (a mean of 2 on a scale from 0 to 9). This indicates that therapeutic education for patients with diabetes is needed. When the results for the pre-knowledge questionnaire and the post-knowledge questionnaire were compared, it was shown that the children learned about carb choices by playing our game. We used two post-knowledge questionnaires (one post-knowledge questionnaire that contained the same foods as the pre-knowledge questionnaire and a second post-knowledge questionnaire that contained foods that were different from the ones on the pre-knowledge questionnaire). There were no statistically significant differences between these two different post-knowledge questionnaires. Moreover, the knowledge acquired was independent of gender and age. We also evaluated usability and perceived satisfaction. The children were satisfied with the game and considered that the game offers a high degree of usability. This game could be a valuable therapeutic education tool for patients with diabetes.

Multirate delivery of multiple therapeutic agents from metal-organic frameworks

DOE PAGES

McKinlay, Alistair C.; Allan, Phoebe K.; Renouf, Catherine L.; ...

2014-12-01

The highly porous nature of metal-organic frameworks (MOFs) offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.

Delivery of RNAi Therapeutics to the Airways-From Bench to Bedside.

PubMed

Qiu, Yingshan; Lam, Jenny K W; Leung, Susan W S; Liang, Wanling

2016-09-20

RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.

[Anticancer drugs: Which prices for therapeutic innovations?].

PubMed

Gonçalves, Anthony; Maraninchi, Dominique; Marino, Patricia

2016-04-01

The expanding knowledge of the biological mechanisms underlying tumor development made it possible the recent emergence of new therapeutic approaches that are considered as undoubtedly innovative. Yet, to define and to evaluate the magnitude of a drug innovation require an examination of its intrinsic drug properties, medical utility as well as its mode of emergence. Recently, international academic societies, such as ESMO and ASCO, have proposed practical tools that may help quantifying the medical value of a given innovation. Currently, the sustained flux of therapeutic innovations in oncology is associated with an unprecedented growth of costs, the actual determinants of which remain under debate, but raising the critical issue of drugs pricing, and their potential individual or societal "financial toxicity". Copyright © 2016. Published by Elsevier Masson SAS.

Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities

PubMed Central

Wilber, Andrew; Nienhuis, Arthur W.

2011-01-01

In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels. PMID:21321359

A diagnostic and therapeutic approach to primary burning mouth syndrome.

PubMed

Moghadam-Kia, Siamak; Fazel, Nasim

Primary burning mouth syndrome (BMS) is an oral mucosal disorder that is characterized by a chronic and often debilitating intraoral burning sensation for which no localized or systemic cause can be found. BMS most commonly affects postmenopausal women. The pathophysiology of primary BMS is not well understood. Diagnosing BMS can prove to be challenging. BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients. Most commonly used therapies include tricyclic antidepressants, α-lipoic acid, clonazepam, and cognitive-behavioral therapy. Clinical judgment, patient counseling, and monitoring of pain are important. Further research is required to assess the effectiveness of serotonin and newer serotonin-noradrenalin reuptake inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

T-cell dependent immunogenicity of protein therapeutics: Preclinical assessment and mitigation.

PubMed

Jawa, Vibha; Cousens, Leslie P; Awwad, Michel; Wakshull, Eric; Kropshofer, Harald; De Groot, Anne S

2013-12-01

Protein therapeutics hold a prominent and rapidly expanding place among medicinal products. Purified blood products, recombinant cytokines, growth factors, enzyme replacement factors, monoclonal antibodies, fusion proteins, and chimeric fusion proteins are all examples of therapeutic proteins that have been developed in the past few decades and approved for use in the treatment of human disease. Despite early belief that the fully human nature of these proteins would represent a significant advantage, adverse effects associated with immune responses to some biologic therapies have become a topic of some concern. As a result, drug developers are devising strategies to assess immune responses to protein therapeutics during both the preclinical and the clinical phases of development. While there are many factors that contribute to protein immunogenicity, T cell- (thymus-) dependent (Td) responses appear to play a critical role in the development of antibody responses to biologic therapeutics. A range of methodologies to predict and measure Td immune responses to protein drugs has been developed. This review will focus on the Td contribution to immunogenicity, summarizing current approaches for the prediction and measurement of T cell-dependent immune responses to protein biologics, discussing the advantages and limitations of these technologies, and suggesting a practical approach for assessing and mitigating Td immunogenicity. © 2013. Published by Elsevier Inc. All rights reserved.

Use of Therapeutic Drug Monitoring, Electronic Health Record Data, and Pharmacokinetic Modeling to Determine the Therapeutic Index of Phenytoin and Lamotrigine

PubMed Central

Ku, Lawrence C.; Wu, Huali; Greenberg, Rachel G.; Hill, Kevin D.; Gonzalez, Daniel; Hornik, Christoph P.; Berezny, Alysha; Guptill, Jeffrey T.; Jiang, Wenlei; Zheng, Nan; Cohen-Wolkowiez, Michael; Melloni, Chiara

2016-01-01

Background Defining a drug's therapeutic index (TI) is important for patient safety and regulating the development of generic drugs. For many drugs, the TI is unknown. A systematic approach was developed to characterize the TI of a drug using therapeutic drug monitoring and electronic health record (EHR) data with pharmacokinetic (PK) modeling. This approach was first tested on phenytoin, which has a known TI, and then applied to lamotrigine, which lacks a defined TI. Methods Retrospective EHR data from patients in a tertiary hospital were used to develop phenytoin and lamotrigine population PK models and to identify adverse events (anemia, thrombocytopenia, and leukopenia) and efficacy outcomes (seizure-free). Phenytoin and lamotrigine concentrations were simulated for each day with an adverse event or seizure. Relationships between simulated concentrations and adverse events and efficacy outcomes were used to calculate the TI for phenytoin and lamotrigine. Results For phenytoin, 93 patients with 270 total and 174 free concentrations were identified. A de novo 1-compartment PK model with Michaelis-Menten kinetics described the data well. Simulated average total and free concentrations of 10-15 and 1.0-1.5 μg/mL were associated with both adverse events and efficacy in 50% of patients, resulting in a TI of 0.7–1.5. For lamotrigine, 45 patients with 53 concentrations were identified. A published 1-compartment model was adapted to characterize the PK data. No relationships between simulated lamotrigine concentrations and safety or efficacy endpoints were seen; therefore, the TI could not be calculated. Conclusions This approach correctly determined the TI of phenytoin but was unable to determine the TI of lamotrigine due to a limited sample size. The use of therapeutic drug monitoring and EHR data to aid in narrow TI drug classification is promising, but it requires an adequate sample size and accurate characterization of concentration–response relationships

Use of Therapeutic Drug Monitoring, Electronic Health Record Data, and Pharmacokinetic Modeling to Determine the Therapeutic Index of Phenytoin and Lamotrigine.

PubMed

Ku, Lawrence C; Wu, Huali; Greenberg, Rachel G; Hill, Kevin D; Gonzalez, Daniel; Hornik, Christoph P; Berezny, Alysha; Guptill, Jeffrey T; Jiang, Wenlei; Zheng, Nan; Cohen-Wolkowiez, Michael; Melloni, Chiara

2016-12-01

Defining a drug's therapeutic index (TI) is important for patient safety and regulating the development of generic drugs. For many drugs, the TI is unknown. A systematic approach was developed to characterize the TI of a drug using therapeutic drug monitoring and electronic health record (EHR) data with pharmacokinetic (PK) modeling. This approach was first tested on phenytoin, which has a known TI, and then applied to lamotrigine, which lacks a defined TI. Retrospective EHR data from patients in a tertiary hospital were used to develop phenytoin and lamotrigine population PK models and to identify adverse events (anemia, thrombocytopenia, and leukopenia) and efficacy outcomes (seizure-free). Phenytoin and lamotrigine concentrations were simulated for each day with an adverse event or seizure. Relationships between simulated concentrations and adverse events and efficacy outcomes were used to calculate the TI for phenytoin and lamotrigine. For phenytoin, 93 patients with 270 total and 174 free concentrations were identified. A de novo 1-compartment PK model with Michaelis-Menten kinetics described the data well. Simulated average total and free concentrations of 10-15 and 1.0-1.5 mcg/mL were associated with both adverse events and efficacy in 50% of patients, resulting in a TI of 0.7-1.5. For lamotrigine, 45 patients with 53 concentrations were identified. A published 1-compartment model was adapted to characterize the PK data. No relationships between simulated lamotrigine concentrations and safety or efficacy endpoints were seen; therefore, the TI could not be calculated. This approach correctly determined the TI of phenytoin but was unable to determine the TI of lamotrigine due to a limited sample size. The use of therapeutic drug monitoring and EHR data to aid in narrow TI drug classification is promising, but it requires an adequate sample size and accurate characterization of concentration-response relationships.

Mango (Mangifera indica L.) by-products and their valuable components: a review.

PubMed

Jahurul, M H A; Zaidul, I S M; Ghafoor, Kashif; Al-Juhaimi, Fahad Y; Nyam, Kar-Lin; Norulaini, N A N; Sahena, F; Mohd Omar, A K

2015-09-15

The large amount of waste produced by the food industries causes serious environmental problems and also results in economic losses if not utilized effectively. Different research reports have revealed that food industry by-products can be good sources of potentially valuable bioactive compounds. As such, the mango juice industry uses only the edible portions of the mangoes, and a considerable amount of peels and seeds are discarded as industrial waste. These mango by-products come from the tropical or subtropical fruit processing industries. Mango by-products, especially seeds and peels, are considered to be cheap sources of valuable food and nutraceutical ingredients. The main uses of natural food ingredients derived from mango by-products are presented and discussed, and the mainstream sectors of application for these by-products, such as in the food, pharmaceutical, nutraceutical and cosmetic industries, are highlighted. Copyright © 2015 Elsevier Ltd. All rights reserved.

The therapeutic value of adolescents' blogging about social-emotional difficulties.

PubMed

Boniel-Nissim, Meyran; Barak, Azy

2013-08-01

Research shows that writing a personal diary is a valuable therapeutic means for relieving emotional distress and promoting well-being, and that diary writing during adolescence helps in coping with developmental challenges. Current technologies and cultural trends make it possible and normative to publish personal diaries on the Internet through blogs--interactive, online forms of the traditional personal diary. We examined the therapeutic value of blogging for adolescents who experience social-emotional difficulties. The field experiment included randomly assigned adolescents, preassessed as having social-emotional difficulties, to 6 groups (26-28 participants in each): Four groups were assigned to blogging (writing about their difficulties or free writing; either open or closed to responses), a group assigned to writing a diary on personal computers, and a no-treatment control group. Participants in the 5 writing groups were instructed to post messages at least twice a week over 10 weeks. Outcome measures included scales of social-emotional difficulties and self-esteem, a social activities checklist, and textual analyses of participants' posts. Measurement took place at pre- and postintervention and at follow-up 2 months later. Results showed that participants maintaining a blog significantly improved on all measures. Participants writing about their difficulties in blogs open to responses gained the most. These results were consistent in the follow-up evaluation. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Vulvovaginal candidosis: contemporary challenges and the future of prophylactic and therapeutic approaches.

PubMed

Chew, Shu Yih; Than, Leslie Thian Lung

2016-05-01

Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal pathogen Candida species. In fact, three out of every four women will experience at least one occasion of VVC during some point in their lives. Although uncomplicated VVC is relatively harmless, the complicated VVC such as recurrent attack often creates restlessness and depression in the patients, thus greatly affects their quality of life. Managements of VVC are usually associated with the use of antimycotic suppositories, topical cream or oral agents. These antimycotic agents are either available over-the-counter or prescribed by the clinicians. In recent decades, the rise of clinical challenges such as the increased prevalence of resistant Candida strains, recurrent VVC infection and adverse effects of multidrug interactions have necessitated the development of novel therapeutic or prophylactic options to combat the complicated VVC in the future. In this review, we discuss the current antimycotic treatments available for Candida vaginitis and the problems that exist in these seemingly effective treatments. Besides, we attempt to contemplate some of the future and prospective strategies surrounding the development of alternative therapeutic and prophylactic options in treating and preventing complicated VVC respectively. © 2016 Blackwell Verlag GmbH.

Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach.

PubMed

Franquesa, Alba; Sainz-Cort, Alberto; Gandy, Sam; Soler, Joaquim; Alcázar-Córcoles, Miguel Ángel; Bouso, José Carlos

2018-06-01

Ayahuasca is a psychedelic decoction originating from Amazonia. The ayahuasca-induced introspective experience has been shown to have potential benefits in the treatment of several pathologies, to protect mental health and to improve neuropsychological functions and creativity, and boost mindfulness. The underlying psychological processes related to the use of ayahuasca in a psychotherapeutic context are not yet well described in the scientific literature, but there is some evidence to suggest that psychological variables described in psychotherapies could be useful in explaining the therapeutic effects of the brew. In this study we explore the link between ayahuasca use and Decentering, Values and Self, comparing subjects without experience of ayahuasca (n = 41) with subjects with experience (n = 81). Results confirm that ayahuasca users scored higher than non-users in Decentering and Positive self, but not in Valued living, Life fulfillment, Self in social relations, Self in close relations and General self. Scores in Decentering were higher in the more experienced subjects (more than 15 occasions) than in those with less experience (less than 15 occasions). Our results show that psychological process variables may explain the outcomes in ayahuasca psychotherapy. The introduction of these variables is warranted in future ayahuasca therapeutic studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Parasites as valuable stock markers for fisheries in Australasia, East Asia and the Pacific Islands.

PubMed

Lester, R J G; Moore, B R

2015-01-01

Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.

The Potential for Emerging Microbiome-Mediated Therapeutics in Asthma.

PubMed

Ozturk, Ayse Bilge; Turturice, Benjamin Arthur; Perkins, David L; Finn, Patricia W

2017-08-10

In terms of immune regulating functions, analysis of the microbiome has led the development of therapeutic strategies that may be applicable to asthma management. This review summarizes the current literature on the gut and lung microbiota in asthma pathogenesis with a focus on the roles of innate molecules and new microbiome-mediated therapeutics. Recent clinical and basic studies to date have identified several possible therapeutics that can target innate immunity and the microbiota in asthma. Some of these drugs have shown beneficial effects in the treatment of certain asthma phenotypes and for protection against asthma during early life. Current clinical evidence does not support the use of these therapies for effective treatment of asthma. The integration of the data regarding microbiota with technologic advances, such as next generation sequencing and omics offers promise. Combining comprehensive bioinformatics, new molecules and approaches may shape future asthma treatment.

[Customizing dosage drugs what contribution in therapeutic drug monitoring?].

PubMed

Abdessadek, Mohammed; Magoul, Rabia; Amarti, Afaf; El Ouezzani, Seloua; Khabbal, Youssef

2014-01-01

Drug response is often variable from an individual to another: the same dose of drug administered to different patients could cause variable pharmacological effects in nature and intensity. Those effects are often the result of variability in drugs pharmacokinetics (absorption, distribution, metabolism and elimination) which alter their bioavailability. In fact, two factors should be taken into account: the disease(s) from which the patient suffers, and the associated drugs, because many drug interactions may alter their pharmacokinetics causing consequently quite enough of different therapeutic effects. The choice of the assay of the drug subject in monitoring is crucial, it allows quantifying the in vivo dose of the drug and the quality of compliance thereof, the pharmacokinetic characteristics allows the clinician to adjust the dosage by different approaches so that plasma concentrations are included in the therapeutic range. Therapeutic monitoring aims to increase clinical efficacy and to minimize toxicity.

Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment.

PubMed

Phi, Lan Thi Hanh; Sari, Ita Novita; Yang, Ying-Gui; Lee, Sang-Hyun; Jun, Nayoung; Kim, Kwang Seock; Lee, Yun Kyung; Kwon, Hyog Young

2018-01-01

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer relapse due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Thus, it is important to understand the characteristics and mechanisms by which CSCs display resistance to therapeutic agents. In this review, we highlight the key features and mechanisms that regulate CSC function in drug resistance as well as recent breakthroughs of therapeutic approaches for targeting CSCs. This promises new insights of CSCs in drug resistance and provides better therapeutic rationales to accompany novel anticancer therapeutics.

New insights into the molecular pathophysiology of fragile X syndrome and therapeutic perspectives from the animal model.

PubMed

Busquets-Garcia, Arnau; Maldonado, Rafael; Ozaita, Andrés

2014-08-01

Fragile X syndrome is the most common monogenetic form of intellectual disability and is a leading cause of autism. This syndrome is produced by the reduced transcription of the fragile X mental retardation (FMR1) gene, and it is characterized by a range of symptoms heterogeneously expressed in patients such as cognitive impairment, seizure susceptibility, altered pain sensitivity and anxiety. The recent advances in the understanding of the pathophysiological mechanisms involved have opened novel potential therapeutic approaches identified in preclinical rodent models as a necessary preliminary step for the subsequent evaluation in patients. Among those possible therapeutic approaches, the modulation of the metabotropic glutamate receptor signaling or the GABA receptor signaling have focused most of the attention. New findings in the animal models open other possible therapeutic approaches such as the mammalian target of rapamycin signaling pathway or the endocannabinoid system. This review summarizes the emerging data recently obtained in preclinical models of fragile X syndrome supporting these new therapeutic perspectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improving Therapeutic Relationships: Joint Crisis Planning for Individuals With Psychotic Disorders.

PubMed

Farrelly, Simone; Lester, Helen; Rose, Diana; Birchwood, Max; Marshall, Max; Waheed, Waquas; Henderson, R Claire; Szmukler, George; Thornicroft, Graham

2015-12-01

Outcomes for individuals with psychosis remain far from acceptable. Recently, prominent psychiatrists have called for an improved understanding of the impact of social contexts, and how social contexts might influence the development and maintenance of mental health problems. A key social context for individuals with psychosis is the therapeutic relationship. As part of a trial of joint crisis planning in England, this qualitative study aimed to determine the mechanism through which joint crisis planning might affect the therapeutic relationship. Results suggest that routine processes in mental health care are affected by policy and organizational requirements for risk mitigation-aspects that undermine person-centered approaches. In contrast, strong therapeutic relationships are characterized by individualized care and reliable and respectful treatment. The Joint Crisis Plan intervention partially succeeded in reducing contextual influences on routine role enactments, facilitating the demonstration of respect and improving the therapeutic relationship. © The Author(s) 2015.

Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as promising therapeutic targets in neurodegeneration and neurotrauma.

PubMed

Raad, Mohamad; El Tal, Tala; Gul, Rukhsana; Mondello, Stefania; Zhang, Zhiqun; Boustany, Rose-Mary; Guingab, Joy; Wang, Kevin K; Kobeissy, Firas

2012-12-01

Several common degenerative mechanisms and mediators underlying the neuronal injury pathways characterize several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease, as well as brain neurotrauma. Such common ground invites the emergence of new approaches and tools to study the altered pathways involved in neural injury alongside with neuritogenesis, an intricate process that commences with neuronal differentiation. Achieving a greater understanding of the impaired pathways of neuritogenesis would significantly help in uncovering detailed mechanisms of axonal regeneration. Among the several agents involved in neuritogenesis are the Rho and Rho kinases (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is known to be disrupted in multiple neuropathologies such as spinal cord injury, traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK inhibition as a promising candidate for therapeutic targets for treatment of neurodegenerative diseases. Among the novel tools to investigate the mechanisms involved in a specific disorder is the use of neuroproteomics/systems biology approach, a growing subfield of bioinformatics aiming to study and establishing a global assessment of the entire neuronal proteome, addressing the dynamic protein changes and interactions. This review aims to examine recent updates regarding how neuroproteomics aids in the understanding of molecular mechanisms of activation and inhibition in the area of neurogenesis and how Rho/ROCK pathway/ROCK inhibitors, primarily Y-27632 and Fasudil compounds, are applied in biological settings, promoting neuronal survival and neuroprotection that has direct future implications in neurotrauma. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Complex adaptive therapeutic strategy (CATS) for cancer.

PubMed

Cho, Yong Woo; Kim, Sang Yoon; Kwon, Ick Chan; Kim, In-San

2014-02-10

Tumors begin with a single cell, but as each tumor grows and evolves, it becomes a wide collection of clones that display remarkable heterogeneity in phenotypic features, which has posed a big challenge to current targeted anticancer therapy. Intra- and inter-tumoral heterogeneity is attributable in part to genetic mutations but also to adaptation and evolution of tumors to heterogeneity in tumor microenvironments. If tumors are viewed not only as a disease but also as a complex adaptive system (CAS), tumors should be treated as such and a more systemic approach is needed. Some of many tumors therapeutic strategies are discussed here from a view of a tumor as CAS, which can be collectively called a complex adaptive therapeutic strategy (CATS). The central theme of CATS is based on three intermediate concepts: i) disruption of artifacts, ii) disruption of connections, and iii) reprogramming of cancer-immune dynamics. Each strategy presented here is a piece of the puzzle for CATS. Although each piece by itself may be neither novel nor profound, an assembled puzzle could be a novel and innovative cancer therapeutic strategy. Copyright © 2013 Elsevier B.V. All rights reserved.

Emerging nanotechnology based strategies for diagnosis and therapeutics of urinary tract infections: A review.

PubMed

Kumar, M S; Das, A P

2017-11-01

At present, various diagnostic and therapeutic approaches are available for urinary tract infections. But, still the quest for development of more rapid, accurate and reliable approach is an unending process. The pathogens, especially uropathogens are adapting to new environments and antibiotics day by day rapidly. Therefore, urinary tract infections are evolving as hectic and difficult to eradicate, increasing the economic burden to the society. The technological advances should be able to compete the adaptability characteristics of microorganisms to combat their growth in new environments and thereby preventing their infections. Nanotechnology is at present an extensively developing area of immense scientific interest since it has diverse potential applications in biomedical field. Nanotechnology may be combined with cellular therapy approaches to overcome the limitations caused by conventional therapeutics. Nanoantibiotics and drug delivery using nanotechnology are currently growing areas of research in biomedical field. Recently, various categories of antibacterial nanoparticles and nanocarriers for drug delivery have shown their potential in the treatment of infectious diseases. Nanoparticles, compared to conventional antibiotics, are more beneficial in terms of decreasing toxicity, prevailing over resistance and lessening costs. Nanoparticles present long term therapeutic effects since they are retained in body for relatively longer periods. This review focuses on recent advances in the field of nanotechnology, principally emphasizing diagnostics and therapeutics of urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB.

PubMed

Martins, Marta

2011-05-01

The emergence of resistance in tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca(2+) and K(+) flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).

A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system.

PubMed

Zennami, Kenji; Yoshikawa, Kazuhiro; Kondo, Eisaku; Nakamura, Kogenta; Upsilonamada, Yoshiaki; De Velasco, Marco A; Tanaka, Motoyoshi; Uemura, Hirotsugu; Shimazui, Toru; Akaza, Hideyuki; Saga, Shinsuke; Ueda, Ryuzo; Honda, Nobuaki

2011-08-01

Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96 h. In vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.

The delivery of therapeutic oligonucleotides

PubMed Central

Juliano, Rudolph L.

2016-01-01

The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology. PMID:27084936

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

PubMed

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Recovery of valuable materials from spent NIMH batteries using spouted bed elutriation.

PubMed

Tanabe, Eduardo H; Schlemmer, Diego F; Aguiar, Mônica L; Dotto, Guilherme L; Bertuol, Daniel A

2016-04-15

In recent years, a great increase in the generation of spent batteries occurred. Then, efficient recycling ways and correct disposal of hazardous wastes are necessary. An alternative to recover the valuable materials from spent NiMH batteries is the spouted bed elutriation. The aim of this study was to apply the mechanical processing (grinding and sieving) followed by spouted bed elutriation to separate the valuable materials present in spent NiMH batteries. The results of the manual characterization showed that about 62 wt.% of the batteries are composed by positive and negative electrodes. After the mechanical separation processes (grinding, sieving and spouted bed elutriation), three different fractions were obtained: 24.21 wt.% of metals, 28.20 wt.% of polymers and 42.00 wt.% of powder (the positive and negative electrodes). It was demonstrated that the different materials present in the spent NiMH batteries can be efficiently separated using a simple and inexpensive mechanical processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Animal models of arrhythmogenic right ventricular cardiomyopathy: what have we learned and where do we go? Insight for therapeutics.

PubMed

Padrón-Barthe, Laura; Domínguez, Fernando; Garcia-Pavia, Pablo; Lara-Pezzi, Enrique

2017-09-01

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically-determined cardiac heart muscle disorder characterized by fibro-fatty replacement of the myocardium that results in heart failure and sudden cardiac death (SCD), predominantly in young males. The disease is often caused by mutations in genes encoding proteins of the desmosomal complex, with a significant minority caused by mutations in non-desmosomal proteins. Existing treatment options are based on SCD prevention with the implantable cardioverter defibrillator, antiarrhythmic drugs, and anti-heart failure medication. Heart transplantation may also be required and there is currently no cure. Several genetically modified animal models have been developed to characterize the disease, assess its progression, and determine the influence of potential environmental factors. These models have also been very valuable for translational therapeutic approaches, to screen new treatment options that prevent and/or reverse the disease. Here, we review the available ARVC animal models reported to date, highlighting the most important pathophysiological findings and discussing the effect of treatments tested so far in this setting. We also describe gaps in our knowledge of the disease, with the goal of stimulating research and improving patient outcomes.

Therapeutic Significance of Loligo vulgaris (Lamarck, 1798) ink Extract: A Biomedical Approach

PubMed Central

Nadarajah, Sri Kumaran; Vijayaraj, Radha; Mani, Jayaprakashvel

2017-01-01

Background: The squid ink extract is well known for its biomedical properties. Objective: In this study, squid Loligo vulgaris was collected from Tuticorin costal water, Bay of Bengal, India. Materials and Methods: Proximate composition of the crude squid ink was studied and found to have protein as the major component over lipid and carbohydrates. Further, bioactive fractions of squid ink were extracted with ethanol, and therapeutic applications such as hemolytic, antioxidant, antimicrobial, and in vitro anti-inflammatory properties were analyzed using standard methods. Results: In hemolytic assay, the squid ink extract exhibited a maximum hemolytic activity of 128 hemolytic unit against tested erythrocytes. In DPPH assay, the ethanolic extract of squid ink has exhibited an antioxidant activity of 83.5%. The squid ink was found to be potent antibacterial agent against the pathogens tested. 200 μL of L. vulgaris ink extract showed remarkable antibacterial activity as zone of inhibition against Escherichia coli (28 mm), Klebsiella pneumoniae (22 mm), Pseudomonas aeruginosa (21 mm), and Staphylococcus aureus (24 mm). The 68.9% inhibition of protein denaturation by the squid ink extract indicated that it has very good in vitro anti-inflammatory properties. The Fourier transform infrared spectroscopy analysis of the ethanolic extracts of the squid ink indicated the presence of functional groups such as 1° and 2° amines, amides, alkynes (terminal), alkenes, aldehydes, nitriles, alkanes, aliphatic amines, carboxylic acids, and alkyl halides, which complements the biochemical background of therapeutic applications. Conclusion: Hence, results of this study concluded that the ethanolic extract of L. vulgaris has many therapeutic applications such as antimicrobial, antioxidant, and anti-inflammatory activities. SUMMARY Squid ink is very high in a number of important nutrients. It’s particularly high in antioxidants for instance, which as well all know help to protect

Translational experimental therapeutics: The translation of laboratory-based discovery into disease-related therapy.

PubMed

Kieburtz, Karl; Olanow, C Warren

2007-04-01

In the past decade, there has been an increasing emphasis on laboratory-based translational research. This has led to significant scientific advances in our understanding of disease mechanisms and in the development of novel approaches to therapy such as gene therapy, RNA interference, and stem cells. However, the translation of these remarkable scientific achievements into new and effective disease-modifying therapies has lagged behind these scientific accomplishments. We use the term "translational experimental therapeutics" to describe the pathway between the discovery of a basic disease mechanism or novel therapeutic approach and its translation into an effective treatment for patients with a specific disease. In this article, we review the components of this pathway, and discuss issues that might impede this process. Only by optimizing this pathway can we realize the full therapeutic potential of current scientific discoveries and translate the astounding advances that have been accomplished in the laboratory into effective treatments for our patients. Copyright (c) 2007 Mount Sinai School of Medicine.

The role of surgery in the therapeutic approach of gastric cancer liver metastases.

PubMed

Mastoraki, Aikaterini; Benetou, Christina; Mastoraki, Sotiria; Papanikolaou, Ioannis S; Danias, Nikolaos; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

2016-09-01

Gastric cancer (GC) currently prevails as the second cause of death by malignancy worldwide. Estimations suggest that 35 % of affected patients appear with synchronous distant metastases. The vast majority of patients present with hepatic metastatic disease, sometimes accompanied by synchronous peritoneal and lung dissemination. The disease mostly remains asymptomatic at an early stage, with few reported cases of incidental abdominal discomfort. As the cancer advances, symptoms such as nausea or vomiting arise, along with indigestion and dysphagia, blood loss in the form of melena or hematemesis, as well as anorexia and weight loss. Having spread to the liver, it also causes jaundice due to hepatomegaly and general inanition. Despite recent research on the therapeutic strategies against GC metastatic disease, surgical resection appears the only potentially curative approach. Unfortunately, the majority of patients are not eligible to undergo surgical intervention. With regard to treatment modalities of the advanced stage disease, the role of metastasectomy is still debatable and quite unclear, while prolonged survival was succeeded only under certain specific circumstances. Systemic chemotherapy remains however another option, as well as local management in the form of cryotherapy, radiofrequency ablation, or transcatheter arterial chemoembolization. The aims of this review were to evaluate the results of surgical treatment for metastatic GC with special reference to the extent of its histological spread and to present the recent literature in order to provide an update on the current concepts of advanced surgical management of this entity. Relevant publications in the last two decades are briefly reviewed.

Nanobubbles: a promising efficient tool for therapeutic delivery.

PubMed

Cavalli, Roberta; Soster, Marco; Argenziano, Monica

2016-01-01

In recent decades ultrasound-guided delivery of drugs loaded on nanocarriers has been the focus of increasing attention to improve therapeutic treatments. Ultrasound has often been used in combination with microbubbles, micron-sized spherical gas-filled structures stabilized by a shell, to amplify the biophysical effects of the ultrasonic field. Nanometer size bubbles are defined nanobubbles. They were designed to obtain more efficient drug delivery systems. Indeed, their small sizes allow extravasation from blood vessels into surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Additionally, nanobubbles might be endowed with improved stability and longer residence time in systemic circulation. This review will describe the physico-chemical properties of nanobubbles, the formulation parameters and the drug loading approaches, besides potential applications as a therapeutic tool.

Therapeutic applications of carbon nanotubes: opportunities and challenges.

PubMed

Rogers-Nieman, Gabrielle M; Dinu, Cerasela Zoica

2014-01-01

Based on their physicochemical properties that allow efficient functionalization with biomolecules and cellular membrane translocation, as well as on their applications in Raman and near-infrared fluorescence imaging, carbon nanotubes (CNTs) have been proposed as viable candidates for developing therapeutic platforms that ensure targeting of tumor cells without affecting healthy cells. This article reviews the research on toxicological effects of CNTs on host cells, as well as their pharmacological profiles on cancer cells. The potential impact of this approach is discussed along with some potential pitfalls that will need to be overcome when therapeutic implementation CNTs are considered. For further resources related to this article, please visit the WIREs website. The authors declare no competing financial interest. © 2014 Wiley Periodicals, Inc.

Work-Life and Well-Being in U.K. Therapeutic Prison Officers: A Thematic Analysis.

PubMed

Walker, Emma J; Egan, Helen H; Jackson, Craig A; Tonkin, Matthew

2018-06-01

Previous research has clearly demonstrated the positive impact of therapeutic interventions on offenders' well-being. Much less is known about the impact on prison staff facilitating and delivering such interventions. We employed qualitative methodology to capture a deeper understanding of the work of therapeutic prison officers. Seven prison officers working in a U.K. Category B therapeutic community prison were interviewed about their working lives, including their own participation in therapy. Following a thematic analysis approach, key findings indicated that the physical and cultural work environment was very important to staff; the therapeutic element of their job role, although demanding, was both satisfying and rewarding; and that working in a therapeutic prison environment provided the opportunity for personal as well as professional development. We conclude that further attention should be given to the unique nature of therapeutic prison work and the positive impact it can have on well-being at work.

Clinical development of CT-P10 and other biosimilar cancer therapeutics.

PubMed

Kim, Won Seog; Coiffier, Bertrand; Kwon, Hyuk-Chan; Kim, SuYeon

2017-05-01

Biosimilars are highly similar versions of approved biologic drugs that may confer equivalent efficacy at a reduced cost. Patents for several biological cancer therapeutics are past or approaching expiry, presenting an opportunity to increase affordability and global accessibility of key drugs through the development of biosimilars. To receive approval, a biosimilar must show no clinically meaningful differences from the reference product in terms of efficacy or safety. The first monoclonal antibody biosimilar cancer therapeutic to gain approval was CT-P10, a biosimilar of rituximab. Here, we review the oncology clinical development program for CT-P10, providing insights into the rationale for, and design of, CT-P10 clinical trials in patients with cancer. Trials of biosimilar cancer therapeutics in development are also discussed.

Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

PubMed Central

Nguyen, Minh Khanh; Alsberg, Eben

2014-01-01

Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years. PMID:25242831

Therapeutic polymers for dental adhesives: Loading resins with bio-active components

PubMed Central

Imazato, Satoshi; Ma, Sai; Chen, Ji-hua; Xu, Hockin H.K.

2014-01-01

Objectives Many recent adhesives on the market exhibit reasonable clinical performance. Future innovations in adhesive materials should therefore seek out novel properties rather than simply modifying existing technologies. It is proposed that adhesive materials that are “bio-active” could contribute to better prognosis of restorative treatments. Methods This review examines the recent approaches used to achieve therapeutic polymers for dental adhesives by incorporating bio-active components. A strategy to maintain adhesive restorations is the focus of this paper. Results Major trials on therapeutic dental adhesives have looked at adding antibacterial activities or remineralization effects. Applications of antibacterial resin monomers based on quaternary ammonium compounds have received much research attention, and the loading of nano-sized bioactive particles or multiple ion-releasing glass fillers have been perceived as advantageous since they are not expected to influence the mechanical properties of the carrier polymer. Significance The therapeutic polymer approaches described here have the potential to provide clinical benefits. However, not many technological applications in this category have been successfully commercialized. Clinical evidence as well as further advancement of these technologies can be a driving force to make these new types of materials clinically available. PMID:23899387

S100-alarmins: potential therapeutic targets for arthritis.

PubMed

Austermann, Judith; Zenker, Stefanie; Roth, Johannes

2017-07-01

In arthritis, inflammatory processes are triggered by numerous factors that are released from joint tissues, promoting joint destruction and pathological progression. During inflammation, a novel family of pro-inflammatory molecules called alarmins is released, amplifying inflammation and joint damage. Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the pathogenesis of arthritis, recent advances and the future prospects in terms of therapeutic implications are considered. Expert opinion: There is still an urgent need for novel treatment strategies addressing the local mechanisms of joint inflammation and tissue destruction, offering promising therapeutic alternatives. S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are endogenous triggers of inflammation, defining these proteins as promising targets for local suppression of arthritis. In murine models, the blockade of S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there are several lines of evidence that S100-alarmins may already be targeted in therapeutic approaches in man.

Automated DBS microsampling, microscale automation and microflow LC-MS for therapeutic protein PK.

PubMed

Zhang, Qian; Tomazela, Daniela; Vasicek, Lisa A; Spellman, Daniel S; Beaumont, Maribel; Shyong, BaoJen; Kenny, Jacqueline; Fauty, Scott; Fillgrove, Kerry; Harrelson, Jane; Bateman, Kevin P

2016-04-01

Reduce animal usage for discovery-stage PK studies for biologics programs using microsampling-based approaches and microscale LC-MS. We report the development of an automated DBS-based serial microsampling approach for studying the PK of therapeutic proteins in mice. Automated sample preparation and microflow LC-MS were used to enable assay miniaturization and improve overall assay throughput. Serial sampling of mice was possible over the full 21-day study period with the first six time points over 24 h being collected using automated DBS sample collection. Overall, this approach demonstrated comparable data to a previous study using single mice per time point liquid samples while reducing animal and compound requirements by 14-fold. Reduction in animals and drug material is enabled by the use of automated serial DBS microsampling for mice studies in discovery-stage studies of protein therapeutics.

Intestinal ischemia-reperfusion injury in horses: pathogenesis and therapeutics.

PubMed

Wong, David M; Moore, Rustin M; Brockus, Charles W

2012-08-01

This article discusses the potential role of oxidative injury to the intestinal tract of horses and the therapeutic approaches that have been investigated to decrease cellular damage secondary to ischemia-reperfusion (IR) injury. Equine colic is a major concern for horse owners and veterinary practitioners. Strangulating and obstructive lesions of the small and large intestines commonly require intervention in patients via exploratory celiotomy. However, the application of information from experimentally induced IR injury in horses to clinical cases of naturally occurring equine colic is not clear. Thus, while the exact mechanisms and clinical significance of intestinal IR are being defined and may be matters of academic debate, a review of the available information may provide knowledge of potential underlying pathophysiologic mechanisms contributing to intestinal injury in equine colic. This information may allow clinicians to offer additional therapeutic strategies for horses with strangulating obstruction of the small or large intestine. Further clinical study of the therapeutic options for horses with naturally occurring disease is warranted.

Frondoside A potentiates the effects of conventional therapeutic agents in acute leukemia.

PubMed

Sajwani, F H; Collin, P; Adrian, T E

2017-12-01

Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy. This study is the first comparing the efficacy of frondoside A to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of vincristine sulphate, asparaginase and prednisolone alone and in combination with frondoside A. The inhibitory concentration 50 (IC 50 ) for each compound was determined for the cell lines. CCRF-CEM cells were very sensitive to frondoside A treatment while HL-60 and THP1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs. Synergistic effects were seen with most of the combinations. Frondoside A may be valuable in the treatment of acute leukemia, particularly when used in combination with current therapeutic drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal Tumor Organoids

NASA Astrophysics Data System (ADS)

Liu, Xin; Flinders, Colin; Mumenthaler, Shannon M.; Hummon, Amanda B.

2018-03-01

Patient-derived colorectal tumor organoids (CTOs) closely recapitulate the complex morphological, phenotypic, and genetic features observed in in vivo tumors. Therefore, evaluation of drug distribution and metabolism in this model system can provide valuable information to predict the clinical outcome of a therapeutic response in individual patients. In this report, we applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to examine the spatial distribution of the drug irinotecan and its metabolites in CTOs from two patients. Irinotecan is a prodrug and is often prescribed as part of therapeutic regimes for patients with advanced colorectal cancer. Irinotecan shows a time-dependent and concentration-dependent permeability and metabolism in the CTOs. More interestingly, the active metabolite SN-38 does not co-localize well with the parent drug irinotecan and the inactive metabolite SN-38G. The phenotypic effect of irinotecan metabolism was also confirmed by a viability study showing significantly reduced proliferation in the drug treated CTOs. MALDI-MSI can be used to investigate various pharmaceutical compounds in CTOs derived from different patients. By analyzing multiple CTOs from a patient, this method could be used to predict patient-specific drug responses and help to improve personalized dosing regimens. [Figure not available: see fulltext.

Design of therapeutic vaccines as a novel antibody therapy for cardiovascular diseases.

PubMed

Nakagami, Hironori

2017-09-01

Vaccines are primarily used worldwide as a preventive medicine for infectious diseases and have recently been applied to cancer. We and others have developed therapeutic vaccines designed for cardiovascular diseases that are notably different from previous vaccines. In the case of cancer vaccines, a specific protein in cancer cells is a target antigen, and the activation of cytotoxic T cells (CTL) is required to kill and remove the antigen-presenting cancer cells. Our therapeutic vaccines work against hypertension by targeting angiotensin II (Ang II) as the antigen, which is an endogenous hormone. Therapeutic vaccines must avoid CTL activation and induce the blocking antibodies for Ang II. The goal of our therapeutic vaccine for cardiovascular diseases is to induce the specific antibody response toward the target protein without inducing T-cell or antibody-mediated inflammation through the careful selection of the target antigen, carrier protein and adjuvants. The goal of our therapeutic vaccine is similar to that of antibody therapy. Recently, multiple antibody-based drugs have been developed for cancer, immune-related diseases, and dyslipidemia, which are efficient but expensive. If the effect of a therapeutic vaccine is nearly equivalent to antibody therapy as an alternative approach, the lower medical cost and improvement in drug adherence can be advantages of therapeutic vaccines. In this review, we will describe our concept of therapeutic vaccines for cardiovascular diseases and the future directions of therapeutic vaccines as novel antibody therapies. Copyright © 2017. Published by Elsevier Ltd.

Novel therapeutic agents for osteosarcoma.

PubMed

O'Day, Kathleen; Gorlick, Richard

2009-04-01

Osteosarcoma is the most common malignant primary bone tumor in childhood. Despite multiagent chemotherapy and aggressive surgical resection, 30% of patients with localized disease and 80% of patients with metastatic disease at diagnosis will relapse. Survival for these patients has remained unchanged over the past 20 years. A number of novel agents in various stages of development hold promise for improving therapy for patients with osteosarcoma. This article will focus on novel therapeutic approaches, including agents targeting signal-transduction pathways, inhibitors of the tumor microenvironment and immunomodulatory agents, as well as overcoming resistance mechanisms and the use of novel delivery mechanisms.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

PubMed Central

Gimona, Mario; Pachler, Karin; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva

2017-01-01

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path. PMID:28587212

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.

PubMed

Gimona, Mario; Pachler, Karin; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva

2017-06-03

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

Recent developments in protein and peptide parenteral delivery approaches

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K

2014-01-01

Discovery of insulin in the early 1900s initiated the research and development to improve the means of therapeutic protein delivery in patients. In the past decade, great emphasis has been placed on bringing protein and peptide therapeutics to market. Despite tremendous efforts, parenteral delivery still remains the major mode of administration for protein and peptide therapeutics. Other routes such as oral, nasal, pulmonary and buccal are considered more opportunistic rather than routine application. Improving biological half-life, stability and therapeutic efficacy is central to protein and peptide delivery. Several approaches have been tried in the past to improve protein and peptide in vitro/in vivo stability and performance. Approaches may be broadly categorized as chemical modification and colloidal delivery systems. In this review we have discussed various chemical approaches such as PEGylation, hyperglycosylation, mannosylation, and colloidal carriers including microparticles, nanoparticles, liposomes, carbon nanotubes and micelles for improving protein and peptide delivery. Recent developments on in situ thermosensitive gel-based protein and peptide delivery have also been described. This review summarizes recent developments on some currently existing approaches to improve stability, bioavailability and bioactivity of peptide and protein therapeutics following parenteral administration. PMID:24592957

Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

PubMed

Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

2016-06-01

Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Therapeutic conversation to improve mood in nursing home residents with Alzheimer's disease.

PubMed

Tappen, Ruth M; Williams, Christine L

2009-10-01

Few studies have tested strategies to address the mental health needs of individuals with Alzheimer's disease (AD). To test a newly developed, empirically based modified counseling approach, 30 nursing home residents with AD were randomly assigned to a modified counseling (Therapeutic Conversation) treatment group or usual care control group. Mini-Mental State Examination mean scores were 10.60 (SD = 6.99) for the treatment group and 12.26 (SD = 7.43) for the control group. Individual treatment was provided three times per week for 16 weeks. On the posttest, treatment group participants evidenced significantly less negative mood than the control group on the Montgomery-Asberg Depression Rating Scale and the Sadness and Apathy subscales of the Alzheimer's Disease and Related Disorders Mood Scale. The differences approached significance on the Dementia Mood Assessment Scale. Results suggest that a therapeutic counseling approach can be effective in treating the dysphoria commonly found in individuals with AD. Copyright 2009, SLACK Incorporated.