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Sample records for antioxidant therapeutic advances

  1. Molecular hydrogen: a therapeutic antioxidant and beyond

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2016-01-01

    Full Text Available Molecular hydrogen (H2 medicine research has flourished since a landmark publication in Nature Medicine that revealed the antioxidant and cytoprotective effects of hydrogen gas in a focal stroke model. Emerging evidence has consistently demonstrated that molecular hydrogen is a promising therapeutic option for a variety of diseases and the underlying comprehensive mechanisms is beyond pure hydroxyl radicals scavenging. The non-toxicity at high concentrations and rapid cellular diffusion features of molecular hydrogen ensure the feasibility and readiness of its clinical translation to human patients.

  2. Therapeutic advances in muscular dystrophy

    OpenAIRE

    Leung, Doris G; Wagner, Kathryn R

    2013-01-01

    The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystr...

  3. Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

    Science.gov (United States)

    2015-01-01

    Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574

  4. Advancements in therapeutically-targeting orphan GPCRs

    Directory of Open Access Journals (Sweden)

    Jennifer eStockert

    2015-05-01

    Full Text Available G-protein coupled receptors (GPCRs are popular biological targets for drug discovery and development. To date there are more than 140 orphan GPCRs, i.e. receptors whose endogenous ligands are unknown. Traditionally orphan GPCRs have been difficult to study and the development of therapeutic compounds targeting these receptors has been extremely slow although these GPCRs are considered important targets based on their distribution and behavioral phenotype revealed by animals lacking the receptor. Recent advances in several methods used to study orphan receptors, including protein crystallography and homology modeling are likely to be useful in the identification of therapeutics targeting these receptors. In the past 13 years, over a dozen different Class A GPCRs have been crystallized; this trend is exciting, since homology modeling of GPCRs has previously been limited by the availability of solved structures. As the number of solved GPCR structures continues to grow so does the number of templates that can be used to generate increasingly accurate models of phylogenetically-related orphan GPCRs. The availability of solved structures along with the advances in using multiple templates to build models (in combination with molecular dynamics simulations that reveal structural information not provided by crystallographic data and methods for modeling hard-to-predict flexible loop regions have improved the quality of GPCR homology models. This, in turn, has improved the success rates of virtual ligand screens that use homology models to identify potential receptor binding compounds. Experimental testing of the predicted hits and validation using traditional GPCR pharmacological approaches can be used to drive ligand-based efforts to probe orphan receptor biology as well as to define the chemotypes and chemical scaffolds important for binding. As a result of these advances, orphan GPCRs are emerging from relative obscurity as a new class of drug

  5. The antioxidant paradox: what are antioxidants and how should they be used in a therapeutic context for cancer.

    Science.gov (United States)

    Bonner, Michael Y; Arbiser, Jack L

    2014-01-01

    So-called antioxidants have yet to make a clinical impact on the treatment of human cancer. The reasons for this failure are several. First, many agents that are called antioxidants are truly antioxidants at a given dose, but this dose may not have been given in clinical trials. Second, many agents are not antioxidants at all. Third, not all tumors use reactive oxygen as a signaling mechanism. Finally, reactive oxygen inhibition is often insufficient to kill or regress a tumor cell by itself, but requires sequential introduction of a therapeutic agent for maximal effect. We hope to provide a framework for the logical use of these agents in cancer.

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

    African Journals Online (AJOL)

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

  7. Significance of antioxidant potential of plants and its relevance to therapeutic applications.

    Science.gov (United States)

    Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong

    2015-01-01

    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

  8. Recent therapeutic advances in chronic lymphocytic leukemia

    Science.gov (United States)

    Bose, Prithviraj; Gandhi, Varsha

    2017-01-01

    The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs. Thus, successful therapeutic targeting of the B-cell receptor signaling pathway and of the Bcl-2 anti-apoptotic protein with small molecules has now made chemotherapy-free approaches possible, hopefully mitigating the risk of development of therapy-related myeloid neoplasms and making eventual cure of CLL with the use of optimal drug combinations a realistic goal. Most importantly, these therapies have demonstrated unprecedented efficacy in patients with deletion 17p/TP53 mutation, a subset that historically has been very difficult to treat. However, as we gain more experience with the newer agents, unique safety concerns and resistance mechanisms have emerged, as has the issue of cost, as these expensive drugs are currently administered indefinitely. Accordingly, novel laboratory-based strategies and clinical trial designs are being explored to address these issues. The availability of whole exome/genome sequencing has given us profound insights into the mutational landscape of CLL. In this article, we highlight some of the most impactful advances since this topic was last reviewed in this journal. PMID:29152232

  9. [Therapeutic advances in cystic fibrosis in 2014].

    Science.gov (United States)

    Durupt, S; Mazur, S; Reix, P

    2016-02-01

    Twenty-five years after the cystic fibrosis (CF) gene identification, this discovery actually begins to benefit to patients. Increasing our knowledge on CFTR biology, as well as technical progress made in order to screen for new drugs have made therapeutic strategies move an important step forward. It is likely that in the forthcoming years, the panel of molecules available for CF patients will be larger, with new activators and potentiators. The disease by itself may consequently change in its natural history. CF is an example of the so-called personalized medicine, aiming to fit treatment according to patient's genetic background. Ongoing clinical trials may enlarge the actually limited eligible number of CF patients for new drugs such as ivacaftor. Beyond this exciting and promising new therapeutic approach, one may not push symptomatic treatments on the side. Improvements have been made for inhaled antibiotics administration, aiming to simplify patient's life; clinical trials using new molecules able to liquefy mucus or with anti-inflammatory properties are actually underway. One important next step in the care for CF will be to design and conduct early intervention trials in CF infants. Newborn screening program have been widely implanted around the word, and cohorts studies have shown that both functional and structural abnormalities occurred very early, making the therapeutic window of opportunity tight. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Advances in spinal muscular atrophy therapeutics.

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    Parente, Valeria; Corti, Stefania

    2018-01-01

    Spinal muscular atrophy (SMA) is a progressive, recessively inherited neuromuscular disease, characterized by the degeneration of lower motor neurons in the spinal cord and brainstem, which leads to weakness and muscle atrophy. SMA currently represents the most common genetic cause of infant death. SMA is caused by the lack of survival motor neuron (SMN) protein due to mutations, which are often deletions, in the SMN1 gene. In the absence of treatments able to modify the disease course, a considerable burden falls on patients and their families. Greater knowledge of the molecular basis of SMA pathogenesis has fuelled the development of potential therapeutic approaches, which are illustrated here. Nusinersen, a modified antisense oligonucleotide that modulates the splicing of the SMN2 mRNA transcript, is the first approved drug for all types of SMA. Moreover, the first gene therapy clinical trial using adeno-associated virus (AAV) vectors encoding SMN reported positive results in survival and motor milestones achievement. In addition, other strategies are in the pipeline, including modulation of SMN2 transcripts, neuroprotection, and targeting an increasing number of other peripheral targets, including the skeletal muscle. Based on this premise, it is reasonable to expect that therapeutic approaches aimed at treating SMA will soon be changed, and improved, in a meaningful way. We discuss the challenges with regard to the development of novel treatments for patients with SMA, and depict the current and future scenarios as the field enters into a new era of promising effective treatments.

  11. Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

    Science.gov (United States)

    Molina, Víctor M.; Carrasco, Rodrigo A.; Figueroa, Elías; Letelier, Pablo; Castillo, Rodrigo L.

    2017-01-01

    Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs. PMID:28862654

  12. Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jorge G. Farías

    2017-09-01

    Full Text Available Oxidative stress (OS refers to the imbalance between the generation of reactive oxygen species (ROS and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs.

  13. Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

    Science.gov (United States)

    Hackenhaar, Fernanda S.; Medeiros, Tássia M.; Heemann, Fernanda M.; Behling, Camile S.; Putti, Jordana S.; Mahl, Camila D.; Verona, Cleber; da Silva, Ana Carolina A.; Guerra, Maria C.; Gonçalves, Carlos A. S.; Oliveira, Vanessa M.; Riveiro, Diego F. M.; Vieira, Silvia R. R.

    2017-01-01

    After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients. PMID:28553435

  14. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles

    Directory of Open Access Journals (Sweden)

    Jingga Morry

    2017-04-01

    Full Text Available Oxidative stress, mainly contributed by reactive oxygen species (ROS, has been implicated in pathogenesis of several diseases. We review two primary examples; fibrosis and cancer. In fibrosis, ROS promote activation and proliferation of fibroblasts and myofibroblasts, activating TGF-β pathway in an autocrine manner. In cancer, ROS account for its genomic instability, resistance to apoptosis, proliferation, and angiogenesis. Importantly, ROS trigger cancer cell invasion through invadopodia formation as well as extravasation into a distant metastasis site. Use of antioxidant supplements, enzymes, and inhibitors for ROS-generating NADPH oxidases (NOX is a logical therapeutic intervention for fibrosis and cancer. We review such attempts, progress, and challenges. Lastly, we review how nanoparticles with inherent antioxidant activity can also be a promising therapeutic option, considering their additional feature as a delivery platform for drugs, genes, and imaging agents.

  15. Antioxidant Potential of a Polyherbal Antimalarial as an Indicator of Its Therapeutic Value

    Directory of Open Access Journals (Sweden)

    Protus Arrey Tarkang

    2013-01-01

    Full Text Available Nefang is a polyherbal product composed of Mangifera indica (bark and leaf, Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves, used for the treatment of malaria. Compounds with antioxidant activity are believed to modulate plasmodial infection. Antioxidant activity of the constituent aqueous plants extracts, in vitro, was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH, total phenolic content (TPC, and ferric reducing antioxidant power (FRAP methods and, in vivo, Nefang (100 and 500 mg kg−1 activity was evaluated in carbon tetrachloride-induced oxidative stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid peroxidation by the malondialdehyde and total proteins assays were carried out. P. guajava, M. indica leaf, and bark extracts had the highest antioxidant properties in all three assays, with no statistically significant difference. Rats treated with the carbon tetrachloride had a statistically significant decrease in levels of triglycerides, superoxide dismutase, and catalase (P<0.05 and increase in malondialdehyde activity, total protein levels, and liver and renal function markers, whereas rats treated with Nefang showed increased levels in the former and dose-dependent decrease towards normal levels in the later. These results reveal the constituent plants of Nefang that contribute to its in vivo antioxidant potential. This activity is a good indication of the therapeutic potential of Nefang.

  16. [Decrease in toxicity and therapeutic effect of zoledronic acid in combination therapy with different antioxidant extracts].

    Science.gov (United States)

    Lopez-Morata, José Antonio; Olivares, Amparo; Alcaraz, Miguel

    Zoledronic acid is used in the treatment of cancer-related diseases, although its use has been associated with avascular osteonecrosis. To determine the possible protective effect of a range of antioxidant substances against the inhibition of human prostate epithelial cell growth (PNT2) and transgenic adenocarcinoma mouse prostate tumour cells (TRAMP-C1), in treatments combining zoledronic acid and ionising radiation (IR). Cell survival is studied via cell viability assays (MTT) for 2 cell lines in isolated and combined treatments with zoledronic acid and/or IR, as well as the effect of adding 3 antioxidant substances. Zoledronic acid displays a significant cytotoxic effect over PNT2 and TRAMP-C1 cells (P<.001). The administration of antioxidants together with the zoledronic acid shows a protective effect for normal prostate cells, yet not so for prostate tumour cells. However, the administration of rosmarinic acid and apigenin in treatments combined with zoledronic acid provides a protective effect from the harmful effects of applying ionizing radiation, not only for normal PNT2 cells, but also for tumour cells. The use of antioxidant substances decreases the cytotoxic effect of zoledronic acid over non-tumour cells, and as such could be used in benign diseases. Furthermore, in the combined treatment using ionising radiation, these antioxidants also produced a protective effect in tumour cells, thus reducing the therapeutic effect sought by combining the treatment with radiation. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Advances in sarcoma gene mutations and therapeutic targets.

    Science.gov (United States)

    Gao, Peng; Seebacher, Nicole A; Hornicek, Francis; Guo, Zheng; Duan, Zhenfeng

    2018-01-01

    Sarcomas are rare and complex malignancies that have been associated with a poor prognostic outcome. Over the last few decades, traditional treatment with surgery and/or chemotherapy has not significantly improved outcomes for most types of sarcomas. In recent years, there have been significant advances in the understanding of specific gene mutations that are important in driving the pathogenesis and progression of sarcomas. Identification of these new gene mutations, using next-generation sequencing and advanced molecular techniques, has revealed a range of potential therapeutic targets. This, in turn, may lead to the development of novel agents targeted to different sarcoma subtypes. In this review, we highlight the advances made in identifying sarcoma gene mutations, including those of p53, RB, PI3K and IDH genes, as well as novel therapeutic strategies aimed at utilizing these mutant genes. In addition, we discuss a number of preclinical studies and ongoing early clinical trials in sarcoma targeting therapies, as well as gene editing technology, which may provide a better choice for sarcoma patient management. Published by Elsevier Ltd.

  18. Advances in the Analytical Methods for Determining the Antioxidant ...

    African Journals Online (AJOL)

    Free radicals and reactive oxygen species (ROS) have been implicated in contributing to the processes of aging and disease. In an effort to combat free radical activity, scientists are studying the effects of increasing individuals' antioxidant levels through diet and dietary supplements. Honey appears to act as an antioxidant ...

  19. Recent Advances in Therapeutic Genome Editing in China.

    Science.gov (United States)

    Yang, Yang; Wang, Qingnan; Li, Qian; Men, Ke; He, Zhiyao; Deng, Hongxin; Ji, Weizhi; Wei, Yuquan

    2018-02-01

    Editing of the genome to correct disease-causing mutations is a promising approach for the treatment of human diseases. Recent advances in the development of programmable nuclease-based genome editing tools have substantially improved the ability to make precise changes in the human genome. Genome editing technologies are already being used to correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional gene therapies. Chinese scientists have made remarkable breakthroughs in the field of therapeutic genome editing, particularly with the first clinical trial involving the clustered regularly interspaced short palindromic repeats-caspase 9 system that began in China. Herein, current progress toward developing programmable nuclease-based gene therapies is introduced, as well as future prospects and challenges in China.

  20. Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives

    Directory of Open Access Journals (Sweden)

    Alexander V. Maksimenko

    2016-01-01

    Full Text Available Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with O2∙- superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO.

  1. Recent advancement of therapeutic endoscopy in the esophageal benign diseases

    Science.gov (United States)

    Bechara, Robert; Inoue, Haruhiro

    2015-01-01

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  2. Emerging therapeutics for advanced thyroid malignancies: rationale and targeted approaches.

    Science.gov (United States)

    Harris, Pamela Jo; Bible, Keith C

    2011-10-01

    Thyroid cancer is an emerging public health concern. In the USA, its incidence has doubled in the past decade, making it the eighth 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. 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. 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.

  3. Therapeutic orchids: traditional uses and recent advances--an overview.

    Science.gov (United States)

    Hossain, Mohammad Musharof

    2011-03-01

    Orchids have been used as a source of medicine for millennia to treat different diseases and ailments including tuberculosis, paralysis, stomach disorders, chest pain, arthritis, syphilis, jaundice, cholera, acidity, eczema, tumour, piles, boils, inflammations, menstrual disorder, spermatorrhea, leucoderma, diahorrhea, muscular pain, blood dysentery, hepatitis, dyspepsia, bone fractures, rheumatism, asthma, malaria, earache, sexually transmitted diseases, wounds and sores. Besides, many orchidaceous preparations are used as emetic, purgative, aphrodisiac, vermifuge, bronchodilator, sex stimulator, contraceptive, cooling agent and remedies in scorpion sting and snake bite. Some of the preparations are supposed to have miraculous curative properties but rare scientific demonstration available which is a primary requirement for clinical implementations. Incredible diversity, high alkaloids and glycosides content, research on orchids is full of potential. Meanwhile, some novel compounds and drugs, both in phytochemical and pharmacological point of view have been reported from orchids. Linking of the indigenous knowledge to the modern research activities will help to discover new drugs much more effective than contemporary synthetic medicines. The present study reviews the traditional therapeutic uses of orchids with its recent advances in pharmacological investigations that would be a useful reference for plant drug researches, especially in orchids. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    Directory of Open Access Journals (Sweden)

    P. Hemachandra Reddy

    2011-02-01

    Full Text Available Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma.

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

    Directory of Open Access Journals (Sweden)

    Tereza eCindrova-Davies

    2014-05-01

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

  6. Antioxidants

    Science.gov (United States)

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

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

    Science.gov (United States)

    2015-10-01

    as an oral contraceptive [6, 7]. Recently, its anti- cancer activity has been reported against advanced breast cancer [8] and head and neck squamous...Award Number: W81XWH-141-0154 TITLE: “A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment” PRINCIPAL INVESTIGATOR...Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment” 5a. CONTRACT NUMBER: 5b. GRANT NUMBER: W81XWH-14-1-0154 5c. PROGRAM ELEMENT

  8. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges

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    Vugmeyster, Yulia; Xu, Xin; Theil, Frank-Peter; Khawli, Leslie A; Leach, Michael W

    2012-01-01

    Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which would ultimately lead to a higher success rate in drug development. In toxicology, it is known, in general, what studies are needed to safely develop therapeutic proteins, and what studies do not provide relevant information. One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity. In this review, we will highlight the emerging science and technology, as well as the challenges around the pharmacokinetic- and safety-related issues in drug development of mAbs and other therapeutic proteins. PMID:22558487

  9. Binge-eating disorder: Clinical and therapeutic advances.

    Science.gov (United States)

    Hutson, Peter H; Balodis, Iris M; Potenza, Marc N

    2018-02-01

    Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology and pharmacology, drawing from clinical therapeutic, neuroimaging, cognitive, human genetic and animal model studies. These studies, which are still in their infancy, indicate that while there are many gaps in our knowledge, several key neural substrates appear to underpin binge-eating and may be conserved between human and animals. This observation suggests that behavioral intermediate phenotypes or endophenotypes relevant to BED may be modeled in animals, facilitating the identification and testing of novel pharmacological targets. The development of novel, safe and effective pharmacological therapies for the treatment of BED will enhance the ability of clinicians to provide optimal care for people with BED. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Drug trafficking: recent advances in therapeutics and disease.

    Science.gov (United States)

    Sprowl, J A; Sparreboom, A

    2012-11-01

    Drug transporter proteins are of ever-increasing interest because of their role both in processes regulating pharmacokinetic properties of drugs (absorption, distribution, and elimination) and in the development of cellular drug resistance through decreased uptake or increased efflux of drugs in the target organ or tumor. Further understanding of the role of transporters in drug-drug interactions and identification of these proteins as possible therapeutic targets could contribute to improved treatment of a wide variety of diseases.

  11. Advanced Development of Antiviral Prophylactics and Therapeutics (ADAPT) - Research Area 10

    Science.gov (United States)

    2014-11-17

    designing lead series analogs to optimize antiviral activity, Prosetta has initiated design of analogs based on the structural properties believed or...1-Mar-2011 - 31-May-2014 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Final Rep01i: Advanced Development of Antiviral Prophylactics and Therapeutics...Number of Papers published in non peer-reviewed journals: Final Report: Advanced Development of Antiviral Prophylactics and Therapeutics (ADAPT

  12. Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways

    Science.gov (United States)

    Aldebasi, Yousef H; Aly, Salah M; Rahmani, Arshad H

    2013-01-01

    Diabetic Retinopathy (DR) is one of the most common complications of diabetes mellitus that affects the blood vessels of the retina, leading to blindness. The current approach of treatment based on anti-inflammatory, anti-angiogenesis drugs and laser photocoagulation are effective but also shows adverse affect in retinal tissues and that can even worsen the visual abilities. Thus, a safe and effective mode of treatment is needed to control or delaying the DR. Based on the earlier evidence of the potentiality of natural products as anti-oxidants, anti-diabetic and antitumor, medicinal plants may constitute a good therapeutic approach in the prevention of DR. Curcumin, constituents of dietary spice turmeric, has been observed to have therapeutic potential in the inhibition or slow down progression of DR. In this review, we summarize the therapeutic potentiality of curcumin in the delaying the DR through antioxidant, anti-inflammatory, inhibition of Vascular Endothelial Growth and nuclear transcription factors. The strength of involvement of curcumin in the modulation of genes action creates a strong optimism towards novel therapeutic strategy of diabetic retinopathy and important mainstay in the management of diabetes and its complications DR. PMID:24379904

  13. [Recent biological and therapeutic advances in multiple myeloma].

    Science.gov (United States)

    Coppetelli, U; Avvisati, G; Tribalto, M; Cantonetti, M; La Verde, G; Petrucci, T; Stasi, R; Papa, G

    1992-09-01

    Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease.

  14. PIM kinases as therapeutic targets against advanced melanoma

    Science.gov (United States)

    Shannan, Batool; Watters, Andrea; Chen, Quan; Mollin, Stefan; Dörr, Markus; Meggers, Eric; Xu, Xiaowei; Gimotty, Phyllis A.; Perego, Michela; Li, Ling; Benci, Joseph; Krepler, Clemens; Brafford, Patricia; Zhang, Jie; Wei, Zhi; Zhang, Gao; Liu, Qin; Yin, Xiangfan; Nathanson, Katherine L.; Herlyn, Meenhard; Vultur, Adina

    2016-01-01

    Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models. Assessment of tumor tissue from melanoma patients showed that PIM kinases are expressed in pre- and post-treatment tumors, suggesting PIM kinases as promising targets in the clinic. Using knockdown studies, we showed that PIM1 contributes to melanoma cell proliferation and tumor growth in vivo; however, the presence of PIM2 and PIM3 could also influence the outcome. The inhibition of all PIM isoforms using SGI-1776 (a clinically-available PIM inhibitor) reduced melanoma proliferation and survival in preclinical models of melanoma. This was potentiated in the presence of the BRAF inhibitor PLX4720 and in the presence of PI3K inhibitors. Our findings suggest that PIM inhibitors provide promising additions to the targeted therapies available to melanoma patients. PMID:27448973

  15. Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.

    Science.gov (United States)

    Chen, Qianwei; Feng, Zhou; Tan, Qiang; Guo, Jing; Tang, Jun; Tan, Liang; Feng, Hua; Chen, Zhi

    2017-04-15

    Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Advanced functional polymers for regenerative and therapeutic dentistry.

    Science.gov (United States)

    Lai, W-F; Oka, K; Jung, H-S

    2015-07-01

    Use of ceramics and polymers continues to dominate clinical procedures in modern dentistry. Polymers have provided the basis for adhesives, tissue void fillers, and artificial replacements for whole teeth. They have been remarkably effective in the clinic at restoration of major dental functions after damage or loss of teeth. With the rapid development of polymer science, dental materials science has significantly lagged behind in harnessing these advanced polymer products. What they offer is new and unique properties superior to traditional polymers and crucially a range of properties that more closely match natural biomaterials. Therefore, we should pursue more vigorously the benefits of advanced polymers in dentistry. In this review, we highlight how the latest generation of advanced polymers will enhance the application of materials in the dental clinic using numerous promising examples. Polymers have a broad range of applications in modern dentistry. Some major applications are to construct frameworks that mimic the precise structure of tissues, to restore tooth organ function, and to deliver bioactive agents to influence cell behavior from the inside. The future of polymers in dentistry must include all these new enhancements to increase biological and clinical effectiveness beyond what can be achieved with traditional biomaterials. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Advances in therapeutic CRISPR/Cas9 genome editing.

    Science.gov (United States)

    Savić, Nataša; Schwank, Gerald

    2016-02-01

    Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Anti-oxidant and anti-microbial properties of some ethno-therapeutically important medicinal plants of Indian Himalayan Region.

    Science.gov (United States)

    Rawat, Sandeep; Jugran, Arun K; Bahukhandi, Amit; Bahuguna, Asutosh; Bhatt, Indra D; Rawal, Ranbeer S; Dhar, Uppeandra

    2016-12-01

    Therapeutic potential of medicinal plants as a source of noble natural anti-oxidants and anti-microbial agents has been well recognised all across the globe. In this study, phenolic compounds, in vitro anti-oxidant activity and anti-microbial properties have been investigated in five Himalayan medicinal plants, (e.g., Acorus calamus, Habenaria intermedia, Hedychium spicatum, Roscoea procera and Valeriana jatamansi) in different solvent systems. R. procera exhibited significantly (p anti-oxidant activity. Also, R. procera and H. spicatum were found rich in gallic acid; V. jatamansi in catechin, hydroxylbenzoic acid and caffeic acid and H. intermedia in hydroxyl benzoic acid. Solvent systems showed species specific response for extraction of total flavonoids and anti-oxidant activity. All the extracts were found effective against different bacterial and fungal strains in a dose dependent manner and maximum antimicrobial activity was found in R. procera as compared to other species. All the plant extracts showed greater activity against bacterial strains as compared to fungal strains. The results of this study suggest that extract of these species can be used as natural anti-oxidant to reduce free radical mediated disorders and as natural alternative for food preservation.

  19. Advanced Therapeutic Gastrointestinal Endoscopy in Children - Today and Tomorrow.

    Science.gov (United States)

    Nabi, Zaheer; Reddy, Duvvur Nageshwar

    2017-12-12

    Gastrointestinal (GI) endoscopy plays an indispensable role in the diagnosis and management of various pediatric GI disorders. While the pace of development of pediatric GI endoscopy has increased over the years, it remains sluggish compared to the advancements in GI endoscopic interventions available in adults. The predominant reasons that explain this observation include lack of formal training courses in advanced pediatric GI interventions, economic constraints in establishing a pediatric endoscopy unit, and unavailability of pediatric-specific devices and accessories. However, the situation is changing and more pediatric GI specialists are now performing complex GI procedures such as endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography for various pancreatico-biliary diseases and more recently, per-oral endoscopic myotomy for achalasia cardia. Endoscopic procedures are associated with reduced morbidity and mortality compared to open surgery for GI disorders. Notable examples include chronic pancreatitis, pancreatic fluid collections, various biliary diseases, and achalasia cardia for which previously open surgery was the treatment modality of choice. A solid body of evidence supports the safety and efficacy of endoscopic management in adults. However, additions continue to be made to literature describing the pediatric population. An important consideration in children includes size of children, which in turn determines the selection of endoscopes and type of sedation that can be used for the procedure.

  20. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-02-07

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

  1. Advances in therapeutic strategies for the treatment of pruritus.

    Science.gov (United States)

    Stull, Carolyn; Lavery, Michael J; Yosipovitch, Gil

    2016-01-01

    Chronic pruritus is a common symptom that arises from both dermatologic and non-dermatologic conditions including chronic kidney disease, cholestasis, lymphoma and neuropathy. Over the past decade, research has elucidated many of the receptors, neuropeptides and cytokines involved in itch sensation and transmission. In addition, the first biomarker for cholestatic itch has been discovered. These findings have led to the development of a host of novel antipruritic medications, both on the market and in the pipeline. A summary of new and emerging treatments for pruritus, as well as possible targets for future therapeutic development is provided. At present, there is no universally effective treatment available for all types of chronic pruritus. A combination of topical and systemic therapies addressing peripheral mediators, and a top-down approach targeting the brain and spinal cord, seems preferable to a single agent approach. Neural hypersensitization plays a significant role in many forms of chronic pruritus and may be downregulated by new treatments. In addition, specific neuropeptides are now targeted by novel antipruritic therapies. Furthermore, targeted biologic agents are anticipated to play a significant role in treating pruritus of inflammatory origin.

  2. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  3. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

    Science.gov (United States)

    Corcoran, David

    2018-01-01

    The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

  4. Rituximab as a therapeutic option for patients with advanced melanoma.

    Science.gov (United States)

    Winkler, Julia K; Schiller, Matthias; Bender, Carolin; Enk, Alexander H; Hassel, Jessica C

    2018-03-07

    Treatment of metastatic melanoma remains challenging, despite a variety of new and promising immunotherapeutic and targeted approaches to therapy. New treatment options are still needed to improve long-term tumour control. We present a case series of seven patients with metastatic melanoma who were treated individually with the anti-CD20 antibody rituximab between July 2014 and July 2015. Two of the patients were treated in an adjuvant setting. All patients had already received a variety of treatments. During an induction phase, the administration of four cycles of weekly rituximab 375 mg/m 2 body surface area was planned. After imaging, patients with stable disease continued therapy with rituximab 375 mg/m 2 body surface area every 4 weeks up to a maximum of 24 weeks. Two patients experienced grade 2 infusion reactions during the first infusion. Otherwise, treatment was well tolerated and there were no grade 3 or 4 side effects. Staging after the induction phase showed stable disease in five patients, and two patients had progressive disease. Median progression-free survival was 6.3 months (95% CI 4.97-7.53), median overall survival was 14.7 months (95% CI 4.52-24.94), and one patient was still alive in December 2016. In conclusion, rituximab might be a therapeutic option for metastatic melanoma. However, further studies on rituximab among larger patient cohorts are warranted. Evaluation of therapy in an adjuvant setting or in combination with other systemic treatment might, therefore, be of particular interest.

  5. Advances in genetic therapeutic strategies for Duchenne muscular dystrophy.

    Science.gov (United States)

    Guiraud, Simon; Chen, Huijia; Burns, David T; Davies, Kay E

    2015-12-01

    What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X-linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene-replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re-establish muscle function. © 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  6. Antioxidants as therapeutics in the intensive care unit: Have we ticked the redox boxes?

    Science.gov (United States)

    Margaritelis, Nikos V

    2016-09-01

    Critically ill patients are under oxidative stress and antioxidant administration reasonably emerged as a promising approach to combat the aberrant redox homeostasis in this patient cohort. However, the results of the antioxidant treatments in the intensive care unit are conflicting and inconclusive. The main objective of the present review is to highlight some inherent, yet widely overlooked redox-related issues about the equivocal effectiveness of antioxidants in the intensive care unit, beyond methodological considerations. In particular, the discrepancy in the literature partially stems from: (1) the largely unspecified role of reactive species in disease onset and progression, (2) our fragmentary understanding on the interplay between inflammation and oxidative stress, (3) the complex spatiotemporal specificity of in vivo redox biology, (4) the pleiotropic effects of antioxidants and (5) the divergent effects of antioxidants according to the temporal administration pattern. In addition, two novel and sophisticated practices with promising pre-clinical results are presented: (1) the selective neutralization of reactive species in key organelles after they are formed (i.e., in mitochondria) and (2) the targeted complete inhibition of dominant reactive species sources (i.e., NADPH oxidases). Finally, the reductive potential of NADPH as a key pharmacological target for redox therapies is rationalized. In light of the above, the recontextualization of knowledge from basic redox biology to translational medicine seems imperative to perform more realistic in vivo studies in the fast-growing field of critical care pharmacology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Evaluation of antioxidant, anti-inflammatory, and antiulcer properties of Vaccinium leschenaultii Wight: A therapeutic supplement

    Directory of Open Access Journals (Sweden)

    Poornima Nagulsamy

    2015-09-01

    Full Text Available In folklore systems of medicine, bilberry fruit and leaf extracts have been used for the treatment of diarrhoea, dysentery, diabetes, inflammation, and ulcer. The present study was to determine antioxidant, anti-inflammatory, and antiulcerogenic activities of Vaccinium leschenaultii Wight leaf and fruit. The phenolic, tannin, and flavonoid contents of V. leschenaultii leaf and fruit were quantified and were subjected to assess their antioxidant potential using various in vitro systems such as 1, 1 diphenyl-2-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical scavenging, phosphomolybdenum, and ferric reducing antioxidant power reduction activities. Based on the antioxidant potential, acetone and methanol extracts of leaf and fruit were used to evaluate the anti-inflammatory activity and protective effect against ethanol-induced gastric damage in a rat model. The quantification of secondary metabolites shows that the phenolic, flavonoid, and tannin contents are higher in methanol extracts of fruit and leaf. The results of antioxidant assays exhibited that the methanol extracts of leaf possesses better 1, 1 diphenyl-2-picrylhydrazyl radical scavenging and ferric reducing power activity. Oral administration of the acetone fruit and leaf extracts of V. leschenaultii were capable of reducing the edema formation in rats against carrageenan and egg albumin induced inflammation. Moreover, leaf and fruit acetone extracts at the dose of 400 mg/kg highly inhibited ulcer formation. The study concluded that the plant substances such as total phenols, flavonoids along with appreciable antioxidant potential could be the supportive evidence to prove both the anti-inflammatory and antiulcer activities of V. leschenaultii. The traditional importance of this plant will help to reveal the potential of plant to provide alternative phytotherapeutics for human health.

  8. Antioxidant Phytochemicals in Fresh Produce: Exploitation of Genotype Variation and Advancements in Analytical Protocols

    Directory of Open Access Journals (Sweden)

    George A. Manganaris

    2018-02-01

    Full Text Available Horticultural commodities (fruit and vegetables are the major dietary source of several bioactive compounds of high nutraceutical value for humans, including polyphenols, carotenoids and vitamins. The aim of the current review was dual. Firstly, toward the eventual enhancement of horticultural crops with bio-functional compounds, the natural genetic variation in antioxidants found in different species and cultivars/genotypes is underlined. Notably, some landraces and/or traditional cultivars have been characterized by substantially higher phytochemical content, i.e., small tomato of Santorini island (cv. “Tomataki Santorinis” possesses appreciably high amounts of ascorbic acid (AsA. The systematic screening of key bioactive compounds in a wide range of germplasm for the identification of promising genotypes and the restoration of key gene fractions from wild species and landraces may help in reducing the loss of agro-biodiversity, creating a healthier “gene pool” as the basis of future adaptation. Toward this direction, large scale comparative studies in different cultivars/genotypes of a given species provide useful insights about the ones of higher nutritional value. Secondly, the advancements in the employment of analytical techniques to determine the antioxidant potential through a convenient, easy and fast way are outlined. Such analytical techniques include electron paramagnetic resonance (EPR and infrared (IR spectroscopy, electrochemical, and chemometric methods, flow injection analysis (FIA, optical sensors, and high resolution screening (HRS. Taking into consideration that fruits and vegetables are complex mixtures of water- and lipid-soluble antioxidants, the exploitation of chemometrics to develop “omics” platforms (i.e., metabolomics, foodomics is a promising tool for researchers to decode and/or predict antioxidant activity of fresh produce. For industry, the use of optical sensors and IR spectroscopy is recommended to

  9. 77 FR 46444 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics (GREAT); Public Workshop

    Science.gov (United States)

    2012-08-03

    ... disease is either an efficacy or safety outcome measure. Particpation In the Public Workshop: Registration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics (GREAT); Public Workshop AGENCY: Food and...

  10. Influence of naturally occurring antioxidants on magnetic nanoparticles: risks, benefits, and possible therapeutic applications.

    Science.gov (United States)

    Durdík, Stefan; Vrbovská, Hanka; Olas, Adam; Babincová, Melánia

    2013-06-01

    We have studied interaction of well known antioxidant L-ascorbic acid with magnetic nanoparticles containing insoluble Fe(III) in their core. In analogy with ferritin, mobilization of iron in the form of water soluble Fe(II) was observed, especially pronounced at higher temperatures. In the presence of hydrogen peroxide cytotoxic hydroxyl radicals are produced. These results suggest possible harmful effects of widely used magnetic nanoparticles as a MRI contrast agents in combination with overload of organism with ascorbic acid in some specific conditions, like fever of patient. On the other hand combination of magnetic nanoparticles and ascorbic acid may be used for a cancer therapy using alternating magnetic field for the release of Fe(II) via Néel relaxation of magnetic moment of used nanoparticles. We have further found that lipoic acid is an efficient antioxidant scavenging hydroxyl radicals produced by Fenton reaction from Fe(II).

  11. [Advances in Neurological Therapeutics for Friedreich Ataxia and Machado-Joseph Disease].

    Science.gov (United States)

    Yabe, Ichiro; Sasaki, Hidenao

    2017-08-01

    We reviewed advances in therapeutics for both Friedreich ataxia and Machado-Joseph disease. Various clinical trials have been carried out, mainly for Friedreich ataxia; however, the therapeutic reports from these trials have not provided much evidence for success. Some interesting clinical trials have been reported, and further developments are expected. Regenerative therapy using umbilical cord mesenchymal stem cells and a therapeutic study investigating a new pathomechanism in animal and/or cell culture studies were reported. We expect that these results will translate to therapeutic strategies for patients with these disorders. In addition, biomarkers play an important role when novel treatments are discovered and clinical trials are performed: hence at present, a number of biomarkers such as gait analysis by triaxial accelerometers and prism adaptation of hand-reaching movements, are being examined.

  12. Measures of combined antioxidant and pro-oxidant exposures and risk of overall and advanced stage prostate cancer.

    Science.gov (United States)

    Geybels, Milan S; Verhage, Bas A J; van Schooten, Frederik J; van den Brandt, Piet A

    2012-11-01

    Oxidative stress is possibly related to prostate carcinogenesis. We constructed a dietary antioxidant score, which is a measure of combined antioxidant exposures, and an oxidative balance score (OBS), which is a measure of combined antioxidant and pro-oxidant exposures. We hypothesized that both scores are inversely associated with the risk of prostate cancer (PCa). We conducted a case-cohort study among 58,279 men in the Netherlands Cohort Study. Cohort members completed a baseline questionnaire. From 1986 to 2003, 3451 patients with PCa were identified including 1196 advanced cancers (stage III/IV). The antioxidant score and the OBS were created by summing quartile and category scores of individual score constituents, which had an equal weight. Pro-oxidants were scored in the opposite way to antioxidants. Both the antioxidant score and OBS were not associated with risk of overall PCa or PCa subgroups on the basis of disease stage. Most score constituents were not associated with the risk of PCa. Total catechin intake was associated with a decreased risk of stage IV PCa (greatest vs. lowest quartile: hazard ratio, 0.76; 95% confidence interval, 0.59-0.98). The antioxidant score and OBS were not associated with risk of overall and advanced-stage PCa. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Mitochondria-targeted Antioxidants as a Prospective Therapeutic Strategy for Multiple Sclerosis.

    Science.gov (United States)

    Fetisova, Elena; Chernyak, Boris; Korshunova, Galina; Muntyan, Maria; Skulachev, Vladimir

    2017-01-01

    Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/ remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter. In this review, we discuss a possible role of mitochondrial reactive oxygen species (mtROS) in MS pathogenesis, mechanisms of mtROS generation and effects of some mitochondria-targeted antioxidants as potential components of MS therapy. In the early phase of MS, mtROS stimulate NLRP3 inflammasomes, which is critical for the formation of local inflammatory lesions. Later, mtROS contribute to blood-brain barrier disruption induced by mediators of inflammation, followed by infiltration of leukocytes. ROS generated by leukocytes and activated microglia promote mitochondrial dysfunction and oligodendrocyte cell death. In the progressive phase, neurodegeneration also depends on excessive mtROS generation. Currently, only a few immunomodulatory drugs are approved for treatment of MS. These drugs mainly reduce the number of relapses but do not stop MS progression. Certain dietary and synthetic antioxidants have demonstrated encouraging results in animal models of MS but were ineffective in the completed clinical trials. Novel mitochondria-targeted antioxidants could be promising components of combined programs for MS therapy considering that they can be applied at extremely low doses and concurrently demonstrate anti-inflammatory and neuroprotective activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

    Directory of Open Access Journals (Sweden)

    Diana Rosa Fernández Ruiz

    2017-02-01

    Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

  15. Oxidative stress and antioxidant activity in hypothermia and rewarming: can RONS modulate the beneficial effects of therapeutic hypothermia?

    Science.gov (United States)

    Alva, Norma; Palomeque, Jesús; Carbonell, Teresa

    2013-01-01

    Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia.

  16. Oxidative Stress and Antioxidant Activity in Hypothermia and Rewarming: Can RONS Modulate the Beneficial Effects of Therapeutic Hypothermia?

    Directory of Open Access Journals (Sweden)

    Norma Alva

    2013-01-01

    Full Text Available Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS, followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia.

  17. Therapeutic effects of gingerol on hematopoietic and antioxidative damage of 60Co γ-rays irradiated mice

    International Nuclear Information System (INIS)

    Geng Yanyan; Xie Zhenfei; Zhou Yu; Zeng Xianyin

    2012-01-01

    18 female Kunming mice were chosen and randomly divided into three groups, and the therapeutic effects of gingerol on hemopoietic and antioxidative system in liver of 60 Co γ-rays irradiated mice were developed in this study. Control group was given distilled water intragastrically once a day for five days. Mice in the irradiated group and irradiated + gingerol group were both irradiated at 3 Gy of 60 Co γ-rays and were given distilled water and gingerol intragastrically within 30 min after irradiation respectively, once a day for five days. The mice were sacrificed and sampled in 48 hours after intragastric administration. Compared with control group, the relative spleen index and WBC numbers significantly decreased (P 60 Co γ-rays irradiated mice. (authors)

  18. Advances in chromosomal translocations and fusion genes in sarcomas and potential therapeutic applications.

    Science.gov (United States)

    Xiao, Xin; Garbutt, Cassandra C; Hornicek, Francis; Guo, Zheng; Duan, Zhenfeng

    2018-02-01

    Chromosomal translocations and fusion genes are very common in human cancer especially in subtypes of sarcomas, such as rhabdomyosarcoma, Ewing's sarcoma, synovial sarcoma and liposarcoma. The discovery of novel chromosomal translocations and fusion genes in different tumors are due to the advancement of next-generation sequencing (NGS) technologies such as whole genome sequencing. Recently, many novel chromosomal translocations and gene fusions have been identified in different types of sarcoma through NGS approaches. In addition to previously known sarcoma fusion genes, these novel specific fusion genes and associated molecular events represent important targets for novel therapeutic approaches in the treatment of sarcomas. This review focuses on recent advances in chromosomal translocations and fusion genes in sarcomas and their potential therapeutic applications in the treatment of sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    H.A. Daniel Lagassé

    2017-02-01

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

  20. Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2013-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.

  1. Herb-Herb Combination for Therapeutic Enhancement and Advancement: Theory, Practice and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Christopher Wai Kei Lam

    2013-05-01

    Full Text Available Herb-herb combinations have been used in Chinese medicine practice for thousands of years, yet scientific evidence of their therapeutic benefits is lacking. With increasing interest in shifting from the one-drug-one-target paradigm to combination therapy or polypharmacy to achieve therapeutic benefits for a number of diseases, there is momentum to explore new knowledge by tapping the past empirical experiences of herb-herb combinations. This review presents an overview of the traditional concept and practice of herb-herb combination in Chinese medicine, and highlights the available scientific and clinical evidence to support the combined use of herbs. It is hoped that such information would provide a lead for developing new approaches for future therapeutic advancement and pharmaceutical product development. Very likely modern technologies combined with innovative research for the quality control of herbal products, identification of active components and understanding of the molecular mechanism, followed by well-designed animal and clinical studies would pave the way in advancing the wealth of empirical knowledge from herb-herb combination to new therapeutic modalities.

  2. Resveratrol: review on therapeutic potential and recent advances in drug delivery.

    Science.gov (United States)

    Pangeni, Rudra; Sahni, Jasjeet K; Ali, Javed; Sharma, Shrestha; Baboota, Sanjula

    2014-08-01

    Natural products have seen a wide range of acceptability for the prevention and treatment of diseases throughout history. Resveratrol, a member of the stilbene family, has been found to potentially exhibit anticancer, antiangiogenic, immunomodulatory and cardioprotective activities as well as being an antioxidant. This is in addition to its usefulness in the treatment of neurodegenerative disease, diabetes and cardiac ailments. Currently, various studies have revealed that resveratrol is a potential drug candidate with multi-spectrum therapeutic application. This review aims to describe the various studies supporting the wide range of pharmacological activities of resveratrol. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of resveratrol such as solubility, stability and bioavailability. Resveratrol demonstrated its ability to be a potential drug candidate for the treatment of different ailments due to its potent antioxidant properties. To improve the drug stability, increase the bioavailability and minimize side-effects of resveratrol, novel drug delivery systems have been formulated to bring this potential candidate to the first line of disease treatment.

  3. Advances in the proteomic discovery of novel therapeutic targets in cancer

    Directory of Open Access Journals (Sweden)

    Guo S

    2013-10-01

    Full Text Available Shanchun Guo,1 Jin Zou,2 Guangdi Wang3 1Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 2Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA; 3Research Centers in Minority Institutions Cancer Research Program, Xavier University of Louisiana, New Orleans, LA, USA Abstract: Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed. Keywords: proteomics, cancer, therapeutic target, signaling network, tumorigenesis

  4. Role of simvastatin and/or antioxidant vitamins in therapeutic angiogenesis in experimental diabetic hindlimb ischemia: effects on capillary density, angiogenesis markers, and oxidative stress.

    Science.gov (United States)

    El-Azab, Mona F; Hazem, Reem M; Moustafa, Yasser M

    2012-09-05

    Therapeutic angiogenesis has emerged as an attractive approach for the management of peripheral arterial disease in diabetic patients. Oxidative stress generated and aggravated by prolonged hyperglycemia may interfere with and destroy the newly formed blood vessels. Angiogenic effect of simvastatin has been reported; however, its exact mechanism is yet to be evaluated. In addition, the exact role of antioxidant vitamins in diabetic peripheral arterial disease is still controversial. The present study was undertaken to investigate the therapeutic potential of simvastatin and antioxidant vitamins (E and C) and their combined effects on angiogenesis in diabetic hind-limb ischemia. Streptozotocin diabetic rats were treated for 6 weeks with simvastatin either alone or in combination with vitamin E or vitamin C. Parameters of angiogenesis, nitric oxide, heme oxygenase-1 (HO-1), and oxidative stress markers were evaluated. CD31 immunostaining revealed an increased capillary density in ischemic gastrocnemious tissue of diabetic rats treated with either simvastatin or its combination with vitamin C. This effect was accompanied by up-regulated plasma levels of HO-1, nitric oxide, vascular endothelial growth factor (VEGF) and its intra-muscular receptor type-2 (Flk-1). Tissue reduced glutathione and antioxidant enzymes activities were normalized in groups treated with antioxidant vitamins or their combination with simvastatin with concomitant blunting of lipid peroxidation. Vitamins E and C, through their antioxidant effects, evidently enhanced the angiogenic effect of simvastatin in ischemic diabetic muscle. Hence, the use of antioxidant vitamins combined with statins to induce therapeutic angiogenesis is a promising strategy in the management of diabetes-associated peripheral arterial disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. [New medicines registered in Brazil: can they be considered as a therapeutic advance?].

    Science.gov (United States)

    Gava, Cíntia Maria; Bermudez, Jorge Antonio Zepeda; Pepe, Vera Lúcia Edais; dos Reis, André Luiz Almeida

    2010-11-01

    Technological advances in the last century led to the discovery of a variety of medicines. Their introduction, not always with significant therapeutic gains and not without risk, made the register by regulatory agency an important moment in their evaluation. The aim of this study was to analyze 49 new medicines registered by the National Health Surveillance Agency (Anvisa), between the years 2000 and 2002 and commercialized in the first half of 2003, considering their therapeutic advantage. Most medicines (42.9%) were from the American pharmaceutical industry. Most of them (63.3%) were classified as a new molecular entity, followed by the new fixed dose combinations (28.6%). Seventy-five percent were registered at the Food and Drug Administration (FDA). It was possible to obtain the classification of its New Drug Application (NDA) according to their therapeutic potential to 33 medicines and 57.6% of them were classified as standard. Most of the new registered medicines did not provide any therapeutic advantage. It is suggested that Anvisa disseminate the analysis information on innovation, efficacy, safety, brought (or not) by new drugs. This kind of information is important to consumers, health professionals and health managers.

  6. Joint conference on the impact of EU legislation on therapeutic advance.

    Science.gov (United States)

    Forgó, Nikolaus; Hildebrandt, Martin

    2013-12-01

    On October 11, 2012, two FP7-funded Research Consortia, CONTRACT (Consent in a Trial and Care Environment) and Academic GMP, held a Joint Conference in Brussels entitled "The Impact of EU Legislation on Therapeutic Advance." Academic researchers including stem cell transplant physicians and cell therapy specialists, legal advocates and representatives from industry, regulatory authorities and patient advocacy groups met with members of the European Parliament and the European Commission. This article summarizes important points of discussion and detailed proposals for improvement. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Choi, Won; Lee, Jee Bum; Cui, Lian; Li, Ying; Li, Zhengri; Choi, Ji Suk; Lee, Hyo Seok; Yoon, Kyung Chul

    2016-01-01

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

  8. New therapeutic directions for advanced pancreatic cancer: cell cycle inhibitors, stromal modifiers and conjugated therapies.

    Science.gov (United States)

    Matera, Robert; Saif, Muhammad Wasif

    2017-09-01

    Pancreatic adenocarcinoma is a devastating malignancy with an extremely poor prognosis. These tumors progress rapidly and somewhat silently with few specific symptoms and are relatively resistant to chemotherapeutic agents. Many agents, including cell cycle inhibitors, are under development for the treatment of this cancer for which there are disappointingly few treatment options. Areas covered: Here we outline the existing approved treatments for advanced pancreatic disease and discuss a range of novel therapies currently under development including cell cycle inhibitors, stromal modifiers and conjugated therapies. We also describe the current state of the pancreatic cancer therapeutics market both past and future. Expert opinion: Despite the recent explosion of novel therapies with an array of unique targets, the core treatment of pancreatic cancer still with traditional cytotoxic agents with a few exceptions. However, as these novel treatments move through the pipeline, we are hopeful that there will soon be a number of effective options for patients with advanced pancreatic cancer.

  9. A novel therapeutics agent: antioxidant effects of hydroxylfasudil on rat kidney and liver tissues in a protamine sulphate-induced cystitis rat model; preliminary results.

    Science.gov (United States)

    Bozkurt, Aliseydi; Budak, Harun; Erol, Huseyin Serkan; Can, Serpil; Mercantepe, Tolga; Akin, Yigit; Ozbey, Isa; Cankaya, Murat; Halici, Mesut Bunyamin; Coban, T Abdulkadir

    2018-03-09

    Cystitis is defined as an inflammation of the bladder caused by a bacterial infection, and it can be dangerous and painful when it spreads through the internal organs. In this study, antioxidant effects of hydroxylfasudil (HF) at the enzymatic and molecular level on kidney and liver tissues in cystitis rat model, which is caused by inflammation of the rat bladder with a protamine sulphate (PS), was examined. Quantitative changes of reduced glutathione (GSH) and lipid peroxidation (LPO) levels, which are a marker for oxidative stress, were determined in rat kidney and liver tissues for each groups. And then molecular and biochemical impact of HF treatment on antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) in cystitis model were studied. The results suggest that HF could be beneficial to the renal and hepatic antioxidant system. Thus, HF might be used as a novel therapeutics agent to eliminate interstitial cystitis.

  10. Prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease.

    Science.gov (United States)

    Miletić, Jadranka; Drakulić, Dunja; Pejić, Snežana; Petković, Marijana; Ilić, Tihomir V; Miljković, Milica; Stefanović, Aleksandra; Prostran, Milica; Stojanov, Marina

    2017-12-04

    Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity. The aim of this study was to evaluate the levels of the above-mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status. The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant-antioxidant balance (p = 0.02). Relation between oxidant-antioxidant status was further supported by observed positive correlation between 4-hydroxynonenal (p = 0.04) and prooxidant-antioxidant balance (p = 0.03). Finally, the multivariate analysis indicated that prooxidant-antioxidant balance and malondialdehyde were partially determined by gender (10.6% and 7.6%) and Hoehn and Yahr scores (13.6% and 18.8%), while Hoehn and Yahr scores contributed to the variance of advanced oxidation protein products with 13.2%. Our results indicate the higher level of oxidative stress (oxidant-antioxidant imbalance) and possible relation of several markers with gender and disease stage in patients with Parkinson's disease. The analyzed markers could be used to specify the severity of oxidative stress; however, their potential value should be analyzed in further studies.

  11. Development and Implementation of an Advanced Therapeutic Communication Course: An Interprofessional Collaboration.

    Science.gov (United States)

    Schwind, Jasna K; McCay, Elizabeth; Metersky, Kateryna; Martin, Jennifer

    2016-10-01

    Interprofessional education and practice have been gaining recognition during the past decade. However, little has been written on person-centered care (PCC) within interprofessional practice and how it could be taught to interprofessional learners. A key element of PCC is therapeutic communication. Consequently, a group of interprofessional faculty innovated a graduate-level elective course on advanced therapeutic communication where interprofessional learners together explore PCC within interprofessional care. The course curriculum is underpinned by mindfulness in education, nonviolent communication, and reflective writing. Various teaching- learning strategies, including creative self-expression, are also used. The created competencies and conceptual framework may be used by other educators in creating a similar interprofessional course. Interprofessional learners gained a deeper and broader understanding of PCC in interprofessional care. On the basis of this undertaking, the faculty gained a deeper appreciation for interprofessional collaboration in the development of innovative educational methodologies that advance interprofessional teamwork in education and professional practice. [J Nurs Educ. 2016;55(10):592-597.]. Copyright 2016, SLACK Incorporated.

  12. Prognosis and therapeutic response according to the world health organization histological classification in advanced thymoma

    International Nuclear Information System (INIS)

    Tagawa, Tetsuzo; Kometani, Takuro; Yamazaki, Koji

    2011-01-01

    The clinical efficacy of the World Health Organization (WHO) classification of thymoma has been reported to be a prognostic factor for patients with thymomas. This study focuses on the relationship between the therapeutic response and the WHO histological classification in patients with advanced thymoma. A retrospective review was performed on 22 patients with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1, 7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3, respectively. Surgery was performed on 10 patients. There were 2 complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of 18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy, chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The response rate in 9 patients with type A-B2 was significantly better than that in 9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P=0.0001). Only the WHO classification was significantly associated with survival, with type B3 having a worse prognosis than A-B2 (P=0.01). Type B3 thymoma showed a lower response rate to treatments and thus shorter survival. The WHO classification is a good predictive factor for therapeutic response in advanced thymoma. (author)

  13. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

    Directory of Open Access Journals (Sweden)

    Sathish Sundar Dhilip Kumar

    2018-04-01

    Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  14. A new therapeutic assessment score for advanced hepatocellular carcinoma patients receiving hepatic arterial infusion chemotherapy.

    Directory of Open Access Journals (Sweden)

    Issei Saeki

    Full Text Available Hepatic arterial infusion chemotherapy (HAIC is an option for treating advanced hepatocellular carcinoma (HCC. Because of the poor prognosis in HAIC non-responders, it is important to identify patients who may benefit from continuous HAIC treatment; however, there are currently no therapeutic assessment scores for this identification. Therefore, we aimed to establish a new therapeutic assessment score for such patients.We retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP and/or des-gamma-carboxy prothrombin (DCP levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks; a positive-response was defined as a reduction of ≥ 20% from baseline.Multivariate analysis identified DCP response (odds ratio 16.03, p < 0.001 as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018, AFP response (HR 2.17, p = 0.007, and DCP response (HR 1.90, p = 0.030 were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤ 1 vs. ≥ 2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003.The ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.

  15. Inhibition of Advanced Glycation End-Product Formation and Antioxidant Activity by Extracts and Polyphenols from Scutellaria alpina L. and S. altissima L.

    Directory of Open Access Journals (Sweden)

    Izabela Grzegorczyk-Karolak

    2016-06-01

    Full Text Available Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE in vitro. S. alpina, which is richer in polyphenolic compounds, had strong antiglycation properties. These extracts demonstrated also high activity in the FRAP (ferric-reducing antioxidant power, antiradical (DPPH and lipid peroxidation inhibition assays. Among the pure compounds, baicalin was the strongest glycation inhibitor (90.4% inhibition at 100 μg/mL, followed by luteolin (85.4%. Two other flavone glycosides had about half of this activity. Verbascoside was similar to the reference drug aminoguanidine (71.2% and 75.9%, respectively. The strong correlation observed between AGE inhibition and total flavonoid content indicated that flavonoids contribute significantly to antiglycation properties. A positive correlation was also observed between antiglycative and antioxidant activities. The studied skullcap species can be considered as a potential source of therapeutic agents for hyperglycemia-related disorders.

  16. Hyperhidrosis: review of recent advances and new therapeutic options for primary hyperhidrosis.

    Science.gov (United States)

    Brown, Ashley L; Gordon, Jennifer; Hill, Samantha

    2014-08-01

    Primary focal hyperhidrosis is a common condition that negatively impacts quality of life for many pediatric patients and can be challenging to treat. Standard treatments for hyperhidrosis can be used with success in many patients, and newer therapies and techniques offer options that have demonstrated efficacy and safety. This review highlights standard therapies for primary focal hyperhidrosis as well as the most recent technique advancements and alternative treatment options. The standard approach to treating primary focal hyperhidrosis remains initiation of topical preparations, followed by advancement to systemic medications, local administration of medication and/or surgical procedures. Recent studies focus on enhancing tolerability of topical preparations as well as evaluating the efficacy of neuromodulator injections, oral anticholinergic medications and laser therapy. Microwave technology has also been introduced for the treatment of focal hyperhidrosis with promising results. Many therapies exist for hyperhidrosis, and each treatment plan must be evaluated on a patient-by-patient basis. Advances in standard therapies and emergence of new treatment techniques are the main emphases of current published literature on hyperhidrosis. This article presents recent therapeutic options as well as updates on more established strategies to help practitioners treat this challenging condition.

  17. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV dysfunction, and heart failure (HF. The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure.

  18. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ji Young Yhee

    2016-09-01

    Full Text Available Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD, cystic fibrosis (CF, idiopathic pulmonary fibrosis (IPF, and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed.

  19. Development of gastroenterology and hepatology in Iran: Part II- advances in research and therapeutic modalities.

    Science.gov (United States)

    Saberifiroozi, Mehdi; Mir-Madjlessi, Seid-Hossein

    2009-09-01

    Following the establishment of Gastroenterology and Hepatology Fellowship Programs in 1987, significant developments in research and health care delivery have been achieved. The number of published articles has increased significantly and now more than 10 approved research centers are involved in several longitudinal and population based studies in GI epidemiology, viral hepatitis and GI oncology around the country. Before 1987 less than 50 gastroenterologists were working in the country, but now more than 300 gastroenterologists are involved in public and private health care delivery systems. Advanced diagnostic and therapeutic endoscopic procedures and complex surgical procedures such as liver transplantation are a routine now. These achievements are indicative of hard work and determination of dedicated physicians after the Islamic Revolution, and the support of governmental and non-governmental sectors. The future prospect of development in the discipline of gastroenterology and hepatology in Iran seems to be very encouraging.

  20. Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Chien-Ming Liu

    2015-01-01

    Full Text Available Introduction. Epidermal growth factor receptor (EGFR mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells and A549 (EGFR wild type; Gefitinib-resistant cells cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.

  1. Mechanical Myocardial Injury and Angiogenesis: An Association with Therapeutic Potential for Advanced Ischemic Coronary Artery Disease.

    Science.gov (United States)

    Slepian, Marvin J.

    2001-08-01

    The healing response of tissue after mechanical injury is a highly evolved complex response that serves as a natural defense mechanism. Tissue wounds typically heal in a temporal sequence of stages. A vital phase of wound healing is the generation of loose reparative tissue that is neovascularized and rich in angiogenic substrates--that of granulation tissue formation. A therapeutic strategy that has emerged for the treatment of patients with advanced atherosclerotic ischemic coronary disease is to therapeutically manipulate the wound healing process and induce injury in the myocardium to stimulate islands of neovascularization. This paper reviews the response of tissue, particularly the myocardium, to various forms of injury. Also discussed is the emerging hypothesis of a threshold of injury (balancing adequate injury to induce neovascularizatioin versus excessive injury resulting in adjacent myocardial damage with contractile dysfunction without additional angiogenic benefit). Initial animal and human studies from our laboratory and that of collaborators, with a new method of injury-induced angiogenesis referred to as mechanical myocardial channeling, are reviewed.

  2. Comparison of therapeutic effects of L-Thyroxin, apelin and a combination of both on antioxidant enzymes in the heart of PTU-induced hypothyroid rats

    Directory of Open Access Journals (Sweden)

    Farzaneh Faraji Shahrivar

    Full Text Available Atherosclerosis is one of the common disorders among hypothyroidism, which, increased the risk of cardiovascular diseases. Reactive oxygen species are associated with atherosclerosis development. Antioxidant defense systems are the scavenger for free radicals. Apelin is an endogenous ligand for the APJ receptor (apelin receptor that exists in most tissues, acts as an adiponectin. It has been identified that apelin administration, improve the antioxidant capacity (TAC. Therefore, this study was conducted to assess, therapeutic effects of apelin, T4 (L-Thyroxin or both on antioxidant capacity in 6-propyl-2-thiouracil (PTU-induced hypothyroid rats. Forty male Wistar rats were randomly assigned into five groups: C: control group; P group (hypothyroid: PTU (0.05 % administration for six weeks; P+A, P+T and P+A+T groups: after 4 weeks of PTU administration, animals treated with Apelin (200 μg/kg/day, ip T4 (0.02 µg/g/day, gavage and apelin+T4; for two weeks respectively accompanied by PTU administration. Aplein administration in P+A group and P+A+T group had beneficial effect to lowering of malondialdehyde (MDA content as compared to hypothyroid group (8.52±0.64 and 8.53±1 vs. 13.67±1.64 nmol/g tissue, P<0.05 and also had increasing effect on Superoxide dismutase (SOD and glutathion peroxidase (GPx activity and the total antioxidant capacity (TAC content compared to the hypothyroid group. This study showed that apelin was able to improve the oxidant-antioxidant balance in the heart tissue of the hypothyroid rats by elevating of antioxidant enzyme activity.

  3. Strategic management of therapeutic advances: experience with colony-stimulating factors.

    Science.gov (United States)

    Shane, R; Nishimura, L

    1994-09-01

    Recent therapeutic advances offer significant opportunities for improved patient outcomes while challenging our ability to deliver these outcomes in a cost-effective manner. This report describes the strategies for managing such advanced therapies--specifically, the recently introduced colony stimulating factors (CSFs)--that have been adopted at Cedars-Sinai Medical Center. Based on the principles of Continuous Quality Improvement (CQI), our approach begins with a multidisciplinary task force that develops and continuously refines guidelines for use of these agents. To provide immediate feedback when physician orders do not conform to the guidelines, the pharmacist notifies a physician expert, who promptly contacts the prescriber for a discussion of the case and how the guidelines do or do not apply. Since the introduction of CSFs, cost per admission has declined from $983 to $729 (26%) for oncology patients and from $737 to $281 (62%) for HIV patients. Although it is impossible to rigorously establish how much of this decrease has resulted from our proactive management strategy, costs have consistently decreased following each task force intervention.

  4. A Practice-Based Theory of Healing Through Therapeutic Touch: Advancing Holistic Nursing Practice.

    Science.gov (United States)

    Hanley, Mary Anne; Coppa, Denise; Shields, Deborah

    2017-08-01

    For nearly 50 years, Therapeutic Touch (TT) has contributed to advancing holistic nursing practice and has been recognized as a uniquely human approach to healing. This narrative explores the development of a practice-based theory of healing through TT, which occurred between 2010 and 2016. Through the in-depth self-inquiry of participatory reflective dialogue in concert with constant narrative analysis, TT practitioners revealed the meaning of healing within the context of their TT practice. As the community of TT experts participated in an iterative process of small group and community dialogues with analysis and synthesis of emerging themes, the assumptions and concepts central to a theory of healing emerged, were clarified and verified. Exemplars of practice illustrate the concepts. A model of the theory of healing illuminates the movement and relationship among concepts and evolved over time. Feedback from nursing and inter-professional practitioners indicate that the theory of healing, while situated within the context of TT, may be useful in advancing holistic nursing practice, informing healing and caring approaches, stimulating research and education, and contributing to future transformations in health care.

  5. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity

    Science.gov (United States)

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  6. Therapeutic Results of Concurrent Chemoradiation in Locally Advanced Uterine Cervical Cancer

    International Nuclear Information System (INIS)

    Kang, Seung Hee; Suh, Hyun Suk; Yang, Kwang Mo; Lee, Eung Soo; Park, Sung Kwon

    1995-01-01

    Purpose : Despite a development for therapeutic machines and advance in modern radiation therapy techniques, locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate. Combination of chemotherapy and radiotherapy demonstrated benefit in improving local control and possibly the overall survival. Our study was performed to evaluate effect of concurrent chemoradiation on locally advanced uterine cervical cancer. Methods and Materials : Twenty six patients with locally advanced stage(FIGO stage IIB with ≥ 5 cm in diameter, III, IVA) were treated with combination of radiation therapy and concurrent cisplatinum between May of 1988 and September of 1993 at our hospital. Radiation therapy consisted of external irradiation and 1-2 sessions of intracavitary irradiation, Cisplatinum was administered in bolus injection of 25mg/m 2 at weekly intervals during the course of external radiation therapy. Results : Of the 26 patients, twenty-five patients were evaluable for estimation of response. Median follow-up period was 25 months with ranges from 3 to 73 months. Stage IIB, III, and IVA were 16, 5,4 patients, respectively. Twenty patients were squamous cell carcinoma. Response was noted in all 25 patients: complete response(CR) in 17/25(68%), partial response(PR) in 8/25(32%). Of the 24 patients except one who died of sepsis at 3 months follow-up, seventeen patients(70.8%) maintained local control in the pelvis: 16/17(94.1%) in CR, 1/17(14.3%) in PR. Fourteen of the 17 patients with CR are alive disease free on the completion of follow-up. Median survival is 28 months for CR and 15 months for PR. Analysis of 5-year survival by stage shows 11/16(59.8) in IIB, 3/5(60.6%) in III, and 1/4(25.0%) in IVA. Overall 5-year survival rate was 55.2%. Ten Patients recurred: 4 at locoregional, 3 in distant metastasis and 3 with locoregional and distant site. Toxicity by addition of cisplatinum was not excessive. Conclusion : Although the result of this

  7. Recent advance on the antitumor and antioxidant activity of grape seed extracts

    Directory of Open Access Journals (Sweden)

    Zhu FM

    2015-05-01

    Full Text Available Fengmei Zhu, Bin Du, Jun Li College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, Hebei Province, People's Republic of China Abstract: The grape pomace (including seeds and stems poses potential disposal and pollution problems along with loss of valuable biomass and nutrients. The utilization of grape seeds processing as a source of functional ingredients is a promising field. Grape seed extract provides a concentrated source of polyphenols. Grape seed extract is known as an effective antioxidant that protects the body from premature aging and disease. A number of phytochemicals including resveratrol, proanthocyanidins, etc, have demonstrated significant benefits in cancer chemoprevention. In this review, we summarize the existing knowledge on the antitumor and antioxidant activity of grape seeds polyphenols. Keywords: grape seed, antitumor activity, antioxidant activity, polyphenol, proanthocyanidin

  8. Research Advances: Nanoscale Molecular Tweezers; Cinnamon as Pesticide?; Recently Identified Dietary Sources of Antioxidants

    Science.gov (United States)

    King, Angela G.

    2004-12-01

    This Report from Other Journals surveys articles of interest to chemists that have been recently published in other science journals. Topics surveyed include reports that receptors have been designed to act as molecular tweezers; cinnamon has potential in the fight against mosquitoes; and high levels of antioxidants are found in some surprising foods. See Featured Molecules .

  9. Phenolic profiling and therapeutic potential of local flora of Azad Kashmir; In vitro enzyme inhibition and antioxidant

    Directory of Open Access Journals (Sweden)

    Raza Muhammad Asam

    2017-12-01

    Full Text Available The current study supports the phytochemical screening, evaluation of antioxidant and enzyme inhibition potential and correlations between antioxidant activities and phenolics of Rumex dentatus (Family: Polygonaceae, Mentha spicata (Family: Lamiaceae, Withania somnifera (Family: Solanaceae, Nerium indicum (Family: Apocynaceae and Artemisia scoparia (Family: Asteraceae. The herbal materials were extracted in ethanol (90% and partitioned between several solvents based on polarities. Total phenols were determined with FC method and ranged 21.33 ± 1.53 - 355.67 ± 6.03 mg GAE/ mg of the extract. Antioxidant activities (DPPH, total iron reducing capacity, phosphomolybdate assay & FRAP and enzyme inhibition potential (Protease, AChE & BChE were performed by the standard protocols. The results showed that all extracts exhibited significant DPPH activity ranging from 12.67 ± 2.08 - 92.67 ± 1.53%. The extracts that were active in DPPH activity also potrayed marvelous FRAP, total iron reducing and phosphomolybdate values. Correlation studies of antioxidant activities and the content of phenolic compounds in plant materials exhibited positive correlation between them. The outcome of enzyme inhibition activity exhibited that about 80% of the fractions under surveillance plants intimated more than 50% inhibition. Isolation of bioactive compounds from these plants is in progress.

  10. 124I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact

    International Nuclear Information System (INIS)

    Freudenberg, L.S.; Jentzen, W.; Goerges, R.; Knust, J.; Bockisch, A.; Marlowe, R.J.

    2007-01-01

    Purpose: This study evaluated the impact of 124 I-positron emission tomography (PET) dosimetry on post-primary surgery therapy in radioiodine-naive patients with advanced differentiated thyroid cancer (DTC). Patients, material, methods: In each of 28 thyroidectomized patients with high-risk DTC (one or more of pT4, pN1 or pM1), we gave 23-50 MBq of 124 I as an oral capsule and performed PET dosimetry to calculate the individualized therapeutic 131 I activity that would, insofar as possible, achieve a radioiodine dose ≥ 100 Gy to all metastases without exceeding 2 Gy to the blood (a surrogate for bone marrow toxicity). We thus determined the absorbed lesion dose per GBq of administered 131 I activity (LDpA) based on serial PET (4, 24, 48, 72 and 96 h after oral 124 I intake) and PET/computed tomography (25 h after 124 I intake) and the critical blood activity (CBA) based on blood and whole-body radiation counting (2, 4, 24, 48, 72, 96 h after 124 I intake). We compared the dosimetry-based interventions with our standard empirical protocol. Results: 25 patients had a total of 126 iodine-positive metastases. 18 (72%) of the 25 had solely iodine-avid metastases, while seven (28%) had both iodine-avid and -non-avid metastases. In two patients (8%), none of the iodine-avid metastases could have been practically treated with a sufficient radiation dose. Relative to the empirical protocol, 124 I-PET dosimetry findings changed management in 7 (25%) patients, e. g. allowing application of activities >11 GBq 131 I. Further changes included implementation of hematological back-up in a patient found to be at risk of life-threatening marrow toxicity, and early multimodal therapy in 9 (32%) patients. Conclusion: 124 I-PET dosimetry is a useful routine procedure in advanced DTC and may allow safer or more effective radioiodine activities and earlier multimodal interventions than do standard empirical protocols. (orig.)

  11. The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach.

    Science.gov (United States)

    Salahuddin, Parveen; Rabbani, Gulam; Khan, Rizwan Hasan

    2014-09-01

    Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies have shown that glycation induces the formation of the β-sheet structure in β-amyloid protein, α-synuclein, transthyretin (TTR), copper-zinc superoxide dismutase 1 (Cu, Zn-SOD-1), and prion protein. Aggregation of the β-sheet structure in each case creates fibrillar structures, respectively causing Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, and prion disease. It has been suggested that oligomeric species of glycated α-synuclein and prion are more toxic than fibrils. This review focuses on the pathway of AGE formation, the synthesis of different types of AGE, and the molecular mechanisms by which glycation causes various types of neurodegenerative disease. It discusses several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic and naturally occurring inhibitors. Modulation of the AGE-RAGE axis is now considered promising in the prevention of neurodegenerative diseases. Additionally, the review covers several defense enzymes and proteins in the human body that are important anti-glycating systems acting to prevent the development of neurodegenerative diseases.

  12. Advances of stem cell based-therapeutic approaches for tendon repair

    Directory of Open Access Journals (Sweden)

    Lidi Liu

    2017-04-01

    The translational potential of this article: This paper reviews recent progress on stem cell-based therapeutic approaches for tendon repair, which highlights its translational potential and challenges.

  13. Recent advances in role of chromium and its antioxidant combinations in poultry nutrition: A review

    Directory of Open Access Journals (Sweden)

    Z. Haq

    2016-12-01

    Full Text Available Poultry is reared in open side houses in most of the tropical countries, which results in huge temperature variation in shed causing stress resulting in increased demand of antioxidant supplementation. Since cooling of poultry houses or environment control is very expensive, thus methods focused on nutritional modifications appears to be the much logical approach. Stress increases mineral and vitamin mobilization from tissues and their excretion. Effect of some minerals and vitamin supplements such as chromium (Cr and ascorbic acid to elevate the negative effects of environmental stress is well documented. Cr functions as an antioxidant and its deficiency are said to disrupt carbohydrate and protein metabolism. Cr has been utilized for weight gain, to improve feed conversion ratio, increase relative organ weight, muscle development, decrease cholesterol, increase high-density lipoprotein cholesterol, and improve nutrient digestion. Therefore, the present review discusses the beneficial aspects of Cr with its effect in different doses and antioxidant combinations to explore and promote its optimum utilization in poultry nutrition and production.

  14. Recent advances in role of chromium and its antioxidant combinations in poultry nutrition: A review

    Science.gov (United States)

    Haq, Z.; Jain, R. K.; Khan, N.; Dar, M. Y.; Ali, S.; Gupta, M.; Varun, T. K.

    2016-01-01

    Poultry is reared in open side houses in most of the tropical countries, which results in huge temperature variation in shed causing stress resulting in increased demand of antioxidant supplementation. Since cooling of poultry houses or environment control is very expensive, thus methods focused on nutritional modifications appears to be the much logical approach. Stress increases mineral and vitamin mobilization from tissues and their excretion. Effect of some minerals and vitamin supplements such as chromium (Cr) and ascorbic acid to elevate the negative effects of environmental stress is well documented. Cr functions as an antioxidant and its deficiency are said to disrupt carbohydrate and protein metabolism. Cr has been utilized for weight gain, to improve feed conversion ratio, increase relative organ weight, muscle development, decrease cholesterol, increase high-density lipoprotein cholesterol, and improve nutrient digestion. Therefore, the present review discusses the beneficial aspects of Cr with its effect in different doses and antioxidant combinations to explore and promote its optimum utilization in poultry nutrition and production. PMID:28096611

  15. Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies.

    Science.gov (United States)

    Mimeault, M; Hauke, R; Batra, S K

    2007-09-01

    Basic and clinical research accomplished during the last few years on embryonic, fetal, amniotic, umbilical cord blood, and adult stem cells has constituted a revolution in regenerative medicine and cancer therapies by providing the possibility of generating multiple therapeutically useful cell types. These new cells could be used for treating numerous genetic and degenerative disorders. Among them, age-related functional defects, hematopoietic and immune system disorders, heart failures, chronic liver injuries, diabetes, Parkinson's and Alzheimer's diseases, arthritis, and muscular, skin, lung, eye, and digestive disorders as well as aggressive and recurrent cancers could be successfully treated by stem cell-based therapies. This review focuses on the recent advancements in adult stem cell biology in normal and pathological conditions. We describe how these results have improved our understanding on critical and unique functions of these rare sub-populations of multipotent and undifferentiated cells with an unlimited self-renewal capacity and high plasticity. Finally, we discuss some major advances to translate the experimental models on ex vivo and in vivo expanded and/or differentiated stem cells into clinical applications for the development of novel cellular therapies aimed at repairing genetically altered or damaged tissues/organs in humans. A particular emphasis is made on the therapeutic potential of different tissue-resident adult stem cell types and their in vivo modulation for treating and curing specific pathological disorders.

  16. The effect of Nitrogen Mustard on the enzymatic antioxidant defense of rat brain tissue and the therapeutic value of proanthocyanidin.

    Science.gov (United States)

    Tekiner, Ayhan; Yucel, Dogan; Bayar, Mehmet Akif; Yucel, Orhan; Erdem, Yavuz; Karakaya, Jale

    2011-01-01

    Nitrogen Mustard (NM) is an alkylating agent that damages cellular nuclear DNA after penetrating tissue. This results in cytostatic, mutagenic and cytotoxic effects. We used biochemical analyses to investigate the effect of NM gas administered through the dermal and respiratory routes, on the brain cortex of rats and also tried to show whether the antioxidant Proanthocyanidin (PC) could decrease this effect. A total of 30 rats were randomized into three groups: Group I: Control group, Group II: NM group, and Group III: NM + PC group. The rats were sacrificed 3 days after NM gas exposure. A segment of the cortical tissue was prepared for biochemical analyses. Biochemical analyses of cortical neural tissue regarding the Enzymatic Antioxidant Defense against NM were performed. The results of these analyses implied that PC was effective for healing of cortical neural tissue. These findings imply that structural changes induced by mustard gas can be prevented and restored by proanthocyanidin treatment.

  17. The Attending Nurse Caring Model: integrating theory, evidence and advanced caring-healing therapeutics for transforming professional practice.

    Science.gov (United States)

    Watson, Jean; Foster, Roxie

    2003-05-01

    This paper presents a proposed model: The Attending Nursing Caring Model (ANCM) as an exemplar for advancing and transforming nursing practice within a reflective, theoretical and evidence-based context. Watson's theory of human caring is used as a guide for integrating theory, evidence and advanced therapeutics in the area of children's pain. The ANCM is offered as a programme for renewing the profession and its professional practices of caring-healing arts and science, during an era of decline, shortages, and crises in care, safety, and hospital and health reform. The ANCM elevates contemporary nursing's caring values, relationships, therapeutics and responsibilities to a higher/deeper order of caring science and professionalism, intersecting with other professions, while sustaining the finest of its heritage and traditions of healing.

  18. Fractionate analysis of the phytochemical composition and antioxidant activities in advanced breeding lines of high-lycopene tomatoes.

    Science.gov (United States)

    Ilahy, Riadh; Piro, Gabriella; Tlili, Imen; Riahi, Anissa; Sihem, Rabaoui; Ouerghi, Imen; Hdider, Chafik; Lenucci, Marcello Salvatore

    2016-01-01

    This study investigates the antioxidant components [lycopene, total phenolics, total flavonoids, ascorbic acid (AsA) and dehydroascorbic acid (DHA)] as well as antioxidant activities of the hydrophilic and lipophilic fractions (AAHF and AALF) of peel, pulp and seed fractions isolated from red-ripe berries of the ordinary tomato cultivar Rio Grande and the two high-lycopene tomato breeding lines HLT-F61 and HLT-F62 simultaneously grown in an open-field of Northern Tunisia. Significant differences (p tomato berries had the highest AsA content (345 mg per kg fw and 115 mg per kg fw, respectively), while no significant difference was found in the seed fraction between HLT-F62 and Rio Grande. The HLT-F62 pulp fraction showed the highest content of AsA (186 mg per kg fw) and DHA (151 mg per kg fw) among all the assayed cultivars. Except for the peel fraction, where HLT-F61 had similar AAHF values to HLT-F62, the high-lycopene line HLT-F61 showed higher AAHF values than HLT-F62 and Rio Grande. Regardless of the fraction, the highest AALF values were recorded in HLT-F61 berries. Thus, both HLT tomato lines are promising for the introduction, as advanced hybrids, in either fresh market or processing industry.

  19. Implications for Advanced Nursing Practice in the Use of Therapeutic Touch.

    Science.gov (United States)

    1993-01-01

    simple shoulder and back massage , combined with a few deep breaths, may facilitate relaxation. The practitioner may use physical touch during unruffling...the nursing community. Several authors use the term strictly in relation to comforting touch behaviors, such as hand holding and massage . 2...Therapeutic Touch 40 earlier extubations, and greater weight gain (Field, 1990). Babies respond well to Therapeutic Touch ; the key is use a gentle

  20. Antioxidant effect of aqueous extract of four plants with therapeutic potential on gynecological diseases; Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria.

    Science.gov (United States)

    Ji, Shaojian; Fattahi, Amir; Raffel, Nathalie; Hoffmann, Inge; Beckmann, Matthias W; Dittrich, Ralf; Schrauder, Michael

    2017-11-25

    Little information is available concerning antioxidant effects of plant teas (water boiled) which are used more commonly in traditional Chinese medicine than other extracts. Thus, we addressed this issue by evaluating the ability of teas from four different plants with therapeutic potential on gynecological diseases. The aqueous extracts of Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then their effects on copper-induced low-density lipoprotein cholesterol (LDL-C) oxidation were evaluated by spectrophotometric method. Density gradient ultracentrifugation method was recruited to isolate LDL-C from healthy individuals. Our results showed that adding 10, 20, and 30 µl S. persicae could increase the lag phase duration of LDL-C oxidation compared with control reaction 12, 21, and 33%, respectively. The most effective delay (87%) was observed when 30 µl H. diffusa was added to the reaction. In cases of L. cardiaca and C. zedoaria, we found no significant influence on the lag phase duration (p > 0.05). Moreover, our findings about starting point of the decomposition phase were almost in parallel with the lag phase results, as 30 µl of S. persicae or H. diffusa teas could significantly increase the initiation time of decomposition (p < 0.05). In conclusion our results showed that both S. persicae and H. diffusa teas and not L. cardiaca and C. zedoaria could have medicinal therapeutic effects partly through direct oxidation prevention.

  1. Long Term Therapeutic Efficacy of a Soft Monobloc Mandibular Advancement Device in Adults with Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Fabiana Ballanti

    2015-01-01

    Full Text Available Aim. To evaluate the long term (48 months therapeutic efficacy of a soft monobloc mandibular advancement device in adult patients with mild or moderate obstructive sleep apnea. Methods. The study population comprised 28 patients (6 female and 22 male, mean age 52.2±6.8 years affected by obstructive sleep apnea. After a baseline medical and somnographic examination, a functional examination of the stomatognathic system, and a questionnaire focused on sleep-related qualities and a daytime somnolence, each patient received an individual device. Two follow-ups were made 6 months (T1 and 48 months (T2 after soft monobloc mandibular advancement device treatment had been initiated, and all initial examinations were repeated. Results. The statistical analysis showed a significant decrease in body mass index value between T1 and T2 (ρ = 0,012, an increase of Epworth sleepiness scale value between T1 and T2 (ρ = 0,012, and a significant improvement and decrease of apnea/hypopnea index between T0 and T1 (ρ = 0,010 and between T0 and T2 (ρ = 0,013. Conclusion. Treatment with the soft monobloc mandibular advancement device is a therapeutic solution with long term and stable effects (48 months for patients suffering from mild or moderate obstructive sleep apnea.

  2. Recent advances in therapeutic recruitment of mammalian RNAi and bacterial CRISPR-Cas DNA interference pathways as emerging antiviral strategies.

    Science.gov (United States)

    Chin, Wei-Xin; Ang, Swee Kim; Chu, Justin Jang Hann

    2017-01-01

    In invertebrate eukaryotes and prokaryotes, respectively, the RNAi and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) pathways are highly specific and efficient RNA and DNA interference systems, and are well characterised as potent antiviral systems. It has become possible to recruit or reconstitute these pathways in mammalian cells, where they can be directed against desired host or viral targets. The RNAi and CRISPR-Cas systems can therefore yield ideal antiviral therapeutics, capable of specific and efficient viral inhibition with minimal off-target effects, but development of such therapeutics can be slow. This review covers recent advances made towards developing RNAi or CRISPR-Cas strategies for clinical use. These studies address the delivery, toxicity or target design issues that typically plague the in vivo or clinical use of these technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The positive clinical therapeutically effects of Escin on advanced thyroid cancer

    OpenAIRE

    Mei, Jin?Yu; Zhang, Ming?Jun; Wang, Yuan?Yuan; Liu, Ye?Hai

    2017-01-01

    Abstract The incidences of thyroid cancer keep rising worldwide over the past few decades. Although most thyroid cancers are indolent and highly curable, the treatment for advanced thyroid cancer remains challengeable in clinical practice. We performed two separate cohorts to evaluate the safety and efficiency of Escin in patients with advanced thyroid cancer . In cohort 1, 120 patients were divided into four groups equally and were administrated with placebo or different dosages of Escin. Th...

  4. Advancing the Interdisciplinary Collaborative Health Team Model: Applying Democratic Professionalism, Implementation Science, and Therapeutic Alliance to Enact Social Justice Practice.

    Science.gov (United States)

    Murphy, Nancy

    2015-01-01

    This essay reframes the interdisciplinary collaborative health team model by proposing the application of 3 foundational pillars-democratic professionalism, implementation science, and therapeutic alliance to advance this practice. The aim was to address challenges to the model, enhance their functional capacity, and explicate and enact social justice practices to affect individual health outcomes while simultaneously addressing health inequities. The pillars are described and examples from the author's dissertation research illustrate how the pillars were used to bring about action. Related theories, models, and frameworks that have negotiation, capacity building, collaboration, and knowledge/task/power sharing as central concepts are presented under each of the pillars.

  5. Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics.

    Science.gov (United States)

    McArthur, Monica A

    2017-06-13

    Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV.

  6. Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics

    Science.gov (United States)

    McArthur, Monica A.

    2017-01-01

    Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV. PMID:28608813

  7. Advanced new strategies for metastatic cancer treatment by therapeutic stem cells and oncolytic virotherapy

    OpenAIRE

    Park, Geon-Tae; Choi, Kyung-Chul

    2016-01-01

    The field of therapeutic stem cell and oncolytic virotherapy for cancer treatment has rapidly expanded over the past decade. Oncolytic viruses constitute a promising new class of anticancer agent because of their ability to selectively infect and destroy tumor cells. Engineering of viruses to express anticancer genes and specific cancer targeting molecules has led to the use of these systems as a novel platform of metastatic cancer therapy. In addition, stem cells have a cancer specific migra...

  8. Palliative care as a primary therapeutic approach in advanced dementia: a narrative review.

    Science.gov (United States)

    Zahradnik, Erin K; Grossman, Hillel

    2014-11-01

    The goal of this narrative review was to identify and summarize the ways in which palliative care could benefit patients who have advanced dementia. This case-based discussion article examines current literature on palliative care for dementia. Dementia is an incurable, progressive disease that affects millions of subjects. The prevalence has grown in the last decade and is projected to continue on this trajectory. In the later stages of dementia, subjects require increasing levels of care due to severe cognitive and functional impairment. Although the field of palliative medicine focuses on improving the quality of life of patients with life-limiting illnesses, many patients with advanced dementia do not receive palliative care services. Palliative care has been shown to improve patient and caregiver satisfaction, quality of life, and symptom burden at the end of life. Patients with advanced dementia would benefit from increased access to palliative care. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  9. Advanced Heart Failure Therapies for Cancer Therapeutics-Related Cardiac Dysfunction.

    Science.gov (United States)

    Bianco, Christopher M; Al-Kindi, Sadeer G; Oliveira, Guilherme H

    2017-04-01

    End-stage heart failure in cancer survivors may result from cardiotoxic chemotherapy and/or chest radiation and require advanced therapies, including left ventricular assist devices (LVADs) and transplantation. Traditionally, such therapies have been underutilized in cancer survivors owing to lack of experience and perceived risk of cancer recurrence. Recent data from large registries, however, have shown excellent outcomes of LVADs and transplantation in cancer survivors, albeit subject to careful selection and special considerations. This article summarizes all aspects of advanced heart failure therapies in patients with cancer therapy-related cardiac dysfunction and underscores the need for careful selection of these candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The positive clinical therapeutically effects of Escin on advanced thyroid cancer.

    Science.gov (United States)

    Mei, Jin-Yu; Zhang, Ming-Jun; Wang, Yuan-Yuan; Liu, Ye-Hai

    2017-05-01

    The incidences of thyroid cancer keep rising worldwide over the past few decades. Although most thyroid cancers are indolent and highly curable, the treatment for advanced thyroid cancer remains challengeable in clinical practice. We performed two separate cohorts to evaluate the safety and efficiency of Escin in patients with advanced thyroid cancer . In cohort 1, 120 patients were divided into four groups equally and were administrated with placebo or different dosages of Escin. The pharmacokinetics of Escin and the side effects were evaluated. In cohort 2, 120 patients were treated with Escin. Several biomarkers related to the progression of thyroid cancer were evaluated. Kaplan-Meier (KM) analyses were performed to evaluate progression-free survival (PFS) and overall survival (OS). The serum Escin concentrations were stable during the treatment. Escin (0.6 mg/kg/day for 9 days, intravenous injection) was tolerable for patients with thyroid cancer . Escin significantly reduced the serum levels of TSH, TgAb, Tg, and calcitonin and prolonged the PFS and OS for patients with advanced thyroid cancer. This study showed Escin is efficient and well tolerated in patients with advanced thyroid cancer. Future studies are needed to investigate the mechanism of Escin on thyroid cancer and the proper dosage of Escin clinically. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. Cross-Disciplinary Medical Advances with Neuroengineering: Challenges Spur Development of Unique Rehabilitative and Therapeutic Interventions.

    Science.gov (United States)

    Elbasiouny, Sherif

    2017-01-01

    Neuroengineering brings tools and techniques from the engineering fields into neuroscience to create new approaches for investigating the central nervous system (CNS). This fusion of disciplines is advancing our knowledge of how the CNS works and how we can enhance our natural cognitive and emotional function and restore neurological functions that are compromised by disease or injury.

  12. Promising anti-oxidative therapeutic potentials of edible freshwater snail Bellamya bengalensis extract against arsenic-induced rat hepatic tissue and DNA damage

    Directory of Open Access Journals (Sweden)

    Sk Sajed Ali

    2016-09-01

    Full Text Available Epidemiological data suggest that arsenic ultimately results in cancer in different parts of the body. Several synthetic therapeutic agents manifest inadequate potency with severe side effects against arsenic toxicity. The flesh of B. bengalensis, has long been used as an ethno-medicine in case of arthritis, blood-impurities, impaired immune system, conjunctivitis and liver anomalies. This potent organism might be a natural choice against arsenic and several other toxicities. Our earlier studies on arsenic-exposed human can correlate carcinogenesis with DNA-damage. In an attempt to investigate the possible protective and therapeutic effect against arsenic induced hepatotoxicity, the extract of B. bengalensis was tested in arsenic intoxicated rat model. The time- and dose-dependent effect of arsenic toxicity was also tested in B. bengalensis. Sodium-meta-arsenite NaAsO2 (0.6 ppm/100g bw/day for 28 days, as earlier reported was treated alone or in combination with the B. bengalensis water extract (BBE, 100 mg/100g bw to rat and compared with vehicle treated control. In a separate experiment, the B. bengalensis was exposed to high concentration of NaAsO2 contaminated water (5 to 20 ppm for 1 to 9 days in laboratory condition and their DNA quality was evaluated in relation to its possible oxidative threat. Any concentration of arsenic was incapable to initiate a significant DNA damage in B. bengalensis. Lipid peroxidation was increased in arsenic exposed B. bengalensis after longer duration of its exposure. Increase in reduced antioxidant like non-protein-soluble thiol (NPSH is concordant with the decrease in lipid peroxidation and DNA stability in this organism. In rat experiment, the BBE supplementation strongly prevented arsenic-induced oxidative, necrotic and apoptotic damages to liver tissue/DNA by strengthening antioxidant systems, which has been shown in hepatic DNA-fragmentation, comet-assay, histo-architecture (hematoxylin/eosin, alkaline

  13. Monitoring the therapeutic response of locally advanced breast cancer patients: sequential in vivo proton MR spectroscopy study.

    Science.gov (United States)

    Kumar, Mahesh; Jagannathan, N R; Seenu, V; Dwivedi, S N; Julka, P K; Rath, G K

    2006-08-01

    To evaluate the use of the water-to-fat (W-F) value obtained from in vivo proton ((1)H) MR spectroscopy (MRS) as a response indicator of cytologically confirmed patients with locally advanced breast cancer (LABC), and to monitor the therapeutic response of such patients to neoadjuvant chemotherapy (NACT). Serial (1)H MR spectra were recorded both before and after the completion of chemotherapy in 33 LABC patients (with infiltrating ductal carcinoma (IDC)) at 1.5T. In addition, spectra from normal breast tissues of 28 healthy volunteers were recorded. Malignant breast tissues showed elevated W-F values compared to normal breast tissues of controls. Statistically significant higher pretherapy W-F value (P W-F value showed a decrease that was statistically significant (P W-F value had no correlation with the menstrual status of the patients. A comparison of pretherapy W-F value with pretherapy tumor volume showed a fair correlation (P = 0.05), while the posttherapy W-F value showed no such correlation with the posttherapy tumor volume. This study demonstrates that simple, conventional in vivo (1)H MRS is a useful technique for monitoring the therapeutic response of breast cancer patients. The observed trend in the reduction of W-F value provides a noninvasive response indicator to monitor the clinical outcome of locally advanced breast cancer patients to NACT.

  14. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches.

    Science.gov (United States)

    Boxer, Adam L; Yu, Jin-Tai; Golbe, Lawrence I; Litvan, Irene; Lang, Anthony E; Höglinger, Günter U

    2017-07-01

    Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms that are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future. These criteria also include definitions for variant PSP syndromes with different patterns of movement, language, or behavioural features than have been conclusively associated with PSP pathology. Data from new diagnostic biomarkers can be combined with the clinical features of disease to increase the specificity of the new criteria for underlying PSP pathology. Because PSP is associated with tau protein abnormalities, there is growing interest in clinical trials of new tau-directed therapies. These therapies are hypothesised to have disease-modifying effects by reducing the concentration of toxic forms of tau in the brain or by compensating for loss of tau function. Since tau pathology is also central to Alzheimer's disease and chronic traumatic encephalopathy, a successful tau therapeutic for PSP might inform treatment of other neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Advances in Virus-Directed Therapeutics against Epstein-Barr Virus-Associated Malignancies

    Directory of Open Access Journals (Sweden)

    Sajal K. Ghosh

    2012-01-01

    Full Text Available Epstein-Barr virus (EBV is the causal agent in the etiology of Burkitt’s lymphoma and nasopharyngeal carcinoma and is also associated with multiple human malignancies, including Hodgkin’s and non-Hodgkin’s lymphoma, and posttransplantation lymphoproliferative disease, as well as sporadic cancers of other tissues. A causal relationship of EBV to these latter malignancies remains controversial, although the episomic EBV genome in most of these cancers is clonal, suggesting infection very early in the development of the tumor and a possible role for EBV in the genesis of these diseases. Furthermore, the prognosis of these tumors is invariably poor when EBV is present, compared to their EBV-negative counterparts. The physical presence of EBV in these tumors represents a potential “tumor-specific” target for therapeutic approaches. While treatment options for other types of herpesvirus infections have evolved and improved over the last two decades, however, therapies directed at EBV have lagged. A major constraint to pharmacological intervention is the shift from lytic infection to a latent pattern of gene expression, which persists in those tumors associated with the virus. In this paper we provide a brief account of new virus-targeted therapeutic approaches against EBV-associated malignancies.

  16. Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed.

    Science.gov (United States)

    Ando, Hidenori; Kobayashi, Sakiko; Abu Lila, Amr S; Eldin, Noha Essam; Kato, Chihiro; Shimizu, Taro; Ukawa, Masami; Kawazoe, Kazuyoshi; Ishida, Tatsuhiro

    2015-12-28

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the "fluid" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    So Yeon Kim

    2015-11-01

    Full Text Available Hypoxia-inducible factor (HIF prolyl hydroxylases (PHDs are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.

  18. Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics.

    Science.gov (United States)

    Pokorny, Jan; Borkova, Lucie; Urban, Milan

    2018-02-13

    Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. [Advanced luminal breast cancer (hormone receptor-positive, HER2 negative): New therapeutic options in 2015].

    Science.gov (United States)

    Vanacker, Hélène; Bally, Olivia; Kassem, Loay; Tredan, Olivier; Heudel, Pierre; Bachelot, Thomas

    2015-06-01

    Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

  20. Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Pasqualucci, Daniele; Fornaro, Alessandra; Castelli, Gabriele; Rossi, Alessandra; Arretini, Anna; Chiriatti, Chiara; Targetti, Mattia; Girolami, Francesca; Corda, Marco; Orrù, Pierpaolo; Matta, Gildo; Stefàno, Pierluigi; Cecchi, Franco; Porcu, Maurizio; Olivotto, Iacopo

    2015-11-01

    The clinical course of patients with hypertrophic cardiomyopathy and advanced heart failure (HF) subtended by progressive left ventricular dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator and heart transplantation (HT) in patients with hypertrophic cardiomyopathy evaluated at 2 Italian referral centers >3 decades. All-cause mortality and a combined end point including death, HT, or appropriate implantable cardioverter-defibrillator shock were assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire hypertrophic cardiomyopathy cohort) followed up for 6.1±6.9 years after development of New York Heart Association class III to IV symptoms. At enrollment, left ventricular ejection fraction was 50% in 16; all had restrictive left ventricular filling. During follow-up, 35 patients died (49%%; 5-year rate, 49%) and 53 met the combined end point (75%; 5-year rate, 62%). Most events occurred in the 3 years after HF onset (17% per year compared with only 3% per year subsequently). Appropriate implantable cardioverter-defibrillator shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed, and 13 excluded; 2 early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. In hypertrophic cardiomyopathy, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first 3 years after onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favorable but requires early consideration, as the window of opportunity may be short. © 2015 American Heart Association, Inc.

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

    Directory of Open Access Journals (Sweden)

    S S Agarwal

    2015-01-01

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

  2. How are we improving the delivery to back of the eye? Advances and challenges of novel therapeutic approaches.

    Science.gov (United States)

    Agrahari, Vibhuti; Agrahari, Vivek; Mandal, Abhirup; Pal, Dhananjay; Mitra, Ashim K

    2017-10-01

    Drug delivery to the back of the eye requires strategic approaches that guarantee the long-term therapeutic effect with patient compliance. Current treatments for posterior eye diseases suffer from significant challenges including frequent intraocular injections of anti-VEGF agents and related adverse effects in addition to the high cost of the therapy. Areas covered: Treatment challenges and promising drug delivery approaches for posterior segment eye diseases, such as age-related macular degeneration (AMD) are summarized. Advances in the development of several nanotechnology-based systems, including stimuli-responsive approaches to enhance drug bioavailability and overcome existing barriers for effective ocular delivery are discussed. Stem cell transplantation and encapsulated cell technology (ECT) approaches to treat posterior eye diseases are elaborated. Expert opinion: There are several drug delivery systems demonstrating promising results. However, a better understanding of ocular barriers, disease pathophysiology, and drug clearance mechanisms is required for better therapeutic outcomes. The stem cell transplantation strategy and ECT approach provide positive results in AMD therapy, but there are a number of challenges that must be overcome for long-term efficiency. Ultimately, there are numerous multidimensional challenges to cure vision problems and a collaborative approach among scientists is required.

  3. Therapeutic benefits and tolerance of chemoradiotherapy for advanced and recurrent head and neck cancers

    International Nuclear Information System (INIS)

    Nishio, Masamichi; Myoujin, Miyako; Kawashima, Kazuyuki; Mizoguchi, Fumiki; Onimaru, Rikiya; Tanaka, Katsuhiko; Asano, Katsushi; Somekawa, Yukihiro

    1999-01-01

    Results of chemoradiation therapy for head and neck cancers that were locally advanced or recurrent or both were investigated retrospectively. From 1983 thorough 1995, 136 patients were treated with radiotherapy and with multiagent chemotherapy including cisplatin. Forty-two patients were treated first with chemoradiation, then with high-dose cisplatin every 4 to 6 weeks. Sixty-seven patients with recurrent cancers were treated with high-dose cisplatin. Twenty-seven patients with previously untreated cancers received chemoradiation and four medium doses of cisplatin a week every 4 weeks. Primary response rates were 88% in patients with previously untreated cancers who received high-dose cisplatin, 34% in patients with recurrent cancers who received high-dose cisplatin, and 100% in patients with previously untreated cancers who received medium-dose cisplatin. Treatment with high-dose cisplatin was more often of longer duration or was not completed than was treatment with medium-dose cisplatin because of more severe side effects. Chemoradiotherapy with a fractionated, medium dose of cisplatin was well tolerated and achieved good results. (author)

  4. Advances in analytical methodologies to guide bioprocess engineering for bio-therapeutics.

    Science.gov (United States)

    Saldova, Radka; Kilcoyne, Michelle; Stöckmann, Henning; Millán Martín, Silvia; Lewis, Amanda M; Tuite, Catherine M E; Gerlach, Jared Q; Le Berre, Marie; Borys, Michael C; Li, Zheng Jian; Abu-Absi, Nicholas R; Leister, Kirk; Joshi, Lokesh; Rudd, Pauline M

    2017-03-01

    This study was performed to monitor the glycoform distribution of a recombinant antibody fusion protein expressed in CHO cells over the course of fed-batch bioreactor runs using high-throughput methods to accurately determine the glycosylation status of the cell culture and its product. Three different bioreactors running similar conditions were analysed at the same five time-points using the advanced methods described here. N-glycans from cell and secreted glycoproteins from CHO cells were analysed by HILIC-UPLC and MS, and the total glycosylation (both N- and O-linked glycans) secreted from the CHO cells were analysed by lectin microarrays. Cell glycoproteins contained mostly high mannose type N-linked glycans with some complex glycans; sialic acid was α-(2,3)-linked, galactose β-(1,4)-linked, with core fucose. Glycans attached to secreted glycoproteins were mostly complex with sialic acid α-(2,3)-linked, galactose β-(1,4)-linked, with mostly core fucose. There were no significant differences noted among the bioreactors in either the cell pellets or supernatants using the HILIC-UPLC method and only minor differences at the early time-points of days 1 and 3 by the lectin microarray method. In comparing different time-points, significant decreases in sialylation and branching with time were observed for glycans attached to both cell and secreted glycoproteins. Additionally, there was a significant decrease over time in high mannose type N-glycans from the cell glycoproteins. A combination of the complementary methods HILIC-UPLC and lectin microarrays could provide a powerful and rapid HTP profiling tool capable of yielding qualitative and quantitative data for a defined biopharmaceutical process, which would allow valuable near 'real-time' monitoring of the biopharmaceutical product. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Antioxidants inhibit advanced glycosylation end-product-induced apoptosis by downregulation of miR-223 in human adipose tissue-derived stem cells

    Science.gov (United States)

    Wang, Zhe; Li, Hongqiu; Guo, Ran; Wang, Qiushi; Zhang, Dianbao

    2016-01-01

    Advanced glycosylation end products (AGEs) are endogenous inflammatory mediators that induce apoptosis of mesenchymal stem cells. A potential mechanism includes increased generation of reactive oxygen species (ROS). MicroRNA-223 (miR-223) is implicated in the regulation of cell growth and apoptosis in several cell types. Here, we tested the hypothesis that antioxidants N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) inhibit AGE-induced apoptosis via a microRNA-dependent mechanism in human adipose tissue-derived stem cells (ADSCs). Results showed that AGE-HSA enhanced apoptosis and caspase-3 activity in ADSCs. AGE-HSA also increased ROS generation and upregulated the expression of miR-223. Interestingly, reductions in ROS generation and apoptosis, and upregulation of miR-223 were found in ADSCs treated with antioxidants NAC and AAP. Furthermore, miR-223 mimics blocked antioxidant inhibition of AGE-induced apoptosis and ROS generation. Knockdown of miR-223 amplified the protective effects of antioxidants on apoptosis induced by AGE-HSA. miR-223 acted by targeting fibroblast growth factor receptor 2. These results indicate that NAC and AAP suppress AGE-HSA-induced apoptosis of ADSCs, possibly through downregulation of miR-223. PMID:26964642

  6. Therapeutic application of 99Tc-MDP in advanced nodose rheumatoid patients with multiple arthrosis erosion and malfunctioning

    International Nuclear Information System (INIS)

    Yuan Jiming

    2001-01-01

    Objective: To evaluate clinical effect of 99 Tc-MDP in treating arthrosis erosion in advanced nodose rheumatism. Methods: Therapy was performed undisrupted for 1 to 2 years in each patient at a high dose of 1.0-1.5 g/month. Results: After more than 1 year's 99 Tc-MDP therapy, 10 patients with multiple arthrosis erosion and serious malfunctioning had function recovery and arthral reformation of different extent. Patients with obvious therapeutic effects were able to walk, travel and completely or partially took care of themselves. Cortisone was prohibited or permitted at a lower dose of 1.25 mg/day in 3 patients who were dependant on prednisone. As results from 99 Tc-MDP therapy, X-ray photography revealed broadened arthral gap, reformation of previously eroded arthrosis and even improvement in osteoporosis. Conclusion: Reversible changes resulted from 99 Tc-MDP therapy showed breakthrough in treatment of advanced nodose rheumatism and serious ostearthritis, whose pathological changes were previously considered irreversible

  7. Integration of novel therapeutics into combined modality therapy of locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Gandara, David; Narayan, Samir; Lara, Primo N; Goldberg, Zelanna; Davies, Angela; Lau, Derrick H M; Mack, Philip; Gumerlock, Paul; Vijayakumar, Srinivasan

    2005-07-01

    Novel therapeutic agents (NTA) directed against a wide array of newly described molecular targets are now entering clinical investigation, many in the treatment of non-small cell lung cancer (NSCLC). The great majority of these clinical trials have been directed toward patients with advanced stage (metastatic) disease. More recently, study of NTAs has turned toward earlier-stage disease. Locally advanced, or stage III, NSCLC represents a large and heterogeneous group of patients and several clinically distinct substages. During the last 15 years, randomized clinical trials have shown improved survival with sequential chemoradiation compared with radiation alone and, more recently, the superiority of concurrent versus sequential chemoradiation. As NTAs have increasingly shown clinical activity against NSCLC, questions of how to incorporate them into clinical trials in stage III disease, whether they should be given together with radiotherapy, substituting for chemotherapy, or whether they should be added to current chemoradiation strategies, all remain as issues. Here, we describe conceptual issues, preclinical rationale, and ongoing or planned clinical trials incorporating NTAs into current treatment paradigms for unresectable stage III NSCLC.

  8. Nanotechnological advances for cutaneous release of tretinoin: an approach to minimize side effects and improve therapeutic efficacy.

    Science.gov (United States)

    Raminelli, Ana Claudia Pompeu; Romero, Valeria; Semreen, Mohammad H; Leonardi, Gislaine Ricci

    2018-03-12

    The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Herein we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction.

    Science.gov (United States)

    Natsume, Osamu; Ohya, Yukihiro

    2018-01-01

    Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  10. Variability in the therapeutic management of advanced ovarian cancer patients: a five-country survey of oncologists

    Directory of Open Access Journals (Sweden)

    Audibert C

    2017-12-01

    Full Text Available Céline Audibert,1 Anna Perlaky,2 Mark Stuntz,2 Daniel Glass2 1Deerfield Institute, Epalinges, Switzerland; 2Deerfield Institute, New York, NY, USA Background: Advanced ovarian cancer patients have a poor prognosis, mainly because the disease is diagnosed at a late stage. A number of therapeutic approaches, such as neoadjuvant and maintenance therapies, have been developed to try to improve treatment outcome. In parallel, the targeted therapies bevacizumab and olaparib have recently been approved for ovarian cancer treatment. The goal of our survey was to provide a comprehensive, global depiction of advanced ovarian cancer treatments across different regions.Patients and methods: Oncologists from France, Italy, Germany, the UK, and the USA were invited to participate in an online survey. Participants were eligible if they personally managed at least 15 ovarian cancer patients. Quantitative questions addressed the proportion of patients in neoadjuvant, treatment, and maintenance settings; proportion of BRCA-positive patients; and the type of treatment prescribed per setting and per line of therapy, depending on the patient’s BRCA status.Results: A total of 138 respondents completed our survey in Europe and 132 in the USA. The proportions of patients in treatment, maintenance, and remission were identical across each country and line of treatment at 60%, 20%, and 20%, respectively. The proportion of BRCA-tested patients ranged from 45% in Italy to 73% in the USA, with 10% (UK–21% (Italy of tested patients having a positive status. Levels of bevacizumab and olaparib prescriptions differed based on the country, line of treatment, and setting, with a significant share of patients receiving both drugs outside of their approved indications for ovarian cancer treatment.Conclusion: This survey provides real-world data on how advanced ovarian cancer patients are currently treated: 1 BRCA testing was not performed systematically, which raises concerns

  11. Antioxidant supplements for liver diseases

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2011-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal.......Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  12. Advances in Therapeutic Fc Engineering - Modulation of IgG-Associated Effector Functions and Serum Half-life.

    Science.gov (United States)

    Saxena, Abhishek; Wu, Donghui

    2016-01-01

    Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation. The Fc region can further improve mAbs' efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cell-mediated phagocytosis. Moreover, Fc is the region interacting with the neonatal Fc receptor in a pH-dependent manner that can slow down IgG's degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anticancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce the cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering-based mAbs under clinical trials.

  13. Advances in therapeutic Fc engineering - modulation of IgG associated effector functions and serum half-life

    Directory of Open Access Journals (Sweden)

    Abhishek Saxena

    2016-12-01

    Full Text Available Today monoclonal immunoglobulin gamma (IgG antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs are achieved through both its antigen binding fragment (Fab and crystallizable fragment (Fc. Fab can specifically recognize tumor associated antigen (TAA and thus modulate TAA-linked downstream signaling pathways that may lead to inhibition of tumor growth, induction of tumor apoptosis and differentiation. The Fc region can further improve mAbs’ efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity (ADCC, complement-dependent cytotoxicity (CDC and antibody dependent cell-mediated phagocytosis (ADCP. Moreover, Fc is the region interacting with the neonatal Fc receptor (FcRn in a pH-dependent manner that can slow down IgG’s degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anti-cancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering based mAbs under clinical trials.

  14. Clinical observation and therapeutic evaluation of Rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer.

    Science.gov (United States)

    Deng, Wen-Ying; Song, Tao; Li, Ning; Luo, Su-Xia; Li, Xiang

    2014-01-01

    To observe the curative effects of rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer and analyze the correlation of CT perfusion (CTP) parameters and the expression of vascular endothelial growth factor (VEGF). Twenty patients with esophageal cancer confirmed pathologically were randomly divided into combined treatment (rh-endostatin+DP regimen) group and single chemotherapy group, 10 patients in each group, respectively. All patients were given conventional CT examination and CTP imaging for primary tumor. The level of VEGF, the size of tumor and CTP parameters (BF, BV, PS and MTT) before treatment and after 2 cycles of treatment were determined for the comparison and the correlation between CTP parameters and VEGF expression was analyzed. the therapeutic effect of rh-endostatin+DP regimen group was superior to single chemotherapy group. VEGF level after treatment in rh- endostatin +DP regimen group was obviously lower than single chemotherapy group (Prh-endostatin +DP regimen group, BF, BV and PS decreased while MTT increased after treatment (P0.05). Rh-endostatin can down-regulate the expression of VEGF in esophageal cancer, change the state of hypertransfusion and high permeability of tumor vessels and had the better curative effect and slighter adverse reactions when combined with chemotherapy.

  15. Antioxidant properties of flavonoids

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    Sofna D.S. Banjarnahor

    2015-01-01

    Full Text Available Flavonoids represent a remarkable group of plant secondary metabolites and have long been used as traditional medicines with scientifically proven pharmacological benefits. They serve vast-ranging medicinal activities that may lead drug discovery with novel and potential therapeutic evidence. Latest research magnifies primarily functional activity of flavonoids as antioxidant against oxidative stress. This review enlightens the prospective role of flavonoids as antioxidant.

  16. Facile-one pot-green synthesis, antibacterial, antifungal, antioxidant and antiplatelet activities of lignin capped silver nanoparticles: A promising therapeutic agent.

    Science.gov (United States)

    Marulasiddeshwara, M B; Dakshayani, S S; Sharath Kumar, M N; Chethana, R; Raghavendra Kumar, P; Devaraja, S

    2017-12-01

    The current work portrays the green synthesis of Lignin Capped Silver Nanoparticles (LCSN) and their antibacterial, antifungal, antioxidant and antiplatelet potential. The LCSN was synthesized in water using a carbohydrate based polymer 'lignin' as the reducing and capping agents. The peak at 406nm (λ max ) in the UV-Vis., spectrum and EDX analysis confirmed 1.68% (w/w) of silver was found to be loaded on lignin. The characteristic sharp peaks appeared in the PXRD spectrum showed fcc crystalline structure LCSN. SEM and TEM images indicated that the spherical Ag-NPs were well dispersed on lignin with an average particle size of ~10-15nm. LCSN showed antibacterial and antifungal activity against human pathogens S. aureus, E. coli and A. niger and the percentage of zone of inhibition was found to be 10%, 12% and 80% respectively. Further, LCSN was evaluated for antioxidant potential using DPPH scavenging assay, interestingly it showed antioxidant activity and the percentage against positive control vitamin C was found to be 70%. Furthermore, LCSN did not interfere in plasma coagulation; however, it found to inhibit agonist ADP induced platelet aggregation of human platelet rich plasma. The observed inhibition was found to be 37% and the calculated IC50 value was found to be 9mg/mL. LCSN did not lyses RBC membrane when assayed hemolytic activity suggesting its non-toxic nature. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Measuring the influence of a mental health training module on the therapeutic optimism of advanced nurse practitioner students in the United Kingdom.

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    Hemingway, Steve; Rogers, Melanie; Elsom, Stephen

    2014-03-01

    To evaluate the influence of a mental health training module on the therapeutic optimism of advanced nurse practitioner (ANP) students in primary care (family practice). Three cohorts of ANPs who undertook a Mental Health Problems in Primary Care Module as part of their MSc ANP (primary care) run by the University of Huddersfield completed the Elsom Therapeutic Optimism Scale (ETOS), in a pre- and postformat. The ETOS is a 10-item, self-administered scale, which has been used to evaluate therapeutic optimism previously in mental health professionals. All three cohorts who completed the scale showed an improvement in their therapeutic optimism scores. With stigma having such a detrimental effect for people diagnosed with a mental health problem, ANPs who are more mental health literate facilitated by education and training in turn facilitates them to have the skills and confidence to engage and inspire hope for the person diagnosed with mental health problems. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

  18. Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate

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    Ahmad Majzoub

    2018-03-01

    Conclusion: Antioxidants generally have a favourable effect on male fertility. Further studies are needed to identify the optimal antioxidant regimen that can be used safely and efficiently in clinical practice.

  19. The Therapeutic Potential of Resistant Starch in Modulation of Insulin Resistance, Endotoxemia, Oxidative Stress and Antioxidant Biomarkers in Women with Type 2 Diabetes: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Karimi, P; Farhangi, M Abbasalizad; Sarmadi, B; Gargari, B P; Zare Javid, A; Pouraghaei, M; Dehghan, P

    2016-01-01

    This trial aims to determine the effects of resistant starch (RS) subtype 2 (RS2) on glycemic status, metabolic endotoxemia and markers of oxidative stress. A randomized, controlled, parallel-group clinical trial group of 56 females with type 2 diabetes mellitus (T2DM) was divided to 2 groups. The intervention group (n = 28) and control group (n = 28) received 10 g/day RS2 or placebo for 8 weeks, respectively. Fasting blood samples were taken to determine glycemic status, endotoxin, high sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), antioxidant enzymes concentrations as well as uric acid at baseline and after the intervention. After 8 weeks, RS2 caused a significant decrease in the levels of MDA (-34.10%), glycosylated hemoglobin (-9.40%), insulin (-29.36%), homeostasis model of insulin resistance (-32.85%) and endotoxin (-25.00%), a significant increase in TAC (18.10%) and glutathione peroxidase (11.60%) as compared with control. No significant changes were observed in fasting plasma glucose, quantitative insulin sensitivity check index, hs-CRP, superoxide dismutase, catalase and uric acid in the RS2 group as compared with the control group. Supplementation with RS2 may be improved glycemic status, endotoxemia and markers of oxidative stress in patients with T2DM. © 2015 S. Karger AG, Basel.

  20. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

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    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  1. Recent Advancements in Targeted Delivery of Therapeutic Molecules in Neurodegenerative Disease–-Spinocerebellar Ataxia–-Opportunities and Challenges

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    Satya Prakash

    2008-01-01

    Full Text Available Drug discovery and its methodologies have been very effective in terms of treating cancers and immunological disorders but have not been able to stop genetic diseases as most of the drugs target at the protein level. They merely mitigate the symptoms of the disease. Spinocerebellar ataxia is a neurological genetic disorder that is caused by the formation of an abnormal protein. There have been several reports on ataxic drug development but actual clinical treatment is yet to be achieved. Oligonucleotide therapy called sequence specific siRNA mediated gene silencing has evolved with promising results. This approach emphasizes on suppressing the expression of the diseased gene at mRNA level. However, there is a limitation in delivery of siRNA to the target site. Several methods have been developed over the last decade to enhance the target specific delivery of DNA, siRNA, protein and small drug molecules for therapeutic purpose with less or no side effects. This review discusses the latest upcoming technologies in the field that focus on a number of nonviral nanocarriers for targeted delivery. In this review, we explore the promise and potential of novel therapeutics with interest on ataxia therapy.

  2. Reproductive cloning in humans and therapeutic cloning in primates: is the ethical debate catching up with the recent scientific advances?

    Science.gov (United States)

    Camporesi, S; Bortolotti, L

    2008-09-01

    After years of failure, in November 2007 primate embryonic stem cells were derived by somatic cellular nuclear transfer, also known as therapeutic cloning. The first embryo transfer for human reproductive cloning purposes was also attempted in 2006, albeit with negative results. These two events force us to think carefully about the possibility of human cloning which is now much closer to becoming a reality. In this paper we tackle this issue from two sides, first summarising what scientists have achieved so far, then discussing some of the ethical arguments in favour and against human cloning which are debated in the context of policy making and public consultation. Therapeutic cloning as a means to improve and save lives has uncontroversial moral value. As to human reproductive cloning, we consider and assess some common objections and failing to see them as conclusive. We do recognise, though, that there will be problems at the level of policy and regulation that might either impair the implementation of human reproductive cloning or make its accessibility restricted in a way that could become difficult to justify on moral grounds. We suggest using the time still available before human reproductive cloning is attempted successfully to create policies and institutions that can offer clear directives on its legitimate applications on the basis of solid arguments, coherent moral principles, and extensive public consultation.

  3. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

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    Xiaochun Duan

    2016-01-01

    Full Text Available Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH. Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

  4. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Science.gov (United States)

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  5. Studying human immunodeficiencies in humans: advances in fundamental concepts and therapeutic interventions [version 1; referees: 3 approved

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    Helen Su

    2017-03-01

    Full Text Available Immunodeficiencies reveal the crucial role of the immune system in defending the body against microbial pathogens. Given advances in genomics and other technologies, this is currently best studied in humans who have inherited monogenic diseases. Such investigations have provided insights into how gene products normally function in the natural environment and have opened the door to new, exciting treatments for these diseases.

  6. Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51.

    Science.gov (United States)

    Sharma, Aruna; Muresanu, Dafin F; Lafuente, José Vicente; Sjöquist, Per-Ove; Patnaik, Ranjana; Ryan Tian, Z; Ozkizilcik, Asya; Sharma, Hari S

    2018-01-01

    The possibility that traumatic brain injury (TBI) occurring in a cold environment exacerbates brain pathology and oxidative stress was examined in our rat model. TBI was inflicted by making a longitudinal incision into the right parietal cerebral cortex (2 mm deep and 4 mm long) in cold-acclimatized rats (5 °C for 3 h daily for 5 weeks) or animals at room temperature under Equithesin anesthesia. TBI in cold-exposed rats exhibited pronounced increase in brain lucigenin (LCG), luminol (LUM), and malondialdehyde (MDA) and marked pronounced decrease in glutathione (GTH) as compared to identical TBI at room temperature. The magnitude and intensity of BBB breakdown to radioiodine and Evans blue albumin, edema formation, and neuronal injuries were also exacerbated in cold-exposed rats after injury as compared to room temperature. Nanowired delivery of H-290/51 (50 mg/kg) 6 and 8 h after injury in cold-exposed group significantly thwarted brain pathology and oxidative stress whereas normal delivery of H-290/51 was neuroprotective after TBI at room temperature only. These observations are the first to demonstrate that (i) cold aggravates the pathophysiology of TBI possibly due to an enhanced production of oxidative stress, (ii) and in such conditions, nanodelivery of antioxidant compound has superior neuroprotective effects, not reported earlier.

  7. New Advances in Nanotechnology-Based Diagnosis and Therapeutics for Breast Cancer: An Assessment of Active-Targeting Inorganic Nanoplatforms.

    Science.gov (United States)

    Falagan-Lotsch, Priscila; Grzincic, Elissa M; Murphy, Catherine J

    2017-01-18

    Breast cancer is a major cause of suffering and mortality among women. Limitations in the current diagnostic methods and treatment approaches have led to new strategies to positively impact the survival rates and quality of life of breast cancer patients. Nanotechnology offers a real possibility of mitigating breast cancer mortality by early-stage cancer detection and more precise diagnosis as well as more effective treatments with minimal side effects. The current nanoplatforms approved for breast cancer therapeutics are based on passive tumor targeting using organic nanoparticles and have not provided the expected significant improvements in the clinic. In this review, we present the emerging approaches in breast cancer nanomedicine based on active targeting using versatile inorganic nanoplatforms with biomedical relevance, such as gold, silica, and iron oxide nanoparticles, as well as their efficacy in breast cancer imaging, drug and gene delivery, thermal therapy, combinational therapy, and theranostics in preclinical studies. The main challenges for clinical translation and perspectives are discussed.

  8. Antioxidants in Translational Medicine

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    Schmidt, Harald H.H.W.; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis

    2015-01-01

    Abstract Significance: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. Recent Advances: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Critical Issues: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Future Directions: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities. Antioxid. Redox Signal. 23, 1130–1143. PMID:26154592

  9. Sun-downing and integration for the advancement of science and therapeutics: the National Institute on Substance Use Disorders (NISUD).

    Science.gov (United States)

    Grabowski, John

    2010-12-01

    The National Institutes of Health (NIH) is the most prominent funding source for scientific research in the world. It is also a complex and diverse organization, having multiple institutes, centers and offices. NIH emphasizes the need for innovation and collaboration in research to discover critical knowledge, enhance health and prevent disease. Advancement in science requires not only sophisticated methods, but also logical organization. Here, an overview of ‘behavioral research’ (writ large) at NIH is presented, focusing upon the common trinity of ‘alcohol, tobacco/nicotine and other drugs’ and programmatic overlap across entities. Consideration is also given to the origins of institutes and their historical movement across organizational boundaries. Specific issues, concerns and advantages of integration of the National Institute on Drug Abuse and National Institute on Alcoholism and Alcohol Abuse are addressed. It is concluded that advances in understanding, treating and preventing substance use disorders would best be served by (1)review and integration of all related research throughout NIH, (2) logical placement of leadership for this activity in a single institute, here entitled the National Institute on Substance Use Disorders, and (3) close collaboration of this institute with its complementary partner, the National Institute on Mental Health. Thus, NIH can establish an organizational structure and collaborations reflecting the realities of the scientific and disease/health domains. This would make a prominent statement to the world scientific and health communities regarding NIH recognition of the need for innovation (scientific and organizational) and focus upon these myriad interrelated and costly problems.

  10. Radiofrequency Ablation in the Management of Advanced Stage Thymomas: A Case Report on a Novel Multidisciplinary Therapeutic Approach

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    Panagiotis Paliogiannis

    2014-01-01

    Full Text Available We describe in this report a case of successful radiofrequency ablation of an unresectable stage III-type B3 thymoma, and we discuss the role of this novel approach in the management of patients with advanced stage thymoma. The patient, a 59-year-old Caucasian male underwent neoadjuvant chemotherapy with only a slight reduction of the mass. Subsequently, an explorative sternotomy and debulking were performed; before closing the thorax, radiofrequency ablation of the residual tumor was carried out and a partial necrosis of the mass was achieved. A further percutaneous radiofrequency ablation was performed subsequently, obtaining complete necrosis of the lesion. Successively, the patient underwent adjuvant radiotherapy. As a result of this multidisciplinary treatment, complete and stable response was obtained. It is hard to say which of the single treatments had the major impact on cure; nevertheless, the results obtained suggest that radiofrequency ablation must be taken into account for the treatment of advanced stage thymomas, and its effectiveness must be further assessed in future studies.

  11. Study of the therapeutic effects of an advanced hippotherapy simulator in children with cerebral palsy: a randomised controlled trial

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    Oliván Barbara

    2010-04-01

    Full Text Available Abstract Background Although hippotherapy treatment has been demonstrated to have therapeutic effects on children with cerebral palsy, the samples used in research studies have been very small. In the case of hippotherapy simulators, there are no studies that either recommend or advise against their use in the treatment of children with cerebral palsy. The aim of this randomised clinical study is to analyse the therapeutic effects or the contraindications of the use of a commercial hippotherapy simulator on several important factors relating to children with cerebral palsy such as their motor development, balance control in the sitting posture, hip abduction range of motion and electromyographic activity of adductor musculature. Methods/Design The study is a randomised controlled trial. It will be carried out with a sample of 37 children with cerebral palsy divided into two treatment groups. Eligible participants will be randomly allocated to receive either (a Treatment Group with hippotherapy simulator, maintaining sitting posture, with legs in abduction and rhythmic movement of the simulator or (b Treatment Group maintaining sitting posture, with legs in abduction and without rhythmic movement of the simulator. Data collection and analysis: all measurements will be carried out by a specially trained blind assessor. To ensure standardization quality of the assessors, an inter-examiner agreement will be worked out at the start of the study. The trial is funded by the Department of Research, Innovation and Development of the Regional Government of Aragon (Official Bulletin of Aragon 23 July 2007, project number PM059/2007. Discussion Interest in this project is due to the following factors: Clinical originality (there are no previous studies analysing the effect of simulators on the population group of children with CP, nor any studies using as many variables as this project; Clinical impact (infantile cerebral palsy is a chronic multisystemic

  12. Study of the therapeutic effects of an advanced hippotherapy simulator in children with cerebral palsy: a randomised controlled trial.

    Science.gov (United States)

    Herrero, Pablo; Asensio, Angel; García, Elena; Marco, Alvaro; Oliván, Barbara; Ibarz, Alejandro; Gómez-Trullén, Eva M; Casas, Roberto

    2010-04-16

    Although hippotherapy treatment has been demonstrated to have therapeutic effects on children with cerebral palsy, the samples used in research studies have been very small. In the case of hippotherapy simulators, there are no studies that either recommend or advise against their use in the treatment of children with cerebral palsy. The aim of this randomised clinical study is to analyse the therapeutic effects or the contraindications of the use of a commercial hippotherapy simulator on several important factors relating to children with cerebral palsy such as their motor development, balance control in the sitting posture, hip abduction range of motion and electromyographic activity of adductor musculature. The study is a randomised controlled trial. It will be carried out with a sample of 37 children with cerebral palsy divided into two treatment groups. Eligible participants will be randomly allocated to receive either (a) Treatment Group with hippotherapy simulator, maintaining sitting posture, with legs in abduction and rhythmic movement of the simulator or (b) Treatment Group maintaining sitting posture, with legs in abduction and without rhythmic movement of the simulator. all measurements will be carried out by a specially trained blind assessor. To ensure standardization quality of the assessors, an inter-examiner agreement will be worked out at the start of the study. The trial is funded by the Department of Research, Innovation and Development of the Regional Government of Aragon (Official Bulletin of Aragon 23 July 2007), project number PM059/2007. Interest in this project is due to the following factors: Clinical originality (there are no previous studies analysing the effect of simulators on the population group of children with CP, nor any studies using as many variables as this project); Clinical impact (infantile cerebral palsy is a chronic multisystemic condition that affects not only the patient but also the patient's family and their close

  13. An Official American Thoracic Society Research Statement: Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling.

    Science.gov (United States)

    Prakash, Y S; Halayko, Andrew J; Gosens, Reinoud; Panettieri, Reynold A; Camoretti-Mercado, Blanca; Penn, Raymond B

    2017-01-15

    Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulatory issues that deter progress of AR research and development of therapeutics targeting AR and to propose approaches and solutions to these specific problems. This Statement is not intended to provide clinical practice recommendations on any disease in which AR is observed and/or plays a role. An international multidisciplinary group from within academia, industry, and the National Institutes of Health, with expertise in multimodal approaches to the study of airway structure and function, pulmonary research and clinical practice in obstructive lung disease, and drug discovery platforms was invited to participate in one internet-based and one face-to-face meeting to address the above-stated goals. Although the majority of the analysis related to AR was in asthma, AR in other diseases was also discussed and considered in the recommendations. A literature search of PubMed was performed to support conclusions. The search was not a systematic review of the evidence. Multiple conceptual, logistical, economic, and regulatory deterrents were identified that limit the performance of AR research and impede accelerated, intensive development of AR-focused therapeutics. Complementary solutions that leverage expertise of academia and industry were proposed to address them. To date, numerous factors related to the intrinsic difficulty in performing AR research, and economic forces that are disincentives for the pursuit of AR treatments, have thwarted the ability to understand AR pathology and mechanisms and to address it clinically. This ATS Research Statement identifies potential solutions for each of these factors and emphasizes the importance of educating the global research community as to the

  14. "Electro-clinical syndromes" with onset in paediatric age: the highlights of the clinical-EEG, genetic and therapeutic advances

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    Parisi Pasquale

    2011-12-01

    Full Text Available Abstract The genetic causes underlying epilepsy remain largely unknown, and the impact of available genetic data on the nosology of epilepsy is still limited. Thus, at present, classification of epileptic disorders should be mainly based on electroclinical features. Electro-clinical syndrome is a term used to identify a group of clinical entities showing a cluster of electro-clinical characteristics, with signs and symptoms that together define a distinctive, recognizable, clinical disorder. These often become the focus of treatment trials as well as of genetic, neuropsychological, and neuroimaging investigations. They are distinctive disorders identifiable on the basis of a typical age onset, specific EEG characteristics, seizure types, and often other features which, when taken together, permit a specific diagnosis which, in turn, often has implications for treatment, management, and prognosis. Each electro-clinical syndrome can be classified according to age at onset, cognitive and developmental antecedents and consequences, motor and sensory examinations, EEG features, provoking or triggering factors, and patterns of seizure occurrence with respect to sleep. Therefore, according to the age at onset, here we review the more frequently observed paediatric electro-clinical syndrome from their clinical-EEG, genetic and therapeutic point of views.

  15. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

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    Smita Raghuvanshi

    2014-01-01

    Full Text Available Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

  16. Recent advances in mass spectrometry-based approaches for proteomics and biologics: Great contribution for developing therapeutic antibodies.

    Science.gov (United States)

    Iwamoto, Noriko; Shimada, Takashi

    2017-12-22

    Since the turn of the century, mass spectrometry (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. The spectral data from MS contain various types of information. The benefits of improving the resolution of MS data include accurate molecular structural-derived information, and as a result, we can obtain a refined biomolecular structure determination in a sequential and large-scale manner. Moreover, in MS data, not only accurate structural information but also the generated ion amount plays an important rule. This progress has greatly contributed a research field that captures biological events as a system by comprehensively tracing the various changes in biomolecular dynamics. The sequential changes of proteome expression in biological pathways are very essential, and the amounts of the changes often directly become the targets of drug discovery or indicators of clinical efficacy. To take this proteomic approach, it is necessary to separate the individual MS spectra derived from each biomolecule in the complexed biological samples. MS itself is not so infinite to perform the all peak separation, and we should consider improving the methods for sample processing and purification to make them suitable for injection into MS. The above-described characteristics can only be achieved using MS with any analytical instrument. Moreover, MS is expected to be applied and expand into many fields, not only basic life sciences but also forensic medicine, plant sciences, materials, and natural products. In this review, we focus on the technical fundamentals and future aspects of the strategies for accurate structural identification, structure-indicated quantitation, and on the challenges for pharmacokinetics of high

  17. Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

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    Anton M Markovets

    Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

  18. Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer.

    Science.gov (United States)

    Brägelmann, Johannes; Klümper, Niklas; Offermann, Anne; von Mässenhausen, Anne; Böhm, Diana; Deng, Mario; Queisser, Angela; Sanders, Christine; Syring, Isabella; Merseburger, Axel S; Vogel, Wenzel; Sievers, Elisabeth; Vlasic, Ignacija; Carlsson, Jessica; Andrén, Ove; Brossart, Peter; Duensing, Stefan; Svensson, Maria A; Shaikhibrahim, Zaki; Kirfel, Jutta; Perner, Sven

    2017-04-01

    Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities ( n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer ( n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq. Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19 In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro , inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion. Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. Clin Cancer Res; 23(7); 1829-40. ©2016 AACR . ©2016 American Association for Cancer Research.

  19. Amino acid-based advanced liquid formulation development for highly concentrated therapeutic antibodies balances physical and chemical stability and low viscosity.

    Science.gov (United States)

    Kemter, Kristina; Altrichter, Jens; Derwand, Roland; Kriehuber, Thomas; Reinauer, Eva; Scholz, Martin

    2018-04-16

    To develop highly concentrated therapeutic antibodies enabling convenient subcutaneous application, well stabilizing pharmaceutical formulations with low viscosities are considered to be key. The purpose of this study was to select specific amino acid combinations that reduce and balance aggregation, fragmentation and chemical degradation and also lower viscosity of highly concentrated liquid antibodies. As a model, the therapeutically well-established antibody trastuzumab (25 - >200 mg/mL) in liquid formulation was used. Pre-testing of formulations based on a stabilizing and protecting solutions (SPS®) platform was conducted in a thermal unfolding model using Differential Scanning Fluorimetry (DSF) and accelerated aging at 37 °C and 45 °C. Pre-selected amino acid combinations were further iteratively adjusted to obtain stable highly concentrated antibody formulations with low viscosity. Size Exclusion Chromatography (SE-HPLC) revealed significantly lower aggregation and fragmentation at specific amino acid:sugar and protein:excipient ratios. Dynamic viscosities <20 mPa∗s of highly concentrated trastuzumab (≥200 mg/mL) were measured by falling ball viscosimetry. Moreover, less chemical degradation was found by Cationic Exchange Chromatography (CEX -HPLC) even after six months liquid storage at 25 °C. In conclusion, specifically tailored and advanced amino acid-based liquid formulations avoid aggregation and enable the development of stable and low viscous highly concentrated biopharmaceuticals. This article is protected by copyright. All rights reserved.

  20. Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

    Science.gov (United States)

    Milan, Aroha Sanchez; Campmany, Ana Cristina Calpena; Naveros, Beatriz Clares

    2017-01-01

    Melatonin is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective in a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on melatonin for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. This review focuses on nanocarrier production strategies, dermal melatonin application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted melatonin delivery have also been discussed. In the current review, we have revised relevant articles of the available literature using the major scientific databases. One hundred and thirteen papers were included in the review, the majority of which represent latest researches in nanosized platforms for the dermal delivery of melatonin including liposomes, ethosomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles and cyclodextrins. Furthermore, relevant papers reporting in vitro and in vivo application studies of these nano-based melatonin platforms were also discussed. The use of nanoplatforms for the dermal melatonin delivery as antioxidant agent could improve the efficacy of conventional melatonin administration due to the preservation of the drug from premature oxidation and the enhancement of drug permeation through the skin providing greater exposure times. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Treatment of stable COPD: antioxidants

    Directory of Open Access Journals (Sweden)

    W. MacNee

    2005-09-01

    Full Text Available There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with chronic obstructive pulmonary disease (COPD and this results in an imbalance between oxidants/antioxidants or oxidative stress, which may play a role in many of the processes involved in the pathogenesis of COPD. These include enhanced proteolytic activity, mucus hypersecretion and the enhanced inflammatory response in the lungs to inhaling tobacco smoke, which is characteristic of COPD. COPD is now recognised to have multiple systemic consequences, such as weight loss and skeletal muscle dysfunction. It is now thought that oxidative stress may extend beyond the lungs and is involved in these systemic effects. Antioxidant therapy therefore would seem to be a logical therapeutic approach in chronic obstructive pulmonary disease. There is a need for more potent antioxidant therapies to test the hypothesis that antioxidant drugs may be a new therapeutic strategy for the prevention and treatment of chronic obstructive pulmonary disease.

  2. Therapeutic effect of intra-arterial chemotherapy with DDP and 5-FU via bilateral uterine arteries for advanced uterine cervical cancer

    International Nuclear Information System (INIS)

    Zhou Kang; Li Xiaoguang; Jin Zhengyu; Yang Ning; Liu Wei; Pan Jie; Zhang Xiaobo; Shi Haifeng; Sun Hao; Wang Zhiwei

    2010-01-01

    Objective: To evaluate the therapeutic effect of intra-arterial chemotherapy with Ddp and 5-Fu via bilateral uterine arteries for advanced uterine cervical cancer. Methods: During the period of Jan. 2006-Jan. 2009, initial intra-arterial chemotherapy by using a combination of Ddp and 5-Fu via bilateral uterine arteries was performed in 72 patients (mean age 42.9 years) with advanced uterine cervical caner. Of 72 patients, stage I b2 cervical cancer was confirmed in 28, stage II a in 12 and stage II b in 32. Pathologically, cervical squamous cell carcinoma was seen in 56 and cervical adenocarcinoma in 16 patients. Ultrasonography and physical examination were conducted both before and after intra-arterial chemotherapy. The therapeutic results,complications,the surgical resection rate and the pathologic findings were observed and statistically analyzed. Results: Fifty-four patients received one treatment course and 18 patients received two treatment courses. The over all response rate was 77.8%. The response rates of patients with I b2, II a and II b cervical cancer were 92.9%, 83.3% and 62.5% respectively, the difference between three groups was statistically significant (P < 0.05). And the response rates of patients with squamous cell carcinoma and adenocarcinoma were 85.7% and 50.0% respectively, the difference between the two was statistically significant (P < 0.05). The most common side-effects included gastrointestinal symptoms and bone marrow suppression. Thirty-four patients received radical hysterectomy,among them, 22 (78.6%) had stage I b2, 8 (66.7%) had stage II a and 4 (12.5%) had stage II b cervical cancer (P < 0.05). Pathologic exam found no vaginal invasion and ovarian metastasis in all 34 patients. The occurrence of metastasis to lymph nodes and para uterine infiltration were 17.6% and 11.8% respectively. Conclusion: Intra-arterial chemotherapy with a combination of DDP and 5-Fu via bilateral uterine arteries can safely and effectively reduce the

  3. N-butanol extracts of Morinda citrifolia suppress advanced glycation end products (AGE)-induced inflammatory reactions in endothelial cells through its anti-oxidative properties.

    Science.gov (United States)

    Ishibashi, Yuji; Matsui, Takanori; Isami, Fumiyuki; Abe, Yumi; Sakaguchi, Tatsuya; Higashimoto, Yuichiro; Yamagishi, Sho-Ichi

    2017-03-04

    Advanced glycation end products (AGEs), senescent macroprotein derivatives formed during a normal aging process and acceleratedly under diabetic conditions, play a role in atherosclerotic cardiovascular disease. AGEs cause endothelial cell (EC) damage, an initial trigger for atherosclerosis through the interaction with a receptor for AGEs (RAGE). We have previously shown that n-butanol extracts of Morinda citrifolia (noni), a plant belonging to the family Rubiaceae, block the binding of AGEs to RAGE in vitro. In this study, we examined the effects of n-butanol extracts of noni on reactive oxygen species (ROS) generation and inflammatory reactions on AGE-exposed human umbilical vein ECs (HUVECs). HUVECs were treated with 100 μg/ml AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni for 4 h. Then ROS generation and inflammatory and gene expression in HUVECs were evaluated by dihydroethidium staining and real-time reverse transcription-polymerase chain reaction analyses, respectively. THP-1 cell adhesion to HUVECs was measured after 2-day incubation of AGE-BSA or BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni. N-butanol extracts of noni at 670 ng/ml significantly inhibited the AGE-induced ROS generation and RAGE, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 gene expressions in HUVECs. AGEs significantly increased monocytic THP-1 cell adhesion to HUVECs, which was also prevented by 670 ng/ml n-butanol extracts of noni. The present study demonstrated for the first time that N-butanol extracts of noni could suppress the AGE-induced inflammatory reactions in HUVECs through its anti-oxidative properties via blocking of the interaction of AGEs with RAGE. Inhibition of the AGE-RAGE axis by n-butanol extracts of noni may be a novel nutraceutical strategy for the treatment of cardiovascular disease.

  4. Therapeutic advancements in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Alessandro eGozzetti

    2014-09-01

    Full Text Available Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

  5. Food Processing Antioxidants.

    Science.gov (United States)

    Hidalgo, F J; Zamora, R

    Food processing has been carried out since ancient times as a way to preserve and improve food nutritional and organoleptic properties. Although it has some undesirable consequences, such as the losses of some nutrients and the potential formation of toxic compounds, a wide range of benefits can be enumerated. Among them, the increased total antioxidant capacity of many processed foods has been known for long. This consequence has been related to both the release or increased availability of natural antioxidants and the de novo formation of substances with antioxidant properties as a consequence of the produced reactions. This review analyzes the chemical changes produced in foods during processing with special emphasis on the formation of antioxidants as a consequence of carbonyl-amine reactions produced by both carbohydrate- and lipid-derived reactive carbonyls. It discusses the lastest advances produced in the characterization of carbonyl-amine adducts and their potential action as primary (free radical scavengers), secondary (chelating and other ways to prevent lipid oxidation), and tertiary (carbonyl scavengers as a way to avoid lipid oxidation consequences) antioxidants. Moreover, the possibility of combining amino compounds with different hydrophobicity, such as aminophospholipids and proteins, with a wide array of reactive carbonyls points out to the use of carbonyl-amine reactions as a new way to induce the formation of a great variety of substances with antioxidant properties and very variable hydrophilia/lipophilia. All presented results point out to carbonyl-amine reactions as an effective method to generate efficacious antioxidants that can be used in food technology. © 2017 Elsevier Inc. All rights reserved.

  6. Phytochemical constituents and antioxidant activities of aqueous ...

    African Journals Online (AJOL)

    USER

    2010-08-02

    Aug 2, 2010 ... 0.05) than methanol extract (77.00 ± 0.84%). Nevertheless, methanol and aqueous extracts of C. afer possess anti-oxidative properties as well as bioactive metabolites. Thus, stem extracts of C. afer could serve as sources of antioxidants and bioactive compounds for nutrition and therapeutic purposes.

  7. COPD: balancing oxidants and antioxidants

    Directory of Open Access Journals (Sweden)

    Fischer BM

    2015-02-01

    Full Text Available Bernard M Fischer,1,* Judith A Voynow,2,* Andrew J Ghio3,* 1Department of Pediatrics, Duke University Medical Center, Durham, NC, USA; 2Department of Pediatrics, Children's Hospital of Richmond at Virginia Commonwealth University, Richmond, VA, USA; 3National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, USA *These authors contributed equally to this work Abstract: Chronic obstructive pulmonary disease (COPD is one of the most common chronic illnesses in the world. The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking. Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease. The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses. In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD. The complexity of COPD will necessitate a multi-target therapeutic approach. It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies. Keywords: cigarette smoking, mucins, gene regulation, Chinese herbs, acupuncture, dietary antioxidants

  8. Natural antioxidant vitamins: A review of their beneficial roles in ...

    African Journals Online (AJOL)

    This review supports the use of antioxidant vitamins as therapeutic agents in the management of diabetes mellitus and its complications, and also provides an insight into the potential pharmacological effects of natural antioxidant vitamins in diabetic conditions. These antioxidant vitamins can be used as safe supplements to ...

  9. Recent advances in biologically active compounds in herbs and spices: a review of the most effective antioxidant and anti-inflammatory active principles.

    Science.gov (United States)

    Rubió, Laura; Motilva, Maria-José; Romero, Maria-Paz

    2013-01-01

    Spices, like vegetables, fruit, and medicinal herbs, are known to possess a variety of antioxidant effects and other biological activities. Phenolic compounds in these plant materials are closely associated with their antioxidant activity, which is mainly due to their redox properties and their capacity to block the production of reactive oxygen species. More recently, their ability to interfere with signal transduction pathways involving various transcription factors, protein kinases, phosphatases, and other metabolic enzymes has also been demonstrated. Many of the spice-derived compounds which are potent antioxidants are of great interest to biologists and clinicians because they may help protect the human body against oxidative stress and inflammatory processes. It is important to study the bioactive compounds that can modulate target functions related to defence against oxidative stress, and that might be used to achieve health benefits individually. In the present review, an attempt has been made to summarize the most current scientific evidence about the in vitro and in vivo effects of the bioactive compounds derived from herbs and spices, focused on anti-inflammatory and antioxidant effects, in order to provide science-based evidence for the traditional uses and develop either functional foods or nutraceuticals.

  10. Potential of Lichen Compounds as Antidiabetic Agents with Antioxidative Properties: A Review

    Science.gov (United States)

    Karunaratne, Veranja

    2017-01-01

    The advancement in the knowledge of potent antioxidants has uncovered the way for greater insight in the treatment of diabetic complications. Lichens are a rich resource of novel bioactive compounds and their antioxidant potential is well documented. Herein we review the antidiabetic potential of lichens which have received considerable attention, in the recent past. We have correlated the antidiabetic and the antioxidant potential of lichen compounds. The study shows a good accordance between antioxidant and antidiabetic activity of lichens and points out the need to look into gathering the scarce and scattered data on biological activities for effective utilization. The review establishes that the lichen extracts, especially of Parmotrema sp. and Ramalina sp. have shown promising potential in both antidiabetic and antioxidant assays. Ubiquitous compounds, namely, zeorin, methylorsellinate, methyl-β-orcinol carboxylate, methyl haematommate, lecanoric acid, salazinic acid, sekikaic acid, usnic acid, gyrophoric acid, and lobaric acid have shown promising potential in both antidiabetic as well as antioxidant assays highlighting their potential for effective treatment of diabetic mellitus and its associated complications. The available compilation of this data provides the future perspectives and highlight the need for further studies of this potent herbal source to harvest more beneficial therapeutic antidiabetic drugs. PMID:28491237

  11. Characterization of patients with diabetic foot disease presenting to an Irish Podiatry Centre: profiling suitability for entry to a clinical trial of advanced wound therapeutics.

    Science.gov (United States)

    Mahon, A M; MacGilchrist, C; McIntosh, C; O'Brien, T

    2017-08-01

    Diabetes mellitus, coined the 'Black Death of the Twenty-First Century', is associated with complications, including foot ulceration with potential loss of limb. There is a need for development of new wound therapies through completion of robust clinical trials. To profile demographics and wound characteristics of an Irish cohort with diabetes, forecast eligibility for entry to a clinical trial of advanced wound therapeutics, and adjust criteria to optimize eligibility for enrolment. A cross-sectional study of out-patients attending a Podiatry centre over 12 weeks was conducted. Information was collected through clinical assessment, including Neuropathy Disability Score and Ankle-Brachial Pressure Index. Ulcers were characterised as 'healing' or 'non-healing'; a 'healing' wound decreased by 30 % over the previous month, accomplished by retrospective analysis of files. Statistics, including binomial logistic regression and column analysis for eligibility assessment, were conducted. Seventy-four participants were identified with a mean age of 67 (± 8.79) years. Non-healing DFU status correlated significantly with larger wound area (P = 0.013), infection (P = 0.009), and greater degrees of ischaemia (P = 0.015). The eligibility criteria were modelled after those proposed by the EU consortium project REDDSTAR. In this Irish population, these criteria limit eligibility to 1.4 %. This research found an eligibility criterion of wound area 2-10 cm 2 for enrolment in a clinical trial of mesenchymal stromal cell therapy too restrictive. Extension of wound area to 1-10 cm 2 and the inclusion of neuro-ischaemic ulcers increased eligibility for enrolment from 1.4 to 20 %.

  12. Therapeutic Versatility of Resveratrol Derivatives

    OpenAIRE

    Waqas Nawaz; Zhongqin Zhou; Sa Deng; Xiaodong Ma; Xiaochi Ma; Chuangang Li; Xiaohong Shu

    2017-01-01

    Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol to enhance the bioavailability and the pharmacological activity of resveratrol. During the past decades, a large number of natural a...

  13. Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Michihiro Fujiwara

    2010-07-01

    Full Text Available Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC, and the non-psychoactive components cannabidiol (CBD, cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

  14. Antioxidative defense

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar, to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.

  15. Cells as advanced therapeutics: State-of-the-art, challenges, and opportunities in large scale biomanufacturing of high-quality cells for adoptive immunotherapies.

    Science.gov (United States)

    Dwarshuis, Nate J; Parratt, Kirsten; Santiago-Miranda, Adriana; Roy, Krishnendu

    2017-05-15

    Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Antimicrobial, Cytotoxic, Phytotoxic and Antioxidant Potential of Heliotropium strigosum Willd.

    Science.gov (United States)

    Khurm, Muhammad; Chaudhry, Bashir A; Uzair, Muhammad; Janbaz, Khalid H

    2016-07-28

    Background: Heliotropium strigosum Willd. (Chitiphal) is a medicinally important herb that belongs to the Boraginaceae family. Traditionally, this plant was used in the medication therapy of various ailments in different populations of the world. The aim of the study is to probe the therapeutic aspects of H. strigosum described in the traditional folklore history of medicines. Methods: In the present study, the dichloromethane crude extract of this plant was screened to explore the antimicrobial, cytotoxic, phytotoxic and antioxidant potential of H. strigosum . For antibacterial, antifungal and antioxidant activities, microplate alamar blue assay (MABA), agar tube dilution method and diphenyl picryl hydrazine (DPPH) radical-scavenging assay were used, respectively. The cytotoxic and phytotoxic potential were demonstrated by using brine shrimp lethality bioassay and Lemna minor assay. Results: The crude extract displayed positive cytotoxic activity in the brine shrimp lethality assay, with 23 of 30 shrimps dying at the concentration of 1000 µg/mL. It also showed moderate phytotoxic potential with percent inhibition of 50% at the concentration of 1000 µg/mL. The crude extract exhibited no significant antibacterial activity against Staphylococcus aureus , Shigella flexneri , Escherichia coli and Pseudomonas aeruginosa . Non-significant antifungal and radical scavenging activity was also shown by the dichloromethane crude extract. Conclusion: It is recommended that scientists focus on the identification and isolation of beneficial bioactive constituents with the help of advanced scientific methodologies that seems to be helpful in the synthesis of new therapeutic agents of desired interest.

  17. Meta-analysis: antioxidant supplements for liver diseases - the Cochrane Hepato-Biliary Group

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, L L; Nikolova, D

    2010-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  18. Antioxidants: Protecting Healthy Cells

    Science.gov (United States)

    ... and Nutrients Antioxidants - Protecting Healthy Cells Print Email Antioxidants - Protecting Healthy Cells Reviewed by Taylor Wolfram, MS, ... to cardiovascular disease and certain types of cancers. Antioxidants — such as vitamins C and E and carotenoids, ...

  19. Antioxidants and antioxidant capacity of human milk

    OpenAIRE

    Živković, Jelena; Sunarić, Slavica; Trutić, Nataša; Denić, Marko; Kocić, Gordana; Jovanović, Tatjana

    2015-01-01

    Milk contains plenty of enzymatic and non-enzymatic antioxidant components that probably account for the vital antioxidant protection of the infants at early stages of life against the development of complications induced by oxygen free radicals. Indigenous milk enzymes play a key role in regulating lactogenesis, including active involution of mammary gland. Moreover, they are essential constituents of antioxidation and the innate immune system of milk. Among antioxidant enzymes, superoxide d...

  20. Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

    Science.gov (United States)

    Zhang, Yaxiong; Zhang, Zhonghan; Huang, Xiaodan; Kang, Shiyang; Chen, Gang; Wu, Manli; Miao, Siyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2017-09-01

    Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib). Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Alternative end points to evaluate a therapeutic strategy in advanced colorectal cancer: evaluation of progression-free survival, duration of disease control, and time to failure of strategy--an Aide et Recherche en Cancerologie Digestive Group Study.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Shi, Qian; Buyse, Marc; Tournigand, Christophe; Sargent, Daniel J; Allegra, Carmen J; Goldberg, Richard M; de Gramont, Aimery

    2011-11-01

    Progression-free survival (PFS) is not an optimal end point to evaluate therapeutic strategies in advanced colorectal cancer (ACRC). Therefore, composite end points have been proposed to evaluate a chemotherapy strategy when sequential treatments are available: duration of disease control (DDC) and time to failure of strategy (TFS). The goal of this study was to evaluate these alternative end points and their potential surrogacy for overall survival (OS). We pooled individual patient data from three randomized trials evaluating chemotherapy strategy, which accrued 1,042 patients with previously untreated ACRC. In these trials, first-line treatment was either oxaliplatin- or irinotecan-based chemotherapy. Compared with TFS, DDC included neither time interval between progression and next sequence of treatment nor time to progression if the best result of the next sequence of treatment was progression. There was good correlation between DDC and OS (correlation of median: r, 0.62; correlation of hazard ratio [HR]: adjusted copula R(2), 0.72) and between TFS and OS (correlation of median: r, 0.59; correlation of HR: adjusted copula R(2), 0.67). There was no correlation between PFS and OS (correlation of median: r, 0.45; correlation of HR: adjusted copula R(2), 0.47). DDC and TFS roughly achieved the same results. Both are acceptable new end points to evaluate a therapeutic strategy in ACRC. Although TFS achieved a pragmatic evaluation of a multiline strategy, DDC captured the effect of a specific sequence in a therapeutic strategy.

  2. In vitro assessment of antioxidant, phytochemical and nutritional ...

    African Journals Online (AJOL)

    The antioxidant, phytochemical and nutritional properties of acetone, methanol and aqueous extracts of the leaves of Ocimum gratissimum (Linn) were investigated to evaluate the therapeutic and nutritional potential of the leaves of this plant. The antioxidant of the plant extracts were assessed against 1 ...

  3. Liposome Formulation of Fullerene-Based Molecular Diagnostic and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Zhiguo Zhou

    2013-10-01

    Full Text Available Fullerene medicine is a new but rapidly growing research subject. Fullerene has a number of desired structural, physical and chemical properties to be adapted for biological use including antioxidants, anti-aging, anti-inflammation, photodynamic therapy, drug delivery, and magnetic resonance imaging contrast agents. Chemical functionalization of fullerenes has led to several interesting compounds with very promising preclinical efficacy, pharmacokinetic and safety data. However, there is no clinical evaluation or human use except in fullerene-based cosmetic products for human skincare. This article summarizes recent advances in liposome formulation of fullerenes for the use in therapeutics and molecular imaging.

  4. Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: Analysis from the retroEMBRACE study

    DEFF Research Database (Denmark)

    LU, Fokdal; Sturdza, Alina; Mazeron, Renaud

    2016-01-01

    Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC/IS) applicat......Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC....../IS) applicators. The aim of this analysis was to evaluate the impact on local control and late morbidity of application of combined IS/IC brachytherapy in a large multicentre population. Material/methods 610 patients with LACC from the retroEMBRACE study were included. Patients were divided into an IC group (N...

  5. Protection against ionizing radiation by antioxidant nutrients and phytochemicals

    International Nuclear Information System (INIS)

    Weiss, Joseph F.; Landauer, Michael R.

    2003-01-01

    The potential of antioxidants to reduce the cellular damage induced by ionizing radiation has been studied in animal models for more than 50 years. The application of antioxidant radioprotectors to various human exposure situations has not been extensive although it is generally accepted that endogenous antioxidants, such as cellular non-protein thiols and antioxidant enzymes, provide some degree of protection. This review focuses on the radioprotective efficacy of naturally occurring antioxidants, specifically antioxidant nutrients and phytochemicals, and how they might influence various endpoints of radiation damage. Results from animal experiments indicate that antioxidant nutrients, such as vitamin E and selenium compounds, are protective against lethality and other radiation effects but to a lesser degree than most synthetic protectors. Some antioxidant nutrients and phytochemicals have the advantage of low toxicity although they are generally protective when administered at pharmacological doses. Naturally occurring antioxidants also may provide an extended window of protection against low-dose, low-dose-rate irradiation, including therapeutic potential when administered after irradiation. A number of phytochemicals, including caffeine, genistein, and melatonin, have multiple physiological effects, as well as antioxidant activity, which result in radioprotection in vivo. Many antioxidant nutrients and phytochemicals have antimutagenic properties, and their modulation of long-term radiation effects, such as cancer, needs further examination. In addition, further studies are required to determine the potential value of specific antioxidant nutrients and phytochemicals during radiotherapy for cancer

  6. Protection against ionizing radiation by antioxidant nutrients and phytochemicals

    International Nuclear Information System (INIS)

    Weiss, J.F.; Landauer, M.R.

    2003-01-01

    Full text: The potential of antioxidants to reduce the cellular damage induced by ionizing radiation has been studied in animal models for more than 50 years. The application of antioxidant radioprotectors to various human exposure situations has not been extensive although it is generally accepted that endogenous antioxidants, such as cellular non-protein thiols and antioxidant enzymes, provide some degree of protection. This review focuses on the radioprotective efficacy of naturally-occurring antioxidants, specifically antioxidant nutrients and phytochemicals, and how they might influence various endpoints of radiation damage. Results from animal experiments indicate that antioxidant nutrients, such as vitamin E and selenium compounds, are protective against lethality and other radiation effects but to a lesser degree than most synthetic protectors. Some antioxidant nutrients and phytochemicals have the advantage of low toxicity although they are generally protective when administered at pharmacological doses. Naturally-occurring antioxidants also may provide an extended window of protection against low-dose, low-dose-rate irradiation, including therapeutic potential when administered after irradiation. A number of phytochemicals, including caffeine, genistein, and melatonin, have multiple physiological effects, as well as antioxidant activity, which result in radioprotection in vivo. Many antioxidant nutrients and phytochemicals have antimutagenic properties, and their modulation of long-term radiation effects, such as cancer, needs further examination. In addition, further studies are required to determine the potential value of specific antioxidant nutrients and phytochemicals during radiotherapy for cancer

  7. Therapeutic radionuclides

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Hong, Young Don; Lee, So Young

    2006-01-01

    Since the development of sophisticated molecular carriers such as octereotides for peptide receptor targeting and monoclonal antibodies against various associated with specific tumor types, radionuclide therapy (RNT) employing open sources of therapeutic agents is promising modality for treatment of tumors. Furthermore, the emerging of new therapeutic regimes and new approaches for tumor treatment using radionuclide are anticipated in near future. In targeted radiotherapy using peptides and other receptor based carrier molecules, the use of radionuclide with high specific activity in formulating the radiopharmaceutical is essential in order to deliver sufficient number of radionuclides to the target site without saturating the target. In order to develop effective radiopharmaceuticals for therapeutic applications, it is crucial to carefully consider the choice of appropriate radionuclides as well as the carrier moiety with suitable pharmacokinetic properties that could result in good in vivo localization and desired excretion. Up to date, only a limited number of radionuclides have been applied in radiopharmaceutical development due to the constraints in compliance with their physical half-life, decay characteristics, cost and availability in therapeutic applications. In this review article, we intend to provide with the improved understanding of the factors of importance of appropriate radionuclide for therapy with respect to their physical properties and therapeutic applications

  8. Case studies on selected natural food antioxidants

    OpenAIRE

    Herrero, Miguel; Mendiola, J. A.; Cifuentes, Alejandro; Ibáñez, Elena

    2013-01-01

    In this chapter, a broad description of several case studies related to common antioxidants found in food-related products is presented. In this regard, special attention is put on the novel advanced environmentally-friendly extraction methods nowadays employed to extract and purify those potent antioxidants from natural matrices. A brief description of these extraction processes is provided together with some of the instrumentation needed. Besides, the studies carried out so f...

  9. Antiglycation and antioxidation properties of berberis lyceum and terminalia chebula: possible role in curing diabetes and slowing aging

    International Nuclear Information System (INIS)

    Khan, I.; Ahmad, H.; Ahmad, B.; Azam, S.

    2014-01-01

    Plants have been shown to possess a great potential to benefit mankind. Extracts from plants that have antiglycation and antioxidation abilities can be of great therapeutic value in reducing complication of diabetes and slowing down aging. Advanced glycation end-products (AGE's) formation due to non-enzymatic glycation and oxidative stress has been demonstrated in the pathogenesis of diabetic complications and aging processes. In this study we investigated the antiglycation and antioxidation potential of methanolic extracts of Berberis lyceum and Terminalia chebula. Results indicated that the methanolic extract of B. lyceum had more antiglycation ability with a Minimum inhibitory concentration (MIC50) of 123 meu g/mL as compared to the MIC50 of 110 meu g/ml of T. chebula. While the results of antioxidation assay showed that T. chebula has more antioxidation potential than B. lyceum. T. chebula had 46.55, 35.01 and 32.81% antioxidation potential at 0.5 mg, 0.25 mg and 0.125 mg respectively as compared to the 16.53, 16.09 and 15.10 % oxidation inhibition at same mass values by B. lycium. (author)

  10. Anti-glycation and anti-oxidation properties of Capsicum frutescens and Curcuma longa fruits: possible role in prevention of diabetic complication.

    Science.gov (United States)

    Khan, Ibrar; Ahmad, Haroon; Ahmad, Bashir

    2014-09-01

    The accumulation of advanced glycationend products (AGE's) in the body, due to the non-enzymatic glycation of proteins is associated with several pathological conditions like aging and diabetes mellitus. Hence a plant having anti-glycation and anti-oxidation potentials may serve as therapeutic agent for diabetic complications and aging. In this study the anti-glycation and anti-oxidation properties of crude methanolic extracts of fruits of Capsicum frutescens and Curcuma longa were investigated. Among the two C. frutescens had more anti-glycation ability with a minimum inhibitory concentration (MIC50) of 90βg/mLas compared to 324βg/mL MIC50 of C. longa. Curcuma longa had the more anti-oxidation potential i.e. 35.01, 30.83 and 28.08% at 0.5mg, 0.25mg and 0.125mg respectively.

  11. Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma.

    Science.gov (United States)

    Marconato, L; Stefanello, D; Sabattini, S; Comazzi, S; Riondato, F; Laganga, P; Frayssinet, P; Pizzoni, S; Rouquet, N; Aresu, L

    2015-09-22

    The aim of this non-randomized controlled trial was to compare time to progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy alone in dogs with newly diagnosed, clinically advanced, histologically confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from dogs' resected lymph nodes and administered as an intradermal injection. Forty-five client-owned dogs were enrolled: 20 dogs were treated with dose-intense chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine. TTP was significantly longer for dogs treated with chemo-immunotherapy versus those receiving chemotherapy only (median, 209 versus 85 days, respectively, P=0.015). LSS was not significantly different between groups: dogs treated with chemo-immunotherapy had a median survival of 349 days, and those treated with chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated dogs, those mounting an immune response had a significantly longer TTP and LSS than those with no detectable response (P=0.012 and P=0.003, respectively). Collectively these results demonstrate that vaccination with HSPPCs-HA may produce clinical benefits with no increased toxicity, thereby providing a strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Antioxidants can increase melanoma metastasis in mice.

    Science.gov (United States)

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-07

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. Copyright © 2015, American Association for the Advancement of Science.

  13. Therapeutic Response in Patients with Advanced Malignancies Treated with Combined Dendritic Cell–Activated T Cell Based Immunotherapy and Intensity–Modulated Radiotherapy

    International Nuclear Information System (INIS)

    Hasumi, Kenichiro; Aoki, Yukimasa; Watanabe, Ryuko; Hankey, Kim G.; Mann, Dean L.

    2011-01-01

    Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation-related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies

  14. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  15. Therapeutic Gardening

    OpenAIRE

    Turner, Phyllis; Fox, Laurie; Parkhurst, James A. (James Albert)

    2013-01-01

    Gardening can be therapeutic for anyone and has been used as therapy for those with physical, emotional and social disabilities, for children, and for those who are elderly. Through careful adaptations to the garden, the gardener and the plants, almost anyone can benefit from the activity of gardening

  16. Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Gu, Yuanlong; Lv, Huimin; Zhao, Juan; Li, Qi; Mu, Guannan; Li, Jiade; Wuyang, Jiazi; Lou, Ge; Wang, Ruitao; Zhang, Yanqiao; Huang, Xiaoyi

    2017-09-01

    Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACTcells in patients who received ≥4cycles of ACT was higher than that in patients treated with cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC. Copyright © 2017. Published by Elsevier B.V.

  17. Post-discharge survival outcomes of patients with advanced cancer from UT MD Anderson Cancer Center Investigational Cancer Therapeutics (phase I trials) Inpatient unit

    Science.gov (United States)

    Kinahan, Holly; Maiti, Abhishek; Hess, Kenneth; Dempsey, Jennifer; Beatty, Laura; Baldwin, Sarah; Hong, David S.; Naing, Aung; Fu, Siqing; Tsimberidou, Apostolia M.; Piha-Paul, Sarina; Janku, Filip; Karp, Daniel; Reddy, Suresh; Yennu, Sriram; Epner, Daniel; Bruera, Eduardo; Meric-Bernstam, Funda; Falchook, Gerald; Subbiah, Vivek

    2016-01-01

    Background Patients with advanced cancer who progress on standard therapy are potential candidates for phase I clinical trials. Due to their aggressive disease and complex co-morbid conditions, these patients often need inpatient admission. This study assessed the outcomes of such patients after they were discharged to hospice care. Patients and methods We performed a retrospective analysis of patients with solid tumor malignancies who were discharged to hospice care from the inpatient service. Results One hundred thirty-three patients were included in the study cohort. All patients had metastatic disease and an ECOG PS ≥3. The median survival after discharge to hospice from an inpatient setting was 16 days, with a survival rate of 5% at 3 months after discharge. The median survival after the last cancer treatment was 46 days, with survival of 17% at 3 months, and 5% at 6 months. Patients with LDH >618 IU/L had a median post-discharge survival of 11 days versus 20 days for patients with LDH ≤618 IU/L. Conclusions Patients with metastatic cancer participating in phase I trials who have poor performance status and require inpatient admission have a very short survival after discharge to hospice. A high LDH level predicts an even shorter survival. PMID:27802448

  18. Antioxidant-Induced Stress

    Directory of Open Access Journals (Sweden)

    Robert D. Kross

    2012-02-01

    Full Text Available Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals.

  19. Interactions of silica nanoparticles with therapeutics for oxidative stress attenuation in neurons

    Science.gov (United States)

    White-Schenk, Desiree; Shi, Riyi; Leary, James F.

    2015-03-01

    Oxidative stress plays a major role in many disease pathologies, notably in the central nervous system (CNS). For instance, after initial spinal cord injury, the injury site tends to increase during a secondary chemical injury process based on oxidative stress from necrotic cells and the inflammatory response. Prevention of this secondary chemical injury would represent a major advance in the treatment of people with spinal cord injuries. Few therapeutics are useful in combating such stress in the CNS due to side effects, low efficacy, or half-life. Mesoporous silica nanoparticles show promise for delivering therapeutics based on the formation of a porous network during synthesis. Ideally, they increase the circulation time of loaded therapeutics to increase the half-life while reducing overall concentrations to avoid side effects. The current study explored the use of silica nanoparticles for therapeutic delivery of anti-oxidants, in particular, the neutralization of acrolein which can lead to extensive tissue damage due to its ability to generate more and more copies of itself when it interacts with normal tissue. Both an FDA-approved therapeutic, hydralazine, and natural product, epigallocatechin gallate, were explored as antioxidants for acrolein with nanoparticles for increased efficacy and stability in neuronal cell cultures. Not only were the nanoparticles explored in neuronal cells, but also in a co-cultured in vitro model with microglial cells to study potential immune responses to near-infrared (NIRF)-labeled nanoparticles and uptake. Studies included nanoparticle toxicity, uptake, and therapeutic response using fluorescence-based techniques with both dormant and activated immune microglia co-cultured with neuronal cells.

  20. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

    International Nuclear Information System (INIS)

    Helisch, Andreas; Foerster, Gregor J.; Reber, Helmut; Buchholz, Hans-Georg; Bartenstein, Peter; Arnold, Rudolf; Goeke, Burkhard; Weber, Matthias M.; Wiedenmann, Bertram; Pauwels, Stanislas; Haus, Ulrike; Bouterfa, Hakim

    2004-01-01

    For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90 Y is frequently used [ 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86 Y-DOTA-Phe 1 -Tyr 3 -octreotide (considered as the gold standard) and the commercially available 111 In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 ( 86 Y-DOTA-Phe 1 -Tyr 3 -octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 ( 111 In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86 Y-DOTA-Phe 1 -Tyr 3 -octreotide, dosimetry with 111 In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy. (orig.)

  1. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours.

    Science.gov (United States)

    Helisch, Andreas; Förster, Gregor J; Reber, Helmut; Buchholz, Hans-Georg; Arnold, Rudolf; Göke, Burkhard; Weber, Matthias M; Wiedenmann, Bertram; Pauwels, Stanislas; Haus, Ulrike; Bouterfa, Hakim; Bartenstein, Peter

    2004-10-01

    For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.

  2. Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.

    Science.gov (United States)

    Xia, Peng; Deng, Qing; Gao, Jin; Yu, Xiaolan; Zhang, Yang; Li, Jingjing; Guan, Wen; Hu, Jianjun; Tan, Quanhui; Zhou, Liang; Han, Wei; Yuan, Yunsheng; Yu, Yan

    2016-05-15

    Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cells in vitro. Anti-RAGE was found to inhibit hepatic stellate cell proliferation in vivo and in vitro. Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Nanomedicine in the ROS-mediated pathophysiology: Applications and clinical advances.

    Science.gov (United States)

    Nash, Kevin M; Ahmed, Salahuddin

    2015-11-01

    Reactive oxygen species (ROS) are important in regulating normal cell physiological functions, but when produced in excess lead to the augmented pathogenesis of various diseases. Among these, ischemia reperfusion injury, Alzheimer's disease and rheumatoid arthritis are particularly important. Since ROS can be counteracted by a variety of antioxidants, natural and synthetic antioxidants have been developed. However, due to the ubiquitous production of ROS in living systems, poor in vivo efficiency of these agents and lack of target specificity, the current clinical modalities to treat oxidative stress damage are limited. Advances in the developing field of nanomedicine have yielded nanoparticles that can prolong antioxidant activity, and target specificity of these agents. This article reviews recent advances in antioxidant nanoparticles and their applications to manage oxidative stress-mediated diseases. Production of reactive oxygen species (ROS) is a purely physiological process in many disease conditions. However, excessive and uncontrolled production will lead to oxidative stress and further tissue damage. Advances in nanomedicine have provided many novel strategies to try to combat and counteract ROS. In this review article, the authors comprehensively highlighted the current status and future developments in using nanotechnology for providing novel therapeutic options in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Profiling Prostate Cancer Therapeutic Resistance

    OpenAIRE

    Cameron A. Wade; Natasha Kyprianou

    2018-01-01

    The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival ...

  5. Nano-antioxidants: An emerging strategy for intervention against neurodegenerative conditions.

    Science.gov (United States)

    Sandhir, Rajat; Yadav, Aarti; Sunkaria, Aditya; Singhal, Nitin

    2015-10-01

    Oxidative stress has for long been linked to the neuronal cell death in many neurodegenerative conditions. Conventional antioxidant therapies have been less effective in preventing neuronal damage caused by oxidative stress due to their inability to cross the blood brain barrier. Nanoparticle antioxidants constitute a new wave of antioxidant therapies for prevention and treatment of diseases involving oxidative stress. It is believed that nanoparticle antioxidants have strong and persistent interactions with biomolecules and would be more effective against free radical induced damage. Nanoantioxidants include inorganic nanoparticles possessing intrinsic antioxidant properties, nanoparticles functionalized with antioxidants or antioxidant enzymes to function as an antioxidant delivery system. Nanoparticles containing antioxidants have shown promise as high-performance therapeutic nanomedicine in attenuating oxidative stress with potential applications in treating and preventing neurodegenerative conditions. However, to realize the full potential of nanoantioxidants, negative aspects associated with the use of nanoparticles need to be overcome to validate their long term applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Cysteine-containing peptides having antioxidant properties

    Science.gov (United States)

    Bielicki, John K [Castro Valley, CA

    2008-10-21

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  7. Frontiers in nano-therapeutics

    CERN Document Server

    Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

    2017-01-01

    This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

  8. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  9. Antioxidants in liver health

    Science.gov (United States)

    Casas-Grajales, Sael; Muriel, Pablo

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

  10. Antiglycation and antioxidation properties of Juglans regia and Calendula officinalis: possible role in reducing diabetic complications and slowing down ageing.

    Science.gov (United States)

    Ahmad, Haroon; Khan, Ibrar; Wahid, Abdul

    2012-09-01

    Accumulation of advanced glycation end products (AGEs) in the body due to the non-enzymatic glycation of proteins and oxidation is associated with aging and diabetes mellitus. In this study we wanted to investigate the antiglycation and antioxidation potential of two medicinal plants: Juglans regia and Calendula officinalis. In-vitro investigation was carried out to discover the antiglycation and antioxidation potential of J. regia and C. officinalis. Using an Ultraviolet Double-beam Spectrophotometer, we evaluated the antiglycation property of the crude methanolic extracts of J. regia and C. officinalis by assessing their ability to inhibit the Maillard reaction. Employing the same instrument we also measured the antioxidation potential of these plant extracts using the nitric oxide (NO) free radical-scavenging assay. J. regia had greater antiglycation ability, with a minimum inhibitory concentration (MIC50) of 28 microg/mL as compared with that of C. officinalis (270 microg/mL). C. officinalis had greater antioxidation potential (26.10, 22.07 and 16.06% at 0.5 mg, 0.25 mg and 0.125 mg, respectively, as compared with 18.15, 16.50 and 16.06% of J. regia, respectively). J. regia and C. officinalis inhibited the Maillard reaction and prevented oxidation in-vitro. Hence, the extracts of these plants could have therapeutic uses in curbing chronic diabetic complications and slowing down aging.

  11. Innovative Therapeutics

    Directory of Open Access Journals (Sweden)

    Laura M.G. Meems, MD, PhD

    2016-12-01

    Full Text Available Natriuretic peptides (NPs are essential for the maintenance of volume homeostasis, and can be of myocardial, renal, and endothelial origin. Advances in peptide engineering have enabled the design of innovative designer NPs that go beyond native peptides in efficacy, specificity, and resistance to enzymatic degradation. Therefore, designer NPs provide an unparalleled opportunity for the treatment of cardiovascular disease. In this review, we report the conceptual framework of peptide engineering of the NPs that resulted in designer peptides for cardiovascular disease. We specifically provide an update on those currently in clinical trials for heart failure and hypertension.

  12. Sinigrin and Its Therapeutic Benefits

    Directory of Open Access Journals (Sweden)

    Anisha Mazumder

    2016-03-01

    Full Text Available Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds.

  13. Therapeutic Versatility of Resveratrol Derivatives.

    Science.gov (United States)

    Nawaz, Waqas; Zhou, Zhongqin; Deng, Sa; Ma, Xiaodong; Ma, Xiaochi; Li, Chuangang; Shu, Xiaohong

    2017-10-29

    Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol to enhance the bioavailability and the pharmacological activity of resveratrol. During the past decades, a large number of natural and synthetic resveratrol derivatives were extensively studied, and the methoxylated, hydroxylated and halogenated derivatives of resveratrol received particular more attention for their beneficial bioactivity. So, in this review, we will summarize the chemical structure and the therapeutic versatility of resveratrol derivatives, and thus provide the related structure activity relationship reference for their practical applications.

  14. Antioxidant attributes of four lamiaceae essential oils

    International Nuclear Information System (INIS)

    Hussain, A.I.; Anwar, A.; Iqbal, T.; Bhatti, I.A.

    2011-01-01

    The present study was conducted to investigate the antioxidant and radical scavenging activities of essential oils of four Lamiaceae plants i.e. Pogostemon cablin, Lavandula angustifolia, Melissa officinalis, and Salvia officinalis native to Pakistan. The essential oil contents from the aerial parts of P. cablin, L. angustifolia, M. officinalis and S. officinalis were found to be 1.98, 0.58, 0.25 and 0.46%, respectively. The principal chemical constituent established in P. cablin L. angustifolia, M. officinalis, and S. officinalis essential oils, were patchouli alcohol, linalool, citronellal, and 1,8-cineol, respectively. The antioxidant activity was evaluated by scavenging of 2,2-diphenyl-1-picryl hydrazyl radical (DPPH), percent inhibition of linoleic acid oxidation and bleaching beta-carotene in linoleic acid system. The essential oils possessed appreciable antioxidant and radical scavenging activities revealing potential for therapeutic applications. (author)

  15. Reviews on Mechanisms of In Vitro Antioxidant Activity of Polysaccharides

    Science.gov (United States)

    Wang, Junqiao; Hu, Shuzhen; Nie, Shaoping; Yu, Qiang; Xie, Mingyong

    2016-01-01

    It is widely acknowledged that the excessive reactive oxygen species (ROS) or reactive nitrogen species (RNS) induced oxidative stress will cause significant damage to cell structure and biomolecular function, directly or indirectly leading to a number of diseases. The overproduction of ROS/RNS will be balanced by nonenzymatic antioxidants and antioxidant enzymes. Polysaccharide or glycoconjugates derived from natural products are of considerable interest from the viewpoint of potent in vivo and in vitro antioxidant activities recently. Particularly, with regard to the in vitro antioxidant systems, polysaccharides are considered as effective free radical scavenger, reducing agent, and ferrous chelator in most of the reports. However, the underlying mechanisms of these antioxidant actions have not been illustrated systematically and sometimes controversial results appeared among various literatures. To address this issue, we summarized the latest discoveries and advancements in the study of antioxidative polysaccharides and gave a detailed description of the possible mechanisms. PMID:26682009

  16. Vaccination with antioxidant enzymes confers protective immunity against challenge infection with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Philip T LoVerde

    2004-08-01

    Full Text Available Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in close contact with host humoral and cellular cytotoxic factors. To establish itself in the host, the parasite has evolved a number of immune evasion mechanisms, such as antioxidant enzymes. Our laboratory has demonstrated that the expression of antioxidant enzymes is developmentally regulated, with the highest levels present in the adult worm, the stage least susceptible to immune elimination, and the lowest levels in the larval stages, the most susceptible to immune elimination. Vaccination of mice with naked DNA constructs containing Cu/Zn cytosolic superoxide dismutase (CT-SOD, signal-peptide containing SOD or glutathione peroxidase (GPX showed significant levels of protection compared to a control group. We have further shown that vaccination with SmCT-SOD but not SmGPX results in elimination of adult worms. Anti-oxidant enzyme vaccine candidates offer an advance over existing vaccine strategies that all seem to target the larval developmental stages in that they target adult worms and thus may have therapeutic as well as prophylactic value. To eliminate the potential for cross-reactivity of SmCT-SOD with human superoxide dismutase, we identified parasite-specific epitope-containing peptides. Our results serve as a basis for developing a subunit vaccine against schistosomiasis.

  17. Therapeutic advances in restless legs syndrome (RLS).

    Science.gov (United States)

    Högl, Birgit; Comella, Cynthia

    2015-09-15

    Levodopa and dopamine agonists have been the main treatment for restless legs syndrome during the past decades. Although their efficacy has been well documented over the short term, long-term dopaminergic treatment is often complicated by augmentation, loss of efficacy, and other side effects. Recent large randomized controlled trials provide new evidence for the efficacy of high-potency opioids and α2δ ligands, and several post hoc analyses, meta-analyses, algorithms, and guidelines have been published, often with a specific focus, for example, on augmentation, or on management of restless legs syndrome during pregnancy. Several new contributions to understanding the pathophysiology of restless legs syndrome have been published, but at this time, whether they will have an impact on treatment possibilities in the future cannot be estimated. © 2015 International Parkinson and Movement Disorder Society.

  18. Biomedical photonics handbook therapeutics and advanced biophotonics

    CERN Document Server

    Vo-Dinh, Tuan

    2014-01-01

    Shaped by Quantum Theory, Technology, and the Genomics RevolutionThe integration of photonics, electronics, biomaterials, and nanotechnology holds great promise for the future of medicine. This topic has recently experienced an explosive growth due to the noninvasive or minimally invasive nature and the cost-effectiveness of photonic modalities in medical diagnostics and therapy. The second edition of the Biomedical Photonics Handbook presents recent fundamental developments as well as important applications of biomedical photonics of interest to scientists, engineers, manufacturers, teachers,

  19. Journal of Phytomedicine and Therapeutics: Advanced Search

    African Journals Online (AJOL)

    Search tips: Search terms are case-insensitive; Common words are ignored; By default only articles containing all terms in the query are returned (i.e., AND is implied); Combine multiple words with OR to find articles containing either term; e.g., education OR research; Use parentheses to create more complex queries; e.g., ...

  20. Selected therapeutic advances beyond the dopaminergic etiologies

    African Journals Online (AJOL)

    Abdelaziz Ghanemi

    2013-04-04

    Apr 4, 2013 ... tive stress14,15 and therefore modify the bioavailability of the neurons.16. To find out more lines of ... including olfactory and memory impairments, sleep abnormal- ities, anxiety and depression, as well ... gic input to the amygdala51,52 and it has been shown that nor- adrenergic and serotonergic systems ...

  1. Novos medicamentos registrados no Brasil: podem ser considerados como avanço terapêutico? New medicines registered in Brazil: can they be considered as a therapeutic advance?

    Directory of Open Access Journals (Sweden)

    Cíntia Maria Gava

    2010-11-01

    Full Text Available Avanços tecnológicos no último século permitiram a descoberta de vários fármacos. Sua introdução, nem sempre com ganhos terapêuticos expressivos e não destituídos de riscos, faz do registro importante momento na avaliação de novos medicamentos. Foi analisado o registro de 49 novos medicamentos pela Agência Nacional de Vigilância Sanitária entre 2000 e 2002 e comercializados no primeiro semestre de 2003, considerando o ganho terapêutico ante os tratamentos existentes. Predominou a produção por empresas americanas (42,9%. A maioria dos medicamentos (63,3% foi classificada como entidade molecular nova, seguindo-se as novas associações (28,6%. Possuíam registro na Food and Drug Administration 75,5% dos medicamentos, sendo possível obter a classificação de sua New Drug Application segundo o potencial terapêutico para 33 medicamentos, dos quais 57,6% foram classificados como padrão. Conclui-se que predomina o registro de medicamentos sem real vantagem terapêutica sobre os já existentes, fato também verdadeiro internacionalmente. São feitas sugestões à Anvisa de forma a estabelecer e divulgar informações quanto à inovação, eficácia e segurança dos novos medicamentos, já que são importantes para o consumidor, os profissionais de saúde e os gestores.Technological advances in the last century led to the discovery of a variety of medicines. Their introduction, not always with significant therapeutic gains and not without risk, made the register by regulatory agency an important moment in their evaluation. The aim of this study was to analyze 49 new medicines registered by the National Health Surveillance Agency (Anvisa, between the years 2000 and 2002 and commercialized in the first half of 2003, considering their therapeutic advantage. Most medicines (42.9% were from the American pharmaceutical industry. Most of them (63.3% were classified as a new molecular entity, followed by the new fixed dose combinations (28

  2. The Role of Oxidative Stress and Antioxidants in Liver Diseases.

    Science.gov (United States)

    Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

    2015-11-02

    A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  3. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Sha Li

    2015-11-01

    Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  4. Skewed Epigenetics: An Alternative Therapeutic Option for Diabetes Complications

    Directory of Open Access Journals (Sweden)

    Gabriele Togliatto

    2015-01-01

    Full Text Available Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called “metabolic memory.”

  5. Delivery aspects of antioxidants in diabetes management.

    Science.gov (United States)

    Duvvuri, Lakshmi Sailaja; Katiyar, Sameer; Kumar, Ashutosh; Khan, Wahid

    2015-05-01

    Ample research has been done to study the role of oxidative stress due to the generation of excess reactive species in initiation and progression of diabetic complications. A positive result has been indicated hypothesizing that abating this oxidative stress can prove to be an alternate strategy in therapy apart from oral antidiabetic drugs. But these dietary antioxidants are less efficient because of poor solubility, permeability, instability on storage, gastrointestinal degradation and first-pass metabolism. This review gives a brief insight into the molecular mechanism of oxidative stress in development of diabetic complications. Major hurdles limiting the translation of antioxidants to clinical area are also discussed. Various delivery approaches including both conventional and novel drug delivery systems explored so far for combating these challenges in antioxidant delivery are also explored. Mitochondrial targeting of such molecules is also briefly discussed. A thorough study of clinical efficacy and safety of antioxidants on long-term use judging its clinical applicability is required. The clinical success of antioxidants as a therapeutic strategy involves a combination of effective design of drug delivery carrier that are in turn related to their degradation profile, possibility of cellular uptake at defined site of action and so on and clinical and preclinical trials that will provide a base for the design of dose and administration regimen.

  6. Nutraceutical Antioxidants as Novel Neuroprotective Agents

    Directory of Open Access Journals (Sweden)

    Daniel A. Linseman

    2010-11-01

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

  7. Antioxidants of Edible Mushrooms.

    Science.gov (United States)

    Kozarski, Maja; Klaus, Anita; Jakovljevic, Dragica; Todorovic, Nina; Vunduk, Jovana; Petrović, Predrag; Niksic, Miomir; Vrvic, Miroslav M; van Griensven, Leo

    2015-10-27

    Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality.

  8. Antioxidants of Edible Mushrooms

    Directory of Open Access Journals (Sweden)

    Maja Kozarski

    2015-10-01

    Full Text Available Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality.

  9. ANTIOXIDANT SUPPLEMENTATION IN THE TREATMENT OF AGING-ASSOCIATED DISEASES

    Directory of Open Access Journals (Sweden)

    Valeria eConti

    2016-02-01

    Full Text Available Oxidative stress is generally considered an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of the antioxidants supplementation therapy that might partially depend, among others, from an underestimation of the patient specific metabolic demand and genetic background, are presented.

  10. Therapeutic misadventure.

    Science.gov (United States)

    Langford, N J

    2010-10-01

    Therapeutic misadventure can be defined as an injury or an adverse event caused by medical management rather than by an underlying disease. Within the National Health Service there were over 86,000 reported adverse incidents in 2007. In the USA medication errors have been rated as the fourth highest cause of death. Unfortunately one of the greatest contributors to iatrogenic injury is human error. The potential types of misadventure are infinite. Medication errors are a major part of this, being responsible for over 70% of cases that cause serious harm. However, many medication errors caused by slips, lapses, technical errors and mistakes are preventable; intentional violations of safe operating procedures are not. While medication errors were tolerated by society in the past, the readiness to institute criminal proceedings against health-care professionals has increased greatly in the UK over the last decade. The medication process consists of writing prescriptions, dispensing the product, administering it and monitoring its effects. Prescription errors arise owing to incomplete information, lack of appropriate labelling, environmental factors and human blunders. Even with a perfect prescription the right medication must be dispensed and appropriately labelled. Dispensing errors are not uncommon and may be compounded by non-clinical considerations. Administration of a drug by injection is one of the most dangerous aspects of the medication process, especially in inexperienced hands. The final component of medication supply is monitoring the effect of the medication. With short courses of medication such monitoring is easy, but with long-term medication, particularly with potent drugs where the margin between efficacy and toxicity is small, active procedures may be required to ensure toxicity does not ensue. Despite the endeavour of health-care professions to stick to the rule of 'first, do no harm', in reality this is difficult to achieve all of the time. When

  11. The Quest for Selective Nox Inhibitors and Therapeutics: Challenges, Triumphs and Pitfalls

    Science.gov (United States)

    Cifuentes-Pagano, Eugenia; Meijles, Daniel N.

    2014-01-01

    Abstract Significance: Numerous studies in animal models and human subjects corroborate that elevated levels of reactive oxygen species (ROS) play a pivotal role in the progression of multiple diseases. As a major source of ROS in many organ systems, the NADPH oxidase (Nox) has become a prime target for therapeutic development. Recent Advances: In recent years, intense efforts have been dedicated to the development of pan- and isoform-specific Nox inhibitors as opposed to antioxidants that proved ineffective in clinical trials. Over the past decade, an array of compounds has been proposed in an attempt to fill this void. Critical Issues: Although many of these compounds have proven effective as Nox enzyme family inhibitors, isoform specificity has posed a formidable challenge to the scientific community. This review surveys the most prominent Nox inhibitors, and discusses potential isoform specificity, known mechanisms of action, and shortcomings. Some of these inhibitors hold substantial promise as targeted therapeutics. Future Directions: Increased insight into the mechanisms of action and regulation of this family of enzymes as well as atomic structures of key Nox subunits are expected to give way to a broader spectrum of more potent, efficacious, and specific molecules. These lead molecules will assuredly serve as a basis for drug development aimed at treating a wide array of diseases associated with increased Nox activity. Antioxid. Redox Signal. 20, 2741–2754. PMID:24070014

  12. Antioxidants of edible mushrooms

    NARCIS (Netherlands)

    Kozarski, Maja; Klaus, Anita; Jakovljevic, Dragica; Todorovic, Nina; Vunduk, Jovana; Petrović, Predrag; Niksic, Miomir; Vrvic, Miroslav M.; Griensven, Van Leo

    2015-01-01

    Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic

  13. Antioxidant plants and diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hamid Nasri

    2015-01-01

    Full Text Available The incidence of diabetes mellitus (DM is increasing rapidly and it is expected to increase by 2030. Other than currently available therapeutic options, there are a lot of herbal medicines, which have been recommended for its treatment. Herbal medicines have long been used for the treatment of DM because of the advantage usually having no or less side-effects. Most of these plants have antioxidant activities and hence, prevent or treat hard curable diseases, other than having the property of combating the toxicity of toxic or other drugs. In this review other than presenting new findings of DM, the plants, which are used and have been evaluated scientifically for the treatment of DM are introduced.

  14. Antioxidant and antimicrobial activities of native Rosa sp. from British Columbia, Canada.

    Science.gov (United States)

    Yi, Ocksook; Jovel, Eduardo M; Towers, G H Neil; Wahbe, Tanya R; Cho, Dongwuk

    2007-05-01

    Indigenous traditional knowledge and western science have revealed the potential for significant nutritional and therapeutic benefits among natural antioxidants. We investigated antioxidant and antimicrobial activity of rose hip extracts (Rosa nutkana, Rosa pisocarpa and Rosa woodsii) from wild British Columbia populations using liposome oxidation and disc diffusion assays. All extracts exhibited strong antioxidant activity. R. nutkana pericarp extracts contained high phenolic concentrations and showed greater antioxidant and antimicrobial activity than seed extracts. R. woodsii seed extracts had a higher phenolic concentration and greater antioxidant activity than pericarp extracts. Antioxidant activity was correlated with antimicrobial activity, and both extracts showed antimicrobial activity against yeast and Gram-positive bacteria. Our study is the first to demonstrate the antioxidant and antimicrobial properties of wild British Columbia roses. The effectiveness of selected species compared with standards demonstrates the significance of this natural resource to the continued health of human populations, and the need for conservation practices.

  15. Screening of dietary antioxidants against mitochondria-mediated oxidative stress by visualization of intracellular redox state.

    Science.gov (United States)

    Maharjan, Sunita; Sakai, Yasuyoshi; Hoseki, Jun

    2016-01-01

    Mitochondrial impairment and the resulting generation of reactive oxygen species (ROS) have been associated with aging and its related pathological conditions. Recently, dietary antioxidants have gained significant attention as potential preventive and therapeutic agents against ROS-generated aging and pathological conditions. We previously demonstrated that food-derived antioxidants prevented intracellular oxidative stress under proteasome inhibition conditions, which was attributed to mitochondrial dysfunction and ROS generation, followed by cell death. Here, we further screened dietary antioxidants for their activity as redox modulators by visualization of the redox state using Redoxfluor, a fluorescent protein redox probe. Direct alleviation of ROS by antioxidants, but not induction of antioxidative enzymes, prevented mitochondria-mediated intracellular oxidation. The effective antioxidants scavenged mitochondrial ROS and suppressed cell death. Our study indicates that redox visualization under mitochondria-mediated oxidative stress is useful for screening potential antioxidants to counteract mitochondrial dysfunction, which has been implicated in aging and the pathogenesis of aging-related diseases.

  16. Chemical composition, antioxidant and anti-AGEs activities of a French poplar type propolis.

    Science.gov (United States)

    Boisard, Séverine; Le Ray, Anne-Marie; Gatto, Julia; Aumond, Marie-Christine; Blanchard, Patricia; Derbré, Séverine; Flurin, Catherine; Richomme, Pascal

    2014-02-12

    Accumulation in tissues and serum of advanced glycation end-products (AGEs) plays an important role in pathologies such as Alzheimer's disease or, in the event of complications of diabetes, atherosclerosis or renal failure. Therefore, there is a potential therapeutic interest in compounds able to lower intra and extracellular levels of AGEs. Among them, natural antioxidants (AO) with true anti-AGEs capabilities would represent good candidates for development. The purpose of this study was to evaluate the AO and anti-AGEs potential of a propolis batch and then to identify the main compounds responsible for these effects. In vivo, protein glycation and oxidative stress are closely related. Thus, AO and antiglycation activities were evaluated using both DPPH and ORAC assays, respectively, as well as a newly developed automated anti-AGEs test. Several propolis extracts exhibited very good AO and anti-AGEs activities, and a bioguided fractionation allowed us to identify pinobanksin-3-acetate as the most active component.

  17. Potential therapeutic applications of biosurfactants.

    Science.gov (United States)

    Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

    2013-12-01

    Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Antioxidants Protect against Arsenic Induced Mitochondrial Cardio-Toxicity

    Directory of Open Access Journals (Sweden)

    Clare Pace

    2017-12-01

    Full Text Available Arsenic is a potent cardiovascular toxicant associated with numerous biomarkers of cardiovascular diseases in exposed human populations. Arsenic is also a carcinogen, yet arsenic trioxide is used as a therapeutic agent in the treatment of acute promyelotic leukemia (APL. The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. Many of the toxic effects of arsenic are mediated by mitochondrial dysfunction and related to arsenic’s effect on oxidative stress. Therefore, we investigated the effectiveness of antioxidants against arsenic induced cardiovascular dysfunction. A growing body of evidence suggests that antioxidant phytonutrients may ameliorate the toxic effects of arsenic on mitochondria by scavenging free radicals. This review identifies 21 antioxidants that can effectively reverse mitochondrial dysfunction and oxidative stress in cardiovascular cells and tissues. In addition, we propose that antioxidants have the potential to improve the cardiovascular health of millions of people chronically exposed to elevated arsenic concentrations through contaminated water supplies or used to treat certain types of leukemias. Importantly, we identify conceptual gaps in research and development of new mito-protective antioxidants and suggest avenues for future research to improve bioavailability of antioxidants and distribution to target tissues in order reduce arsenic-induced cardiovascular toxicity in a real-world context.

  19. Antioxidative phytoceuticals to ameliorate pancreatitis in animal models: An answer from nature

    Science.gov (United States)

    Park, Jong-Min; Lee, Sooyeon; Chung, Mi Kyung; Kwon, Sung-Hun; Kim, Eun-Hee; Ko, Kwang Hyun; Kwon, Chang Il; Hahm, Ki Baik

    2014-01-01

    Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis (SAP), the disease remains without a specific therapy to be executed within the first hours to days after onset of symptoms. Although earlier management for SAP should aim to either treat organ failure or reduce infectious complications, the current standard of care for the general management of AP in the first hours to days after onset of symptoms include intravenous fluid replacement, nutritional changes, and the use of analgesics with a close monitoring of vital signs. Furthermore, repeated evaluation of severity is very important, as the condition is particularly unstable in the early stages. In cases where biliary pancreatitis is accompanied by acute cholangitis or in cases where biliary stasis is suspected, an early endoscopic retrograde cholangiopancreatography is recommended. However, practice guidelines regarding the treatment of pancreatitis are suboptimal. In chronic pancreatitis, conservative management strategies include lifestyle modifications and dietary changes followed by analgesics and pancreatic enzyme supplementation. Recently, attention has been focused on phytoceuticals or antioxidants as agents that could surpass the limitations associated with currently available therapies. Because oxidative stress has been shown to play an important role in the pathogenesis of pancreatitis, antioxidants alone or combined with conventional therapy may improve oxidative-stress-induced organ damage. Interest in phytoceuticals stems from their potential use as simple, accurate tools for pancreatitis prognostication that could replace older and more tedious methods. Therefore, the use of antioxidative nutrition or phytoceuticals may represent a new direction for clinical research in pancreatitis. In this review article, recent advances in the understanding of the pathogenesis of pancreatitis are

  20. Antioxidative properties of flavonoids

    NARCIS (Netherlands)

    Bowedes, T.C.F.; Luttikhold, J.; Stijn, van M.F.M.; Visser, M.; Norren, van K.; Vermeulen, M.A.R.; Leeuwen, P.A.M.

    2011-01-01

    Evidence accumulates that a family of plant compounds, known as flavonoids, can prevent or slow down the progression of cardiovascular diseases, cancer, inflammatory and neurodegenerative diseases. Flavonoids are considered beneficial, this is often attributed to their powerful antioxidant

  1. Atmospheric oxidation and antioxidants

    CERN Document Server

    Meurant, Gerard

    1993-01-01

    Volume I reviews current understanding of autoxidation, largely on the basis of the reactions of oxygen with characterised chemicals. From this flows the modern mechanism of antioxidant actions and their application in stabilisation technology.

  2. Comparative profiling of biomarker psoralen in antioxidant active ...

    African Journals Online (AJOL)

    Comparative profiling of biomarker psoralen in antioxidant active extracts of different species of genus Ficus by validated HPTLC method. ... an important tool to assure the therapeutic dose of active ingredients in herbal formulations as well as for standardization and quality control of bulk drugs and in-process formulations.

  3. Evaluation of Antioxidant and Anti-neuroinflammatory Activities of ...

    African Journals Online (AJOL)

    ... NF-κB activation in LPS-stimulated BV-2 cells. Conclusion: HFE can be considered as a useful therapeutic and preventive approach for the treatment of neurodegenerative diseases and oxidative stress-related diseases. Keywords: Hizikia fusiforme, Antioxidant activity, Anti-neuroinflammation activity, Inducible nitric oxide ...

  4. Evaluation of Antioxidant and Antifungal Activities of Polyphenol-rich ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antioxidant and antifungal activities of polyphenol-rich extracts of the dried fruit pulp of Garcinia pedunculata (GP) and Garcinia morella (GM) to determine their traditional claims of therapeutic activity against certain diseases. Methods: Analysis of total phenolic (TP) and flavonoid (TF) contents of the ...

  5. Plasma antioxidants from chocolate

    OpenAIRE

    Serafini, M.; Bugianesi, R.; Maiani, G.; Valtuena, S.; De Santis, S.; Crozier, A.

    2003-01-01

    There is some speculation that dietary flavonoids from chocolate, in particular (-)epicatechin, may promote cardiovascular health as a result of direct antioxidant effects or through antithrombotic mechanisms. Here we show that consumption of plain, dark chocolate results in an increase in both the total antioxidant capacity and the (-)epicatechin content of blood plasma, but that these effects are markedly reduced when the chocolate is consumed with milk or if milk is incorporated as milk ch...

  6. Antioxidant supplements and mortality

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Christian

    2014-01-01

    Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high-income countries. This has stimulated interest in the preventive potential of a...... of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging....

  7. Antioxidants in Translational Medicine.

    Science.gov (United States)

    Schmidt, Harald H H W; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis; Daiber, Andreas; Cuadrado, Antonio

    2015-11-10

    It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities.

  8. Antioxidant Capacity and Antimutagenic Potential of Murraya koenigii

    Directory of Open Access Journals (Sweden)

    Maryam Zahin

    2013-01-01

    Full Text Available It is well known that the intake of antioxidants with increased consumption of fruits and vegetables and medicinal herbs contributes towards reduced risk of certain diseases including cancers. This study aims to evaluate the broad-spectrum antioxidant and antimutagenic activities as well as to elucidate phytochemical profile of an Indian medicinal plant Murraya koenigii (curry leaves. Leaves of the plant were successively fractionated in various organic solvents. Benzene fraction demonstrated the highest phenolic content followed by petroleum ether. The benzene fraction showed maximum antioxidant activity in all tested assays, namely, phosphomolybdenum, 2,2-diphenyl-1-picrylhydrazyl (DPPH free radical, ferric reducing antioxidant power (FRAP and cupric reducing antioxidant capacity (CUPRAC assays. Based on the promising broad-spectrum antioxidant activity, benzene fraction was further evaluated for antimutagenic activity and showed a dose-dependent antimutagenic response in Ames Salmonella mutagenicity assay. It inhibited 72–86% mutagenicity induced by sodium azide, methyl methanesulfonate, benzo(apyrene, and 2-aminoflourene at the maximum tested concentration (100 μg/mL in Salmonella typhimurium tester strains. At least 21 compounds were detected by GC/MS. The findings clearly demonstrated that phenolic-rich benzene fraction has promising broad-spectrum antioxidant and antimutagenic property and needs further evaluation to exploit its therapeutic potential.

  9. Antioxidant potential of selected Spirulina platensis preparations.

    Science.gov (United States)

    Dartsch, Peter C

    2008-05-01

    Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and therapeutic properties and is also capable of acting as an antioxidant and antiinflammatory agent. In this study, a cell-free and a cell-based test assay were used to examine the antioxidant and antiinflammatory properties of four selected Spirulina platensis preparations: (1) Biospirulina, (2) SpiruComplex, a preparation with naturally bound selenium, chromium and zinc, (3) SpiruZink, a preparation with naturally bound zinc, (4) Zinkspirulina + Acerola, a preparation with naturally bound zinc and acerola powder. The cell-free test assay used potassium superoxide as a donor for superoxide radicals, whereas the cell-based test assay used the formation of intracellular superoxide radicals of functional neutrophils upon stimulation by phorbol-12-myristate-13-acetate as a model to investigate the potential of Spirulina preparations to inactivate superoxide radicals. In accordance with the recommended daily dosage, test concentrations ranging from 50 to 1000 microg/mL were chosen. The results showed a dose-dependent inactivation of free superoxide radicals (antioxidant effect) as well as an antiinflammatory effect characterized by a dose-dependent reduction of the metabolic activity of functional neutrophils and a dose-dependent inactivation of superoxide radicals generated during an oxidative burst. The results demonstrate that the tested Spirulina preparations have a high antioxidant and antiinflammatory potential. Especially SpiruZink and Zinkspirulina + Acerola might be useful as a supportive therapeutic approach for reducing oxidative stress and/or the generation of oxygen radicals in the course of inflammatory processes.

  10. Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products.

    Science.gov (United States)

    Maeda, Sayaka; Matsui, Takanori; Ojima, Ayako; Takeuchi, Masayoshi; Yamagishi, Sho-Ichi

    2014-09-01

    Advanced glycation end products (AGEs) not only inhibit DNA synthesis but also play a role in diabetic retinopathy by evoking apoptosis and inflammation in retinal pericytes via interaction with a receptor for AGE (RAGE). Similarly, sulforaphane, which is a naturally occurring isothiocyanate that is found in widely consumed cruciferous vegetables, protects against oxidative stress-induced tissue damage. Therefore, we hypothesized that sulforaphane could inhibit AGE-induced pericytes injury through its antioxidative properties. Advanced glycation end product stimulated superoxide generation as well as RAGE gene and protein expression in bovine-cultured retinal pericytes, and these effects were prevented by the treatment with sulforaphane. Antibodies directed against RAGE also blocked AGE-evoked reactive oxygen species generation in pericytes. Sulforaphane and antibodies directed against RAGE significantly inhibited the AGE-induced decrease in DNA synthesis, apoptotic cell death, and up-regulation of monocyte chemoattractant protein 1 messenger RNA levels in pericytes. For the first time, the present study demonstrates that sulforaphane could inhibit DNA synthesis, apoptotic cell death, and inflammatory reactions in AGE-exposed pericytes, partly by suppressing RAGE expression via its antioxidative properties. Blockade of the AGE-RAGE axis in pericytes by sulforaphane might be a novel therapeutic target for the treatment of diabetic retinopathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Macrophage antioxidant protection within atherosclerotic plaques.

    Science.gov (United States)

    Gieseg, Steven P; Leake, David S; Flavall, Elizabeth M; Amit, Zunika; Reid, Linzi; Yang, Ya-Ting

    2009-01-01

    Macrophage cells within inflammatory lesions are exposed to a wide range of degrading and cytotoxic molecules including reactive oxygen species. Unlike neutrophils, macrophages do not normally die in this environment but continue to generate oxidants, phagocytose cellular remains, and release a range of cyto-active agents which modulate the immune response. It is this potential of the macrophage cell to survive in an oxidative environment that allows the growth and complexity of advanced atherosclerotic plaques. This review will examine the oxidants encountered by macrophages within an atherosclerotic plaque and describe some of the potential antioxidant mechanisms which enable macrophages to function within inflammatory lesions. Ascorbate, a-tocopherol, and glutathione appear to be central to the protection of macrophages yet additional antioxidant mechanisms appear to be involved. Gamma-Interferon causes macrophages to generate 7,8-dihydroneopterin, neopterin and 3-hydroxyanthranilic acid both of which have antioxidant properties. Manganese superoxide dismutase is also upregulated in macrophages. The evidence that these antioxidants provide further protection, so allowing the macrophage cells to survive within sites of chronic inflammation such as atherosclerotic plaques, will be described.

  12. Antioxidant and Antioxidant capacity of raw and processed Nigerian ...

    African Journals Online (AJOL)

    Lechner,2010;. Zhang et al., 2013) and hepatoprotective effects. (Rabeh, 2015). This study was carried out to investigate the antioxidant and antioxidant capacity of raw and processed Nigerian red Beetroots for its potential as a functional food.

  13. The antioxidant master glutathione and periodontal health

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Bains

    2015-01-01

    Full Text Available Glutathione, considered to be the master antioxidant (AO, is the most-important redox regulator that controls inflammatory processes, and thus damage to the periodontium. Periodontitis patients have reduced total AO capacity in whole saliva, and lower concentrations of reduced glutathione (GSH in serum and gingival crevicular fluid, and periodontal therapy restores the redox balance. Therapeutic considerations for the adjunctive use of glutathione in management of periodontitis, in limiting the tissue damage associated with oxidative stress, and enhancing wound healing cannot be underestimated, but need to be evaluated further through multi-centered randomized controlled trials.

  14. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Science.gov (United States)

    Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

    2013-01-01

    Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage. PMID:23936799

  15. Free radicals, oxidative stress and importance of antioxidants in human health

    Directory of Open Access Journals (Sweden)

    K.I. Priyadarsini

    2011-07-01

    Full Text Available Reactive oxygen species (ROS is a collective term used for oxygen containing free radicals, depending on their reactivity and oxidizing ability. ROS participate in a variety of chemical reactions with biomolecules leading to a pathological condition known as oxidative stress. Antioxidants are employed to protect biomolecules from the damaging effects of such ROS. In the beginning, antioxidant research was mainly aimed at understanding free radical reactions of ROS with antioxidants employing biochemical assays and kinetic methods. Later on, studies began to be directed to monitor the ability of anti-oxidants to modulate cellular signaling proteins like receptors, secondary messengers, transcription factors, etc. Of late several studies have indicated that antioxidants can also have deleterious effects on human health depending on dosage and bio-availability. It is therefore, necessary to validate the utility of antioxidants in improvement of human health in order to take full advantage of their therapeutic potential.

  16. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  17. The renaissance of complement therapeutics.

    Science.gov (United States)

    Ricklin, Daniel; Mastellos, Dimitrios C; Reis, Edimara S; Lambris, John D

    2018-01-01

    The increasing number of clinical conditions that involve a pathological contribution from the complement system - many of which affect the kidneys - has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond.

  18. The renaissance of complement therapeutics

    Science.gov (United States)

    Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

    2018-01-01

    The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277

  19. Renoprotective effect of the antioxidant curcumin: Recent findings

    Directory of Open Access Journals (Sweden)

    Joyce Trujillo

    2013-01-01

    Full Text Available For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2, inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.

  20. [Therapeutic Aggressiveness and Liquid Oncology].

    Science.gov (United States)

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  1. Recent advances in radiopharmaceuticals

    International Nuclear Information System (INIS)

    Smith, S.

    2000-01-01

    Full text: Radiopharmaceuticals in Nuclear Medicine may be divided into diagnostic and therapeutic agents. The diagnostic area is perceived to be mature, while the therapeutic side of nuclear medicine is still evolving. There are over 100 diagnostic radiopharmaceutical products available, the greatest number applied in cardiology followed by oncology and neurology. The greatest success in therapeutic nuclear medicine has been achieved in thyroid cancer, hyperthyroidism and bone pain palliation. Those in the field believe the future of nuclear medicine resides in the growth potential of the emerging therapeutic market, hence much of the recent research has been focussed in the development of therapeutic agents for targeting cancers. Radiopharmaceuticals under development or in clinical trials involve the use of radionuclides such as Y-90, Pd-103, Ir-192, Re-188, I-131, Sm-153, Sn-114, Sr-90, Cu-64 and In-111. Advances in cyclotron and camera technology as well as automation has enhanced and widened the potential use of positron emitting radiopharmaceuticals such as F-18 Fluorodeoxyglucose (FDG). However the relationship between FDG uptake and glucose consumption in normal and diseased tissue is still to be defined. Many challenges remain for the nuclear medicine community to apply new knowledge of human biochemistry in the development of new radiopharmaceuticals. A better understanding of effects of radiation and its role in the design of therapeutic agents is undoubtedly pivotal for advancing therapeutic Nuclear Medicine into the future

  2. Resveratrol as a Potential Therapeutic Candidate for the Treatment and Management of Alzheimer's Disease.

    Science.gov (United States)

    Braidy, Nady; Jugder, Bat-Erdene; Poljak, Anne; Jayasena, Tharusha; Mansour, Hussein; Nabavi, Seyed Mohammad; Sachdev, Perminder; Grant, Ross

    2016-01-01

    Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical present in red wine, grapes, berries, chocolate and peanuts. Clinically, resveratrol has exhibited significant antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties. Although resveratrol was first isolated in 1940, it was not until the last decade that it was recognised for its potential therapeutic role in reducing the risk of neurodegeneration, and Alzheimer's disease (AD) in particular. AD is the primary cause of progressive dementia. Resveratrol has demonstrated neuroprotective effects in several in vitro and in vivo models of AD. Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that resveratrol also facilitates non-amyloidogenic breakdown of the amyloid precursor protein (APP), and promotes removal of neurotoxic amyloid beta (Aβ) peptides, a critical step in preventing and slowing down AD pathology. Resveratrol also reduces damage to neuronal cells via a variety of additional mechanisms, most notably is the activation of NAD(+)-dependent histone deacetylases enzymes, termed sirtuins. However in spite of the considerable advances in clarifying the mechanism of action of resveratrol, it is unlikely to be effective as monotherapy in AD due to its poor bioavailability, biotransformation, and requisite synergism with other dietary factors. This review summarizes the relevance of resveratrol in the pathophysiology of AD. It also highlights why resveratrol alone may not be an effective single therapy, and how resveratrol coupled to other compounds might yet prove an effective therapy with multiple targets.

  3. Antioxidants for female subfertility.

    Science.gov (United States)

    Showell, Marian G; Mackenzie-Proctor, Rebecca; Jordan, Vanessa; Hart, Roger J

    2017-07-28

    A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2016) with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, the Cochrane Central Register of Studies (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of appropriate studies and searched for ongoing trials in the clinical trials registers. We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We pooled studies using a fixed-effect model, and calculated odds ratios (ORs) with 95% confidence intervals (CIs) for the dichotomous

  4. Antioxidant, anti-alpha-glucosidase and pancreatic beta-cell protective effects of methanolic extract of Ensete superbum Cheesm seeds

    Directory of Open Access Journals (Sweden)

    Solomon Habtemariam

    2017-02-01

    Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic β-cell protection.

  5. Topical applied nutraceutical antioxidant formulation reduces ocular oxidative stress

    Directory of Open Access Journals (Sweden)

    Peter F. Kador

    2017-01-01

    Full Text Available Oral nutraceutical antioxidants have shown disappointing clinical results in reducing oxidation-induced age-related cataract and other ocular diseases.Based on the hypothesis that nutraceuticals do not adequately reach the lens by oral administration, we have developed a unique topical antioxidant formulation whose active ingredients have the reported ability to reduce oxidative stress through free radical scavenging and chelating activity. This topical nutraceutical formulation was designed to mimic the in vivo activity of multifunctional antioxidants, compoundswhich arebeing developed in our laboratory toindependently scavenge free radicals and selectively bind redox metals.A comparison of the efficacy of this topical nutraceutical to multifunctional antioxidants in laboratory animal models of oxidation-induced lens changes, retinal changes,and dry eye is reviewed.Although it is less potent than the small molecule multifunctional antioxidants that will require FDA approval, the topical nutraceutical formulation beneficially reduces ocular oxidative stress.These studies suggest that this topical antioxidant may fill an unmet therapeutic need by providing a nutraceutical that beneficially reduces the effects of oxidation on age-related ocular diseases

  6. PHYTOCHEMICAL ANALYSIS, ANTIOXIDANT AND ...

    African Journals Online (AJOL)

    2012-12-31

    EC50 in μg/ml) and total antioxidant activity (mg GAE/g DW) power Phoenyx dactylifera leaves extract and anthentic standards (BHT in IC50, BHA and chlorogenic acid in EC50 μg/ml). Plant species and standards. DPPH test.

  7. Antioxidants: real medicines?

    African Journals Online (AJOL)

    Repro

    While endogenous metabolic pathways utilise oxidative processes largely for our benefit, various pathological .... quenchers of these oxidants have been discovered and characterised. Endogenous antioxidants may be ... ly recognised, what is much less well known is the fact that vitamin. E is a family of 8 vitamins: 4 toco-.

  8. Antioxidant effects of carotenoids

    NARCIS (Netherlands)

    Bast, A.; Haenen, G.R.M.M.; Berg, R. van den; Berg, H. van den

    1998-01-01

    Surprisingly, neither the precise pharmacological effect nor the toxicological profile is usually established for food components. Carotenoids are no exception in this regard. Only limited insight into the pharmacology and toxicology of carotenoids exists. It is known that the antioxidant action of

  9. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    Science.gov (United States)

    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.

  10. Delayed Posthypoxic Leukoencephalopathy: Improvement with Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Franklin King

    2015-12-01

    Full Text Available Introduction: Delayed posthypoxic leukoencephalopathy (DPHL may result from a variety of hypoxic insults, including respiratory depression from an opiate overdose. The underlying pathophysiological mechanism of DPHL remains uncertain. We describe a patient with a typical case of DPHL who responded clinically to antioxidant treatment. Methods: Clinical, serological, and radiographic investigations were undertaken in the evaluation of the patient. Results: A 63-year-old man developed altered mental status 10 days following recovery from an opiate overdose and aspiration pneumonia that required intubation. The clinical course and brain imaging were consistent with DPHL. Initiation of antioxidant therapy with vitamin E, vitamin C, B-complex vitamins, and coenzyme Q10 coincided with the prompt reversal of clinical deterioration. Conclusions: The potential therapeutic effect of antioxidants on DPHL needs to be explored in future cases. If this relationship indeed holds true, it would be consistent with the hypothesis that formation of reactive oxygen species during reperfusion plays a role in the pathophysiology of this disorder.

  11. Are Antioxidants a Potential Therapy for FSHD? A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Adam Philip Denny

    2017-01-01

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an inherited myopathy affecting approximately 1 in 7500 individuals worldwide. It is a progressive disease characterised by skeletal muscle weakness and wasting. A genetic mutation on the 4q35 chromosome results in the expression of the double homeobox 4 gene (DUX4 which drives oxidative stress, inflammation, toxicity, and atrophy within the skeletal muscle. FSHD is characterised by oxidative stress, and there is currently no cure and a lack of therapies for the disease. Antioxidants have been researched for many years, with investigators aiming to use antioxidants therapeutically for oxidative stress-associated diseases. This has included both natural and synthetic antioxidants. The use of antioxidants in preclinical or clinical models has been largely successful with a plethora of research reporting positive results. However, when translated to clinical trials, the use of antioxidants as a therapeutic intervention for a variety of disease has been largely unsuccessful. Moreover, specifically focusing on FSHD, limited research has been conducted on the use of antioxidants as a therapy in either preclinical or clinical models. This review summarises the current state of antioxidant use in the treatment of FSHD and discusses their potential avenue for therapeutic use for FSHD patients.

  12. Novel Therapeutics for Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Lowery, Maeve A; O'Reilly, Eileen M

    2015-08-01

    The last decade has seen significant developments in the use of combination systemic therapy for advanced pancreatic ductal adenocarcinoma (PDAC), with median survival approaching 1 year for select patients treated with FOLFIRINOX in the metastatic setting. However, it is sobering that these developments have been achieved with the use of traditional cytotoxics rather than from successes in the more modern fields of molecularly targeted therapies or immunotherapy. This article highlights several promising therapeutic approaches to PDAC currently under clinical evaluation, including immune therapies, molecularly targeted therapies, strategies for stromal depletion, and targeted therapy for genetically selected patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Polyphenols, Antioxidants and the Sympathetic Nervous System.

    Science.gov (United States)

    Bruno, Rosa Maria; Ghiadoni, Lorenzo

    2017-11-14

    A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity and metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympatho-excitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel

  14. Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Mark A. Babizhayev

    2016-12-01

    Mitochondrial targeting of compounds with universal types of antioxidant activity represents a promising approach for treating a number of ROS-related ocular diseases of the aging eye and can be implicated in the management of cataracts and primary open-angle glaucoma.

  15. "Lycopene: A Promising Antioxidant"

    Directory of Open Access Journals (Sweden)

    Anshumalee Nisheeth

    2007-01-01

    Full Text Available Lycopene is a red colored fat soluble carotenoid, which gives tomatoes and several other fruits their deep red colour. It has shown potential role in prevention and cure of various systemic and oral diseases including malignancies due to its antioxidant and other cancer preventing properties. Lycopene with its 11 conjugated and 2 non conjugated double bonds is the most efficient singIet oxygen quencher and is considered most potent antioxidant among carotenoids. It has shown to be efficient in the management of oral cancer and precancer like leukoplakia and has shown the potential in the management of other oral mucosal lesions thought to arise due to free radical onslaught such as oral lichen planes.

  16. Antioxidants in dermatology*

    Science.gov (United States)

    Addor, Flavia Alvim Sant'anna

    2017-01-01

    The skin cells continuously produce, through cellular respiration, metabolic processes or under external aggressions, highly reactive molecules oxidation products, generally called free radicals. These molecules are immediately neutralized by enzymatic and non-enzymatic systems in a physiological and dynamic balance. In situations where this balance is broken, various cellular structures, such as the cell membrane, nuclear or mitochondrial DNA may suffer structural modifications, triggering or worsening skin diseases. several substances with alleged antioxidant effects has been offered for topical or oral use, but little is known about their safety, possible associations and especially their mechanism of action. The management of topical and oral antioxidants can help dermatologist to intervene in the oxidative processes safely and effectively, since they know the mechanisms, limitations and potential risks of using these molecules as well as the potential benefits of available associations. PMID:29186248

  17. Enzyme therapeutics for systemic detoxification.

    Science.gov (United States)

    Liu, Yang; Li, Jie; Lu, Yunfeng

    2015-08-01

    Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Mustard Gas Inhalation Injury: Therapeutic Strategy.

    Science.gov (United States)

    Keyser, Brian M; Andres, Devon K; Holmes, Wesley W; Paradiso, Danielle; Appell, Ashley; Letukas, Valerie A; Benton, Betty; Clark, Offie E; Gao, Xiugong; Ray, Prabhati; Anderson, Dana R; Ray, Radharaman

    2014-07-01

    Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies using the other drugs, that is, anti-inflammatory, antioxidant, and protease inhibitor compounds. © The Author(s) 2014.

  19. Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts.

    Science.gov (United States)

    Karasu, Cimen; Cumaoğlu, Ahmet; Gürpinar, Ali Rifat; Kartal, Murat; Kovacikova, Lucia; Milackova, Ivana; Stefek, Milan

    2012-03-01

    The pomegranate, Punica granatum L., has been the subject of current interest as a medicinal agent with wide-ranging therapeutic indications. In the present study, pomegranate ethanolic seed and hull extracts were tested, in comparison with a commercial sample, for the inhibition of aldose reductase, an enzyme involved in the etiology of diabetic complications. In vitro inhibition of rat lens aldose reductase was determined by a conventional method. Pomegranate ethanolic hull extract and commercial pomegranate hull extract exhibited similar aldose reductase inhibitory activity characterized by IC(50) values ranging from 3 to 33.3 μg/ml. They were more effective than pomegranate ethanolic seed extract with IC(50) ranging from 33.3 to 333 μg/ml. Antioxidant action of the novel compounds was documented in a DPPH test and in a liposomal membrane model, oxidatively stressed by peroxyl radicals. All the plant extracts showed considerable antioxidant potential in the DPPH assay. Pomegranate ethanolic hull extract and commercial pomegranate hull extract executed similar protective effects on peroxidatively damaged liposomal membranes characterized by 10ethanolic seed extract showed significantly lower antioxidant activity compared to both hull extracts studied. Pomegranate extracts are thus presented as bifunctional agents combining aldose reductase inhibitory action with antioxidant activity and with potential therapeutic use in prevention of diabetic complications.

  20. Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Guo, Chao; Zhu, Yanrong; Weng, Yan; Wang, Shiquan; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

    2014-01-01

    Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50mg/kg breviscapine at different time-points of reperfusion. After 24h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h of reperfusion. The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway

  1. Thymoquinone and its therapeutic potentials.

    Science.gov (United States)

    Darakhshan, Sara; Bidmeshki Pour, Ali; Hosseinzadeh Colagar, Abasalt; Sisakhtnezhad, Sajjad

    2015-01-01

    Herbal medicine has attracted great attention in the recent years and is increasingly used as alternatives to chemical drugs. Several lines of evidence support the positive impact of medicinal plants in the prevention and cure of a wide range of diseases. Thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa seeds and most properties of N sativa are mainly attributed to TQ. A number of pharmacological actions of TQ have been investigated including anti-oxidant, anti-inflammatory, immunomodulatory, anti-histaminic, anti-microbial and anti-tumor effects. It has also gastroprotective, hepatoprotective, nephroprotective and neuroprotective activities. In addition, positive effects of TQ in cardiovascular disorders, diabetes, reproductive disorders and respiratory ailments, as well as in the treatment of bone complications as well as fibrosis have been shown. In addition, a large body of data shows that TQ has very low adverse effects and no serious toxicity. More recently, a great deal of attention has been given to this dietary phytochemical with an increasing interest to investigate it in pre-clinical and clinical researches for assessing its health benefits. Here we report on and analyze numerous properties of the active ingredient of N. sativa seeds, TQ, in the context of its therapeutic potentials for a wide range of illnesses. We also summarize the drug's possible mechanisms of action. The evidence reported sugests that TQ should be developed as a novel drug in clinical trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Reconvene and reconnect the antioxidant hypothesis in human health and disease.

    Science.gov (United States)

    Singh, P P; Chandra, Anu; Mahdi, Farzana; Roy, Ajanta; Sharma, Praveen

    2010-07-01

    human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 μmol/l; 27.5-30 μmol/l; 40-50 μmol/l and 0.4-0.5 μmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overarching issues are (1) therapeutic value as adjuvant therapy in management of diseases (2) supplemental value in developing population (3) selective interactivity of antioxidant in different tissues and on different substrates (4) quantitative contribution in redox balance (5) mechanisms of adverse action on excess supplementation (6) advantages and disadvantages of prooxidant behavior of antioxidants (7) behavior in cohorts with polymorphic differences (8) interaction and intervention in radiotherapy, diabetes and diabetic complications and cardiovascular diseases (9) preventive behavior in neurological disorders (10) benefits of non-nutrient dietary antioxidants (11) markers to assess optimized antioxidants status (12) assessment of benefits of supplementation in alcoholics and heavy smokers. The unresolved and intriguing issues are (1) many compounds such as vitamin A and many others possessing both antioxidant and non-antioxidant

  3. Antioxidant Properties of Probiotic Bacteria.

    Science.gov (United States)

    Wang, Yang; Wu, Yanping; Wang, Yuanyuan; Xu, Han; Mei, Xiaoqiang; Yu, Dongyou; Wang, Yibing; Li, Weifen

    2017-05-19

    Oxidative stress defines a condition in which the prooxidant-antioxidant balance in the cell is disturbed, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells' viability. Probiotics have been known for many beneficial health effects, and the consumption of probiotics alone or in food shows that strain-specific probiotics can present antioxidant activity and reduce damages caused by oxidation. However, the oxidation-resistant ability of probiotics, especially the underling mechanisms, is not properly understood. In this view, there is interest to figure out the antioxidant property of probiotics and summarize the mode of action of probiotic bacteria in antioxidation. Therefore, in the present paper, the antioxidant mechanisms of probiotics have been reviewed in terms of their ability to improve the antioxidant system and their ability to decrease radical generation. Since in recent years, oxidative stress has been associated with an altered gut microbiota, the effects of probiotics on intestinal flora composition are also elaborated.

  4. Structural, Chemical and Biological Aspects of Antioxidants for Strategies Against Metal and Metalloid Exposure

    Directory of Open Access Journals (Sweden)

    Swaran J. S. Flora

    2009-01-01

    Full Text Available Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.

  5. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    A narrow therapeutic window. □ Good correlation between drug ... Antiretroviral therapeutic drug monitoring (TDM) is an additional monitoring tool to assist in the management of HIV-infected patients. Antiretroviral TDM is ... Antiretroviral TDM could play an important adjunctive role in our area. Clearly this will be a limited ...

  6. Antiglycation and Antioxidant Properties of Momordica charantia.

    Science.gov (United States)

    Aljohi, Ali; Matou-Nasri, Sabine; Ahmed, Nessar

    2016-01-01

    The accumulation of advanced glycation endproducts (AGEs) and oxidative stress underlie the pathogenesis of diabetic complications. In many developing countries, diabetes treatment is unaffordable, and plants such as bitter gourd (or bitter melon; Momordica charantia) are used as traditional remedies because they exhibit hypoglycaemic properties. This study compared the antiglycation and antioxidant properties of aqueous extracts of M. charantia pulp (MCP), flesh (MCF) and charantin in vitro. Lysozyme was mixed with methylglyoxal and 0-15 mg/ml of M. charantia extracts in a pH 7.4 buffer and incubated at 37°C for 3 days. Crosslinked AGEs were assessed using gel electrophoresis, and the carboxymethyllysine (CML) content was analyzed by enzyme-linked immunosorbent assays. The antioxidant activities of the extracts were evaluated using assays to assess DPPH (1,1-diphenyl-2-picryl-hydrazyl) and hydroxyl radical scavenging activities, metal-chelating activity and reducing power of the extracts. The phenolic, flavonol and flavonoid content of the extracts were also determined. All extracts inhibited the formation of crosslinked AGEs and CML in a dose-dependent manner, with MCF being the most potent. The antioxidant activity of MCF was higher than that of MCP, but MCP showed the highest metal-chelating activity. MCF had the highest phenolic and flavonoid contents, whereas MCP had the highest flavonol content. M. charantia has hypoglycaemic effects, but this study shows that M. charantia extracts are also capable of preventing AGE formation in vitro. This activity may be due to the antioxidant properties, particularly the total phenolic content of the extracts. Thus, the use of M. charantia deserves more attention, as it may not only reduce hyperglycaemia but also protect against the build-up of tissue AGEs and reduce oxidative stress in patients with diabetes.

  7. Antiglycation and Antioxidant Properties of Momordica charantia.

    Directory of Open Access Journals (Sweden)

    Ali Aljohi

    Full Text Available The accumulation of advanced glycation endproducts (AGEs and oxidative stress underlie the pathogenesis of diabetic complications. In many developing countries, diabetes treatment is unaffordable, and plants such as bitter gourd (or bitter melon; Momordica charantia are used as traditional remedies because they exhibit hypoglycaemic properties. This study compared the antiglycation and antioxidant properties of aqueous extracts of M. charantia pulp (MCP, flesh (MCF and charantin in vitro. Lysozyme was mixed with methylglyoxal and 0-15 mg/ml of M. charantia extracts in a pH 7.4 buffer and incubated at 37°C for 3 days. Crosslinked AGEs were assessed using gel electrophoresis, and the carboxymethyllysine (CML content was analyzed by enzyme-linked immunosorbent assays. The antioxidant activities of the extracts were evaluated using assays to assess DPPH (1,1-diphenyl-2-picryl-hydrazyl and hydroxyl radical scavenging activities, metal-chelating activity and reducing power of the extracts. The phenolic, flavonol and flavonoid content of the extracts were also determined. All extracts inhibited the formation of crosslinked AGEs and CML in a dose-dependent manner, with MCF being the most potent. The antioxidant activity of MCF was higher than that of MCP, but MCP showed the highest metal-chelating activity. MCF had the highest phenolic and flavonoid contents, whereas MCP had the highest flavonol content. M. charantia has hypoglycaemic effects, but this study shows that M. charantia extracts are also capable of preventing AGE formation in vitro. This activity may be due to the antioxidant properties, particularly the total phenolic content of the extracts. Thus, the use of M. charantia deserves more attention, as it may not only reduce hyperglycaemia but also protect against the build-up of tissue AGEs and reduce oxidative stress in patients with diabetes.

  8. Protective Role for Antioxidants in Acute Kidney Disease

    Directory of Open Access Journals (Sweden)

    Joanne M. Dennis

    2017-07-01

    Full Text Available Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI, induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C, is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status.

  9. Non-surgical care for locally advanced breast cancer: radiologically assessed therapeutic outcome of a new enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) with systemic chemotherapy.

    Science.gov (United States)

    Miyatake, Kana; Kubota, Kei; Ogawa, Yasuhiro; Hamada, Norihiko; Murata, Yoriko; Nishioka, Akihito

    2010-11-01

    We have previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which markedly enhances radiotherapeutic effects on various types of locally advanced malignant neoplasms. KORTUC II was approved by our local ethics committee for use against various types of malignant neoplasms. A maximum of 6 ml of radiosensitizer was injected into tumor tissue under ultrasonographic guidance just before each administration of radiotherapy. Seventeen patients with locally advanced breast cancer were enrolled to receive KORTUC II with systemic chemotherapy without surgical care. Patients were eligible if they had declined surgical treatment. Median observation period was 13.4 months (range, 1-26 months). This therapy was well tolerated. Contrast-enhanced magnetic resonance imaging revealed complete response in all primary breast tumors, and no patients displayed local recurrence during the follow-up period. Ultrasonography depicted tumor-like findings in 9 of 17 cases after therapy. The existence rate of posterior shadow artifacts behind the tumor was 2/17 before therapy, increasing to 8/17 after therapy. Intratumoral flow signals on color Doppler sonography were seen in 16/17 cases before therapy, but had disappeared from all cases after therapy. The increased rate of posterior shadow artifacts and absence of flow signals after therapy suggest that the tumor-like finding on ultrasonography represents scar tissue. Computed tomography revealed positive axillary nodes metastases in 16/17 and 2/17 cases before and after therapy, respectively. Nodal metastatic failure affected only 1 patient, who refused adjuvant systemic chemotherapy at the end of the observation period. Abnormal lymph node findings on computed tomography remained stable in the other patient. Excellent locoregional control based on accurate radiological evaluation implies that KORTUC II with chemotherapy has the

  10. Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes.

    Science.gov (United States)

    Han, Kyu-Ho; Hashimoto, Naoto; Fukushima, Michihiro

    2016-01-07

    Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

  11. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  12. Therapeutic vaccination for HPV induced cervical cancers.

    Science.gov (United States)

    Brinkman, Joeli A; Hughes, Sarah H; Stone, Pamela; Caffrey, Angela S; Muderspach, Laila I; Roman, Lynda D; Weber, Jeffrey S; Kast, W Martin

    2007-01-01

    Cervical Cancer is the second leading cause of cancer-related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  13. Redox Control of Leukemia: From Molecular Mechanisms to Therapeutic Opportunities

    Science.gov (United States)

    Irwin, Mary E.; Rivera-Del Valle, Nilsa

    2013-01-01

    Abstract Reactive oxygen species (ROS) play both positive and negative roles in the proliferation and survival of a cell. This dual nature has been exploited by leukemia cells to promote growth, survival, and genomic instability—some of the hallmarks of the cancer phenotype. In addition to altered ROS levels, many antioxidants are dysregulated in leukemia cells. Together, the production of ROS and the expression and activity of antioxidant enzymes make up the primary redox control of leukemia cells. By manipulating this system, leukemia cells gain proliferative and survival advantages, even in the face of therapeutic insults. Standard treatment options have improved leukemia patient survival rates in recent years, although relapse and the development of resistance are persistent challenges. Therapies targeting the redox environment show promise for these cases. This review highlights the molecular mechanisms that control the redox milieu of leukemia cells. In particular, ROS production by the mitochondrial electron transport chain, NADPH oxidase, xanthine oxidoreductase, and cytochrome P450 will be addressed. Expression and activation of antioxidant enzymes such as superoxide dismutase, catalase, heme oxygenase, glutathione, thioredoxin, and peroxiredoxin are perturbed in leukemia cells, and the functional consequences of these molecular alterations will be described. Lastly, we delve into how these pathways can be potentially exploited therapeutically to improve treatment regimens and promote better outcomes for leukemia patients. Antioxid. Redox Signal. 18, 1349–1383. PMID:22900756

  14. Yucca: A medicinally significant genus with manifold therapeutic attributes

    OpenAIRE

    Patel, Seema

    2012-01-01

    The genus Yucca comprising of several species is dominant across the chaparrals, canyons and deserts of American South West and Mexico. This genus has long been a source of sustenance and drugs for the Native Americans. In the wake of revived interest in drug discovery from plant sources, this genus has been investigated and startling nutritive and therapeutic capacities have come forth. Apart from the functional food potential, antioxidant, antiinflammation, antiarthritic, anticancer, antidi...

  15. Impact of Antioxidants on Cardiolipin Oxidation in Liposomes: Why Mitochondrial Cardiolipin Serves as an Apoptotic Signal?

    Science.gov (United States)

    Lokhmatikov, Alexey V; Voskoboynikova, Natalia; Cherepanov, Dmitry A; Skulachev, Maxim V; Steinhoff, Heinz-Jürgen; Skulachev, Vladimir P; Mulkidjanian, Armen Y

    2016-01-01

    Molecules of mitochondrial cardiolipin (CL) get selectively oxidized upon oxidative stress, which triggers the intrinsic apoptotic pathway. In a chemical model most closely resembling the mitochondrial membrane-liposomes of pure bovine heart CL-we compared ubiquinol-10, ubiquinol-6, and alpha-tocopherol, the most widespread naturally occurring antioxidants, with man-made, quinol-based amphiphilic antioxidants. Lipid peroxidation was induced by addition of an azo initiator in the absence and presence of diverse antioxidants, respectively. The kinetics of CL oxidation was monitored via formation of conjugated dienes at 234 nm. We found that natural ubiquinols and ubiquinol-based amphiphilic antioxidants were equally efficient in protecting CL liposomes from peroxidation; the chromanol-based antioxidants, including alpha-tocopherol, were 2-3 times less efficient. Amphiphilic antioxidants, but not natural ubiquinols and alpha-tocopherol, were able, additionally, to protect the CL bilayer from oxidation by acting from the water phase. We suggest that the previously reported therapeutic efficiency of mitochondrially targeted amphiphilic antioxidants is owing to their ability to protect those CL molecules that are inaccessible to natural hydrophobic antioxidants, being trapped within respiratory supercomplexes. The high susceptibility of such occluded CL molecules to oxidation may have prompted their recruitment as apoptotic signaling molecules by nature.

  16. The role of the antioxidant system during intense endurance exercise: lessons from migrating birds.

    Science.gov (United States)

    Cooper-Mullin, Clara; McWilliams, Scott R

    2016-12-01

    During migration, birds substantially increase their metabolic rate and burn fats as fuel and yet somehow avoid succumbing to overwhelming oxidative damage. The physiological means by which vertebrates such as migrating birds can counteract an increased production of reactive species (RS) are rather limited: they can upregulate their endogenous antioxidant system and/or consume dietary antioxidants (prophylactically or therapeutically). Thus, birds can alter different components of their antioxidant system to respond to the demands of long-duration flights, but much remains to be discovered about the complexities of RS production and antioxidant protection throughout migration. Here, we use bird migration as an example to discuss how RS are produced during endurance exercise and how the complex antioxidant system can protect against cellular damage caused by RS. Understanding how a bird's antioxidant system responds during migration can lend insights into how antioxidants protect birds during other life-history stages when metabolic rate may be high, and how antioxidants protect other vertebrates from oxidative damage during endurance exercise. © 2016. Published by The Company of Biologists Ltd.

  17. Protective effect of different antioxidant agents in UVB-irradiated keratinocytes

    Directory of Open Access Journals (Sweden)

    Sara Salucci

    2017-09-01

    Full Text Available Skin cells can respond to UVB-induced damage either by tolerating it, or restoring it through antioxidant activation and DNA repair mechanisms or, ultimately, undergoing programmed cell death, when damage is massive. Nutritional factors, in particular, food antioxidants, have attracted much interest because of their potential use in new preventive, protective, and therapeutic strategies for chronic degenerative diseases, including skin inflammation and cancer. Some polyphenols, present in virgin olive oil, well tolerated by organism after oral administration, show a variety of pharmacological and clinical benefits such as anti-oxidant, anti-cancer, anti-inflammatory, and neuro-protective activities. Here, the protective effects of antioxidant compounds against UV-induced apoptosis have been described in HaCat cell line. Human keratinocytes were pre-treated with antioxidants before UVB exposure and their effects have been evaluated by means of ultrastructural analyses. After UVB radiation, a known cell death trigger, typical apoptotic features, absent in control condition and in antioxidant alone-treated cells, appear. An evident numerical decrease of ultrastructural apoptotic patterns and TUNEL positive nuclei can be observed when natural antioxidants were supplied before cell death induction. These data have been confirmed by molecular investigation of caspase activity. In conclusion, this paper highlights antioxidant compound ability to prevent apoptotic cell death in human keratinocytes exposed to UVB, suggesting, for these molecules, a potential role in preventing skin damage. 

  18. Antioxidant relevance to human health.

    Science.gov (United States)

    Wahlqvist, Mark L

    2013-01-01

    Human ecology requires both oxygen and water with the generation from food of an immediate energy source, ATP, by oxidative phosphorylation. A continuing balance between oxidation and antioxidation is necessary for longer less-disabled lives, taking account of oxidative stresses and the critical roles of oxidants in defence against infection, tissue repair and signalling. Antioxidant capacity is derived both exogenously (from food, beverage and sunlight) and endogenously (from enzymatic and non-enzymatic pathways). A number of oxidant food factors service antioxidant metallo-enzymes. The capacity operates extra- or intracellularly. Uric acid is the major antioxidant in primate blood. Uric acid synthesis is increased by dietary fructose from fruit, sugary foods and drinks. This indirect antioxidant effect of fruit is separate from that attributable to its flavonoids. Alcohol also increases serum uric acid. Urate excess and retention is associated with disease. The high prevalence of hyperuricaemia in NE Asia presents a major public health dilemma in regard to putative benefits and risks. Foods with high antioxidant activity include berries, nuts and legumes, tomatoes and sweet potato leaves. Each of the antioxidants in these foods is pleiotropic being inter-alia anti-inflammatory, anti-angiogenic or anti-neoplastic. Moreover, food matrices and patterns contribute to the safety of antioxidant consumption. There is no evidence to date that isolated antioxidants as food supplements improve health outcomes or survival; and some that indicate unacceptable risk. Their use as biomarkers of food cannot justify their isolated use. Nevertheless, a spectrum of dietary pluripotential antioxidants for tissues, metabolic and immune systems is advantageous.

  19. Levodopa: History and Therapeutic Applications.

    Science.gov (United States)

    Ovallath, Sujith; Sulthana, Bahiya

    2017-01-01

    Levodopa - the aromatic amino acid L-3,4-dihydroxy phenylalanine has held the attention of neurologists and pharmacologists alike for more than half a century. Even though extensive research has been done across the globe in treatment of Parkinson's disease, with different molecules, none could replace the gold standard treatment or provide complete relief for the debilitated. Although research brought us better tips and tricks to modulate the dopamine blood levels to balance between the desired and deleterious effects, it could never replace the basic substrate. From simple oral preparation to more advanced treatment like duodenal dopa administration for better efficacy and compliance, L-dopa has sure undergone scrutiny and stayed strong as the fundamental neurotransmitter replacement therapy to pave path for many more new therapeutic strategies. So as a token of gratitude to the revolutionary agent and pioneers behind it, a trip down the memory lane is in order.

  20. Host modulation by therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2012-01-01

    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  1. Guidelines for Rational Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  2. [Therapeutic update in cystic fibrosis].

    Science.gov (United States)

    Durupt, S; Nove Josserand, R; Durieu, I

    2014-06-01

    We present the recent therapeutic advances in the cystic fibrosis care. It concerns improvements in symptomatic treatment with the development of dry powder inhaled antibiotics that improved quality of life, and innovative treatments namely the modulators of the cystic fibrosis transmembrane protein conductance regulator (CFTR), molecules which act specifically at the level of the defective mechanisms implied in the disease. The life expectancy of cystic fibrosis patients born after 2000, is estimated now to be about 50 years. This improvement of survival was obtained with the organization of the care within the specialized centers for cystic fibrosis (Centre de ressource et de compétences de la mucoviscidose) and remains still based on heavy symptomatic treatments. Dry powder inhaled antibiotics constitute a significant time saving for patients to whom all the care can achieve two hours daily. Since 2012, the modulators of CFTR, molecules allowing a pharmacological approach targeted according to the type of the mutations, allows a more specific approach of the disease. Ivacaftor (Kalydeco(®)) which potentialises the function of the CFTR protein expressed on the cellular surface is now available for patients with the G551D mutation. Lumacaftor is going to be tested in association with ivacaftor in patients with the F508del mutation, that is present in at least 75% of the patients. The ataluren which allows the production of a functional protein CFTR in patients with a no sense mutation is the third representing of this new therapeutic class. We presently have numerous symptomatic treatments for the cystic fibrosis care. The development of CFTR modulators, today available to a restricted number of patients treated with ivacaftor represents a very promising therapeutic avenue. It will represent probably the first step to a personalized treatment according to CFTR genotype. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by

  3. Pre-therapeutic dosimetry and biodistribution of {sup 86}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide versus {sup 111}In-pentetreotide in patients with advanced neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Helisch, Andreas; Foerster, Gregor J.; Reber, Helmut; Buchholz, Hans-Georg; Bartenstein, Peter [University of Mainz, Department of Nuclear Medicine, Mainz (Germany); Arnold, Rudolf [Philips University, Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Marburg (Germany); Goeke, Burkhard [Ludwig-Maximilians-University, Department of Internal Medicine II, Klinikum Grosshadern, Munich (Germany); Weber, Matthias M. [University of Mainz, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mainz (Germany); Wiedenmann, Bertram [Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Charite Medical School, Berlin (Germany); Pauwels, Stanislas [Catholic University of Louvain, Center of Nuclear Medicine, Brussels (Belgium); Haus, Ulrike [Novartis Pharmaceuticals, Nuremberg (Germany); Bouterfa, Hakim [Novartis Pharmaceuticals, Basel (Switzerland)

    2004-10-01

    For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with {sup 90}Y is frequently used [{sup 90}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical {sup 86}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide (considered as the gold standard) and the commercially available {sup 111}In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq {sup 90}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with {sup 90}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq {sup 90}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 ({sup 86}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 ({sup 111}In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with {sup 86}Y-DOTA-Phe{sup 1}-Tyr{sup 3}-octreotide, dosimetry with {sup 111}In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy. (orig.)

  4. Complexity in the therapeutic delivery of RNAi medicines

    DEFF Research Database (Denmark)

    Colombo, Stefano; Zeng, Xianghui; Ragelle, Héloïse

    2014-01-01

    INTRODUCTION: Nucleic acids have witnessed a dramatic acceleration in their therapeutic exploitation and currently represent a growing number of applications in drug development pipelines. However, a more wide-spread development of therapeutics based on nucleic acids is restricted by their poor...... chemical and enzymatic stability in vivo, lack of cellular uptake and insufficient capability to reach intracellular targets. AREAS COVERED: Advanced formulation of nucleic acids in nano-sized carriers may help unlocking their potential as therapeutic agents. Nano-sized matters own specific features...... of this review is to reflect on the complexity in the therapeutic delivery of RNA interference-based drugs emerging from the recent clinical experiences and report the actual technological and analytical advances introduced to solve it. EXPERT OPINION: The complexity in the therapeutic delivery of nucleic acids...

  5. Antioxidant degradation kinetics in apples.

    Science.gov (United States)

    Arora, Bindvi; Sethi, Shruti; Joshi, Alka; Sagar, V R; Sharma, R R

    2018-04-01

    The effect of shelf storage under ambient conditions of cut apple dices on degradation of bioactive compounds such ascorbic acid, total phenols, antioxidant activity (% DPPH inhibition) and PPO activity were investigated. The results indicated that antioxidant activity declined significantly over 80 min storage of diced apples at ambient temperature. Similar trend was observed for ascorbic acid, total phenols and PPO activity. Ascorbic acid, total phenols and antioxidant activity degradation followed first-order kinetics where the rate constant (k) was found to be in range for all the thirteen cultivars, though initial ascorbic acid and phenol content varied in different apple cultivars. The reaction rate constant (k) for first order degradation ranged from 1.16 to 1.97, 0.89 to 1.29 and 0.37 to 1.54 for antioxidant activity, total phenols and ascorbic acid, respectively. This explains that antioxidant activity degrades at higher rate than total phenols and ascorbic acid, which also corroborates that antioxidant activity is affected by both total phenols and ascorbic acid content. In general, total antioxidant activity for apple dices kept for 80 min under ambient conditions exhibited lower values as compared to control.

  6. Antioxidant, antiglycation and cytotoxicity evaluation of selected medicinal plants of the Mascarene Islands

    Directory of Open Access Journals (Sweden)

    Mahomoodally Fawzi M

    2012-09-01

    Full Text Available Abstract Background Many indigenous plants of Mascarene Islands have been used in folkloric medicine to manage diabetes but few species have received scientific attention. Selected traditional medicinal plants (Antidesma madagascariense Lam. -Euphorbiaceae (AM, Erythroxylum macrocarpum O.E.Schulz -Erythroxylaceae (EM, Pittosporum senacia Putterl -Pittosporaceae (PS, Faujasiopsis flexuosa Lam. C.Jeffrey -Asteraceae (FF, Momordica charantia Linn -Cucurbitaceae (MC and Ocimum tenuiflorum L -Lamiaceae (OT were evaluated for their antioxidant, antiglycation and cytotoxic potential in vitro. Methods Graded concentrations (1.25-100 μg/mL of the crude methanolic and water extracts and fractions (dichloromethane, ethyl-acetate, n-butanol and water were evaluated for abilities to scavenge 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH, nitric oxide (NO, superoxide (SO radicals and to inhibit lipoxygenase and formation of advanced glycation endproduct (AGE in vitro. The MTT (3-(4, 5-dimethylthazol-2-yl-2,5-diphenyl tetrazonium bromide cytotoxicity test was performed on 3T3 cell line. Results Only IC50 for DPPH, SO, NO and lipoxygenase for AM, FF and OT crude extracts and fractions were comparable to ascorbic acid and quercetin activity. Crude aqueous extracts of AM and FF showed IC50 of 4.08 and 3.89 μg/mL respectively for lipoxygenase which was significantly lower (p n-butanol fractions also showed antiglycation activities (p Conclusion AM, FF and OT crude extracts and fractions have potent antioxidant and antiglycation properties with no apparent cytotoxicity and might have prophylactic and therapeutic potentials in the management of diabetes and related complications. Our study tends to validate the traditional use of these medicinal herbs and food plants as complementary and alternative medicines.

  7. Molecular Engineering Solutions for Therapeutic Peptide Delivery.

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan; Ting, Jeffrey M.; Srivastava, Samanvaya; LaBelle, James L.; Tirrell, Matthew V.

    2017-11-07

    Proteins and their interactions in and out of cells must be well-orchestrated for the healthy functioning and regulation of the body. Even the slightest disharmony can cause diseases. Therapeutic peptides are short amino acid sequences (generally considered <50 amino acids) that can naturally mimic the binding interfaces between proteins and thus, influence protein-protein interactions. Because of their fidelity of binding, peptides are a promising next generation of personalized medicines to reinstate biological harmony. Peptides as a group are highly selective, relatively safe, and biocompatible. However, they are also vulnerable to many in vivo pharmacologic barriers limiting their clinical translation. Current advances in molecular, chemical, and nanoparticle engineering are helping to overcome these previously insurmountable obstacles and improve the future of peptides as active and highly selective therapeutics. In this review, we focus on self-assembled vehicles as nanoparticles to carry and protect therapeutic peptides through this journey, and deliver them to the desired tissue.

  8. Nanotechnology—novel therapeutics for CNS disorders

    Science.gov (United States)

    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

  9. Relationships between Age, Daily Physical Activity, Antioxidant Capacity and Oxidative Stress among Middle-aged and Elderly People

    OpenAIRE

    Tanabe, Kai; Masuda, Kazumi; Ajisaka, Ryuichi; Matsuda, Mitsuo; Hirayama, Aki; Nagase, Shoji; Kono, Ichiro; Kuno, Shinya

    2006-01-01

    The effects of age and daily physical activity (PA) on antioxidant capacity and oxidative stress remains unclear, especially among advanced age population. Thus the present study evaluated antioxidant capacity and oxidative stress status, taking into account age and PA in healthy middle-aged and elderly people (45-92 years, n=436; 166 males and 270 females). The advanced age subjects were classified in groups according to their age. Data collected from young male subjects (18-26 years, n=36) ...

  10. Innovative therapeutics for inflammatory bowel disease

    OpenAIRE

    Yamamoto-Furusho, Jesus K

    2007-01-01

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn’s disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different le...

  11. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...... garnered a great deal of interest due to the substantial room for improvement inherent to conventional chemotherapeutic agents. Chemotherapeutic agents and antiviral agents have a lot of features in common due to both of them typically targeting endogenous targets, unlike antibacterial compounds, though...... the examples of polymer therapeutics being applied as an antiviral treatment are few and far in-between. This work aims to explore antiviral therapeutics, specifically in context of hepatitis virus C (HCV) and HIV. The current treatment of hepatitis C consists of a combination of drugs, of which ribavirin...

  12. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  13. Genesis and development of DPPH method of antioxidant assay

    OpenAIRE

    Kedare, Sagar B.; Singh, R. P.

    2011-01-01

    α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging method offers the first approach for evaluating the antioxidant potential of a compound, an extract or other biological sources. This is the simplest method, wherein the prospective compound or extract is mixed with DPPH solution and absorbance is recorded after a defined period. However, with the advancement and sophistication in instrumental techniques, the method has undergone various modifications to suit the requirements, even...

  14. Oxidative stress impairs the haemodynamic activity of cardiovascular agents with antioxidant properties

    NARCIS (Netherlands)

    Sand, C.; Peters, S. L.; Pfaffendorf, M.; van Zwieten, P. A.

    2001-01-01

    Reactive oxygen species (ROS) are known to be involved in the pathogenesis and progression of various cardiovascular diseases. For some therapeutics like carvedilol and captopril used in the treatment of such diseases antioxidant properties have been proposed to play a role in addition to their

  15. Biological activities (anti-inflammatory and anti-oxidant) of fractions ...

    African Journals Online (AJOL)

    Background: Bryophytes like other lower plants (non-vascular plants) are not traditionally employed for therapeutic purposes. Hence this study evaluated the in vitro anti-oxidant potentials and anti-inflammatory activities of the fractions and methanolic extract of Moss (Philonotis hastata, Duby) with a view to studying its ...

  16. Antioxidative activity of high-density lipoprotein (HDL: Mechanistic insights into potential clinical benefit

    Directory of Open Access Journals (Sweden)

    Fernando Brites

    2017-12-01

    Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target.

  17. Therapeutic neutrality reconsidered.

    Science.gov (United States)

    Humphries, R H

    1982-06-01

    This paper suggests that therapists' tendency to ignore the impact of their own religious beliefs on their patients constitutes an area of potential abuse of psychotherapy. The author reviews the religious stance of the founders of psychotherapy, as well as recent criticisms of the therapeutic process, and proposes steps to safeguard against the inadvertent fostering of therapists' religious views on the patient.

  18. Development of Antibody Therapeutics against Flaviviruses

    Science.gov (United States)

    Sun, Haiyan; Chen, Qiang; Lai, Huafang

    2017-01-01

    Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates. PMID:29295568

  19. THE EFFECTS OF NICOTINE TREATMENT ON THE ANTIOXIDANT ENZIMES ACTIVITY IN THE RAT BRAIN

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-12-01

    Full Text Available Nicotine has been reported to be therapeutic in some patients with certain neurodegenerative diseases and to have neuroprotective effects in the central nervous system. However, nicotine administration may result in oxidative stress by inducing the generation of reactive oxygen species in the periphery and central nervous system. There is also evidence suggesting that nicotine may have antioxidant properties in the central nervous system. The antioxidant properties of nicotine may be intracellular through the activation of the nicotinic receptors or extracellular by acting as a radical scavenger in that it binds to iron. The possibility that nicotine might be used to treat some symptoms of certain neurodegenerative diseases underlies the necessity to determine whether nicotine has pro-oxidant, antioxidant or properties of both. In the present study we evaluated the effects of nicotine treatment (0.3 mg/kg g.c., i.p., SIGMA, 7 continuous days administration, on the antioxidant enzymes activity.

  20. Structural characterization and antioxidant activities of polysaccharides from Citrus aurantium L.

    Science.gov (United States)

    Wang, Qiu Hong; Shu, Zun Peng; Xu, Bing Qing; Xing, Na; Jiao, Wen Juan; Yang, Bing You; Kuang, Hai Xue

    2014-06-01

    Three polysaccharide fractions were obtained from Citrus aurantium L. (CAL) by sequential extraction with cold water, hot water, and 1.0M NaOH, respectively. The fractions were denoted CALA, CALB, and CALC. Structural characterization was conducted by physicochemical property, FTIR, and SEM analyses. Antioxidant activities in vivo and in vitro were also evaluated. CALB, which showed the highest activity, was further isolated to afford four purified polysaccharides (CALB-1-4) by various ion exchange and gel-filtration chromatography. Meanwhile, the purified polysaccharides were subjected to composition analysis and screened by antioxidant activity in vitro. Among the four purified polysaccharides, CALB-3 had the highest antioxidant activity and its structure was analyzed by FTIR, SEM and AFM microscopy. Overall, these results indicated that polysaccharides from CAL had potential therapeutic applications in the medical and food industries because of their antioxidant activities. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Haifeng Li

    2017-07-01

    Full Text Available Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities.

  2. Glutathione: new roles in redox signalling for an old antioxidant

    Directory of Open Access Journals (Sweden)

    KATIA eAQUILANO

    2014-08-01

    Full Text Available The physiological roles played by the tripeptide glutathione have greatly advanced over the past decades superimposing the research on free radicals, oxidative stress and, more recently, redox signalling. In particular, GSH is involved in nutrient metabolism, antioxidant defence and regulation of cellular metabolic functions ranging from gene expression, DNA and protein synthesis to signal transduction, cell proliferation and apoptosis. This review will be focused on the role of GSH in cell signalling by analysing the more recent advancements about its capability to modulate nitroxidative stress, autophagy and viral infection.

  3. Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties.

    Science.gov (United States)

    Scipioni, Matteo; Kay, Graeme; Megson, Ian; Kong Thoo Lin, Paul

    2018-01-01

    Antioxidants have been the subject of intense research interest mainly due to their beneficial properties associated with human health and wellbeing. Phenolic molecules, such as naturally occurring Resveratrol and Vanillin, are well known for their anti-oxidant properties, providing a starting point for the development of new antioxidants. Here we report, for the first time, the synthesis of a number of new vanillin through the reductive amination reaction between vanillin and a selection of amines. All the compounds synthesised, exhibited strong antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c being the most active. The latter also demonstrated the ability to protect plasmid DNA from oxidative damage in the presence of the radical initiator AAPH. At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative damage (H 2 O 2 , 400 μM) with both 1b and 2c. The presence of a tertiary amino group, along with the number of vanillin moieties in the molecule contribute for the antioxidant activity. Furthermore, the delocalization of the electron pair of the nitrogen and the presence of an electron donating substituent to enhance the antioxidant properties of this new class of compounds. In our opinion, vanillin derivatives 1b and 2c described in this work can provide a viable platform for the development of antioxidant based therapeutics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Evaluation of antioxidant activity of Manihot esculenta Crantz in wistar rats.

    Science.gov (United States)

    Bahekar, Satish Eknath; Kale, Ranjana Sushil

    2016-01-01

    The study aimed to explore the antioxidant activity of ethanolic leaf extract of Manihot esculenta Crantz leaves (MEC) in wistar rats. Ethanolic extract of MEC leaves in the doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg were used in wistar rats of either sex. The oxidative stress was produced by overdose of acetaminophen and estimation of serum concentration of various enzymes such as malonaldehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) were measured by standard biochemical methods. Silymarin (100 mg/kg) was used as a standard drug for assessment of antioxidant status. Results were analyzed by one-way analysis of variance followed by Student's unpaired t-test. When compared with the standard antioxidant silymarin, MEC extract did not exhibit antioxidant activity in terms of MDA level reduction. However, it significantly increased serum levels of the antioxidant enzymes (SOD, GSH, and CAT) exerting a potent antioxidant effect in a graded manner. The observed results suggest that MEC could be a potential source of antioxidants. However, further studies are required to explore this therapeutic property of plant.

  5. Antioxidant and antidiabetic properties of tartary buckwheat rice flavonoids after in vitro digestion.

    Science.gov (United States)

    Bao, Tao; Wang, Ye; Li, Yu-Ting; Gowd, Vemana; Niu, Xin-He; Yang, Hai-Ying; Chen, Li-Shui; Chen, Wei; Sun, Chong-de

    Oxidative stress and diabetes have a tendency to alter protein, lipid, and DNA moieties. One of the strategic methods used to reduce diabetes-associated oxidative stress is to inhibit the carbohydrate-digesting enzymes, thereby decreasing gastrointestinal glucose production. Plant-derived natural antioxidant molecules are considered a therapeutic tool in the treatment of oxidative stress and diabetes. The objective of this study was to identify tartary buckwheat rice flavonoids and evaluate the effect of in vitro digestion on their antioxidant and antidiabetic properties. High performance liquid chromatography (HPLC) analysis indicated the presence of rutin as a major component and quercitrin as a minor component of both digested and non-digested flavonoids. Both extracts showed a significant antioxidant capacity, but digested flavonoids showed reduced activity compared to non-digested. There were some decreases of the antioxidant activities (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picrylhydrazy (DPPH) radical, and ferric reducing antioxidant power (FRAP)) of digested tartary buckwheat rice flavonoids compared with non-digested. Flavonoids from both groups significantly inhibited reactive oxygen species (ROS) production and α-glucosidase activity. Both digested and non-digested flavonoids markedly increased glucose consumption and glycogen content in HepG2 cells. Tartary buckwheat rice flavonoids showed appreciable antioxidant and antidiabetic properties, even after digestion. Tartary buckwheat rice appears to be a promising functional food with potent antioxidant and antidiabetic properties.

  6. Antioxidant gap and lipid peroxidation in patients with rheumatoid arthritis: Relationship to disease manifestations and activity

    Directory of Open Access Journals (Sweden)

    Anuradha B. Patil

    2012-10-01

    Full Text Available Objective: To explore relationships between total antioxidant gap and lipid peroxidation with respect to the disease severity of Rheumatoid arthritis (RA, which may have further implications in understanding rheumatoid pathology and therapeutic management of the disease. Method: The present of study was designed to investigate the relationship between antioxidant gap and certain antioxidant parameters with disease activity in rheumatoid arthritis patients. A significantly increased lipid peroxidation, measured as malondialdehyde (MDA, was demonstrated in the plasma of rheumatoid arthritis patients. Results: MDA was observed in RA patients (0.98暲0.34 毺 mol/L than those found in controls (0.98暲0.34 毺 mol/L. The antioxidant gap was significantly decreased. total antioxidant gap (0.34暲0.14 mmol/L and total antioxidant capacity (1.34 暲0.16 mmol/L were significantly lower in RA patients as compared to healthy controls (0.76暲0.33 and 1.78暲0.35 mmol/Lrespectivel. Discussion: The excessive production of ROS disturbs redox status including antioxidant gap and can exacerbating inflammation and affecting tissue damage in RA, as exemplified by their strong association with disease activity

  7. Antioxidants stabilizing fish oils : effect of antioxidant, storage temperature and type of fish oil

    OpenAIRE

    Kasbo, Mari Kristine

    2012-01-01

    The aim of this study was to investigate four commercially available antioxidants in two fish oils. The antioxidants were investigated to see which one of them is most efficient in preventing oxidation. Antioxidants were added in three levels to find the optimal concentration. In addition a possible synergistic effect between the antioxidants was investigated. Two different oils with different concentration of EPA and DHA were added antioxidants. Four of the antioxidants were single antioxida...

  8. Chemical Profiling and Evaluation of Antioxidant and Anti-Microbial Properties of Selected Commercial Essential Oils: A Comparative Study

    OpenAIRE

    Lu?s, ?ngelo; Duarte, Ana Paula; Pereira, Lu?sa; Domingues, Fernanda

    2017-01-01

    Background: The last decades have seen an increased awareness by the scientific community of the extent of resistance to conventional antibiotics, particularly with respect to the emerging multidrug-resistant pathogenic microbes. Additionally, natural antioxidants have received significant attention among food professionals and consumers because of their assumed safety and potential therapeutic value. The aim of this work was to assess the antioxidant activities of eight selected commercial e...

  9. Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review.

    Science.gov (United States)

    Venardos, Kylie M; Perkins, Anthony; Headrick, John; Kaye, David M

    2007-01-01

    Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as superoxide dismutase, catalase, and the glutathione peroxidase and thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve

  10. Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet.

    Science.gov (United States)

    Pérez-Jiménez, Jara; Díaz-Rubio, M Elena; Saura-Calixto, Fulgencio

    2015-12-01

    Epidemiological and clinical studies show that diets with a high antioxidant capacity, such us those rich in plant food and beverages, are associated with significant decreases in the overall risk of cardiovascular disease or colorectal cancer. Current studies on dietary antioxidants and dietary antioxidant capacity focus exclusively on low molecular weight or soluble antioxidants (vitamins C and E, phenolic compounds and carotenoids), ignoring macromolecular antioxidants. These are polymeric phenolic compounds or polyphenols and carotenoids linked to plant food macromolecules that yield bioavailable metabolites by the action of the microbiota with significant effects either local and/or systemic after absorption. This study determined the antioxidant capacity of the Spanish Mediterranean diet including for the first time both soluble and macromolecular antioxidants. Antioxidant capacity and consumption data of the 54 most consumed plant foods and beverages were used. Results showed that macromolecular antioxidants are the major dietary antioxidants, contributing a 61% to the diet antioxidant capacity (8000 μmol Trolox, determined by ABTS method). The antioxidant capacity data for foods and beverages provided here may be used to estimate the dietary antioxidant capacity in different populations, where similar contributions of macromolecular antioxidants may be expected, and also to design antioxidant-rich diets. Including macromolecular antioxidants in mechanistic, intervention and observational studies on dietary antioxidants may contribute to a better understanding of the role of antioxidants in nutrition and health.

  11. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities.

    Science.gov (United States)

    Rodrigo, Ramón; Fernández-Gajardo, Rodrigo; Gutiérrez, Rodrigo; Matamala, José Manuel; Carrasco, Rodrigo; Miranda-Merchak, Andrés; Feuerhake, Walter

    2013-08-01

    Stroke is the second leading cause of death, after ischemic heart disease, and accounts for 9% of deaths worldwide. According to the World Health Organization [WHO], 15 million people suffer stroke worldwide each year. Of these, more than 6 million die and another 5 million are permanently disabled. Reactive oxygen species [ROS] have been implicated in brain injury after ischemic stroke. There is evidence that a rapid increase in the production of ROS immediately after acute ischemic stroke rapidly overwhelm antioxidant defences, causing further tissue damage. These ROS can damage cellular macromolecules leading to autophagy, apoptosis, and necrosis. Moreover, the rapid restoration of blood flow increases the level of tissue oxygenation and accountsfor a second burst of ROS generation, which leads to reperfusion injury. Current measures to protect the brain against severe stroke damage are insufficient. Thus, it is critical to investigate antioxidant strategies that lead to the diminution of oxidative injury. The antioxidant vitamins C and E, the polyphenol resveratrol, the xanthine oxidase [XO] inhibitor allopurinol, and other antioxidant strategies have been reviewed in the setting of strokes. This review focuses on the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of ischemic stroke, and the novel therapeutic strategies to be tested to reduce the cerebral damage related to both ischemia and reperfusion.

  12. Advanced Ceramics

    International Nuclear Information System (INIS)

    1989-01-01

    The First Florida-Brazil Seminar on Materials and the Second State Meeting about new materials in Rio de Janeiro State show the specific technical contribution in advanced ceramic sector. The others main topics discussed for the development of the country are the advanced ceramic programs the market, the national technic-scientific capacitation, the advanced ceramic patents, etc. (C.G.C.) [pt

  13. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity – Exploring the armoury of obscurity

    Directory of Open Access Journals (Sweden)

    Kanchanlata Singh

    2018-02-01

    The effect of supplementation of thirteen different antioxidants and their analogues as a single agent or in combination with chemotherapy has been compiled in this article. The present review encompasses a total of 174 peer-reviewed original articles from 1967 till date comprising 93 clinical trials with a cumulative number of 18,208 patients, 56 animal studies and 35 in vitro studies. Our comprehensive data suggests that antioxidant has superior potential of ameliorating chemotherapeutic induced toxicity. Antioxidant supplementation during chemotherapy also promises higher therapeutic efficiency and increased survival times in patients.

  14. Clinical and Therapeutic Trials of Nigella Sativa

    Directory of Open Access Journals (Sweden)

    Ragaa H.M. Salama

    2010-10-01

    Full Text Available Seeds of Nigella sativa (N. sativa have been used for thousands of years as a spice and food preservative. The oil and seed constituents have shown potential medicinal properties in traditional medicine. This review lists and discusses different therapeutic trials of N. sativa seeds and its active ingredients in many diseases affecting body systems. It has anti–oxidant effects through enhancing the oxidant scavenger system that leads to antitoxic effects induced by several insults. Its anti–inflammatory effects conduct through suppression of the inflammatory mediators’ prostaglandins and leukotriens. Its immunomodulatory properties were proved by augmenting the T cell and natural killer cell–mediated immune responses. It expresses antimicrobial and anti–tumor properties toward different microbes and cancers. It decreases DNA damage and thereby prevents initiation of carcinogenesis in colonic tissue secondary to exposure to toxic agents. N. sativa is of immense therapeutic benefit in DM. It stimulates glucose–induced secretion of insulin besides having a negative impact on glucose absorption from the intestinal mucosa. N. sativa administration protects hepatic tissue from deleterious effects of toxic substances and attenuates hepatic lipid peroxidation. N. sativa provides a promising strategy that combines anti–inflammatory, antioxidants, and antineoplastics modes of action. [TAF Prev Med Bull 2010; 9(5.000: 513-522

  15. Therapeutic potential of curcumin in digestive diseases.

    Science.gov (United States)

    Dulbecco, Pietro; Savarino, Vincenzo

    2013-12-28

    Curcumin is a low-molecular-weight hydrophobic polyphenol that is extracted from turmeric, which possesses a wide range of biological properties including anti-inflammatory, anti-oxidant, anti-proliferative and anti-microbial activities. Despite its diverse targets and substantial safety, clinical applications of this molecule for digestive disorders have been largely limited to case series or small clinical trials. The poor bioavailability of curcumin is likely the major hurdle for its more widespread use in humans. However, complexation of curcumin into phytosomes has recently helped to bypass this problem, as it has been demonstrated that this new lecithin formulation enables increased absorption to a level 29-fold higher than that of traditional curcuminoid products. This allows us to achieve much greater tissue substance delivery using significantly lower doses of curcumin than have been used in past clinical studies. As curcumin has already been shown to provide good therapeutic results in some small studies of both inflammatory and neoplastic bowel disorders, it is reasonable to anticipate an even greater efficacy with the advent of this new technology, which remarkably improves its bioavailability. These features are very promising and may represent a novel and effective therapeutic approach to both functional and organic digestive diseases.

  16. ANTIOXIDANT POTENCY OF WATER KEFIR

    Directory of Open Access Journals (Sweden)

    Muneer Alsayadi M.S.

    2013-06-01

    Full Text Available Reactive oxygen species (ROS have strong relationship with several diseases. Many fermented foods were reported to be important sources for antioxidant compounds. Antioxidant activity of water kefir never reported in the scientific literature. The objective of this study was to detect and investigate the antioxidant potency of water kefir. Water kefir was prepared by fermentation of sugar solution with kefir grains for 24h. Antioxidant activity of fresh water kefir drink and its extract with (0.125–5 mg/ml was evaluated using 2,2,-diphenyl-1-pricrylhydrozyl (DPPH scavenging method, and inhibition of ascorbate autoxidation and the reducing power of water kefir were determined, Butylated hydroxyanisole (BHA and ascorbic acid were used for comparison. Water kefir demonstrated great ability to DPPH scavenging ranged (9.88-63.17%. And inhibit ascorbate oxidation by (6.08-25.57% increased in consequent with concentration raising. These results prime to conclude that water kefir could be promisor source of natural antioxidants with good potency in health developing.

  17. From artificial red blood cells, oxygen carriers, and oxygen therapeutics to artificial cells, nanomedicine, and beyond.

    Science.gov (United States)

    Chang, Thomas M S

    2012-06-01

    The first experimental artificial red blood cells have all three major functions of red blood cells (rbc). However, the first practical one is a simple polyhemoglobin (PolyHb) that only has an oxygen-carrying function. This is now in routine clinical use in South Africa and Russia. An oxygen carrier with antioxidant functions, PolyHb-catalase-superoxide dismutase, can fulfill two of the three functions of rbc. Even more complete is one with all three functions of rbc in the form of PolyHb-catalase-superoxide dismutase-carbonic anhydrase. The most advanced ones are nanodimension artificial rbc with either PEG-lipid membrane or PEG-PLA polymer membrane. Extensions into oxygen therapeutics include a PolyHb-tyrosinase that suppresses the growth of melanoma in a mice model. Another is a PolyHb-fibrinogen that is an oxygen carrier with platelet-like function. Research has now extended well beyond the original research on artificial rbc into many areas of artificial cells. These include nanoparticles, nanotubules, lipid vesicles, liposomes, polymer-tethered lipid vesicles, polymersomes, microcapsules, bioencapsulation, nanocapules, macroencapsulation, synthetic cells, and others. These are being used in nanotechnology, nanomedicine, regenerative medicine, enzyme/gene therapy, cell/stem cell therapy, biotechnology, drug delivery, hemoperfusion, nanosensers, and even by some groups in agriculture, industry, aquatic culture, nanocomputers, and nanorobotics.

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

    Directory of Open Access Journals (Sweden)

    Sadia Afrin

    2016-01-01

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

  19. Hydrophilic and lipophilic antioxidant activities of guava fruits.

    Science.gov (United States)

    Thaipong, Kriengsak; Boonprakob, Unaroj; Cisneros-Zevallos, Luis; Byrne, David H

    2005-01-01

    The objectives of this study were to evaluate the hydrophilic antioxidant activity (AOAH) and the lipophilic antioxidant activity (AOAL); and their correlations with vitamin C, and total phenolic and beta-carotene contents in fresh guava fruits of one white flesh clone ('Allahabad Safeda') and three pink flesh clones ('Fan Retief', 'Ruby Supreme,' and an advanced selection). A ferric reducing antioxidant power assay was used to estimate both AOAH and AOAL from methanol and dichloromethane extracts, respectively. The white flesh clone, 'Allahabad Safeda,' showed higher levels of both AOAH [33.3 microM Trolox equivalents (TE)/g fresh weight (FW)] and AOAL (0.25 microM TE/g FW) than the pink flesh clones that ranged from 15.5 to 30.4 and from 0.12 to 0.13 microM TE/g FW for AOAH and AOAL, respectively. The AOAH was positively correlated with vitamin C (r = 0.92, p < 0.01) and total phenolic (r = 0.97, p < 0.01) but was negatively correlated with beta-carotene (r = -0.73, p = 0.03). The AOAL was not correlated with these antioxidants.

  20. Enzyme-Enhanced Extraction of Antioxidant Ingredients from Algae.

    Science.gov (United States)

    Adalbjörnsson, Björn V; Jónsdóttir, Rósa

    2015-01-01

    Marine algae are not only a rich source of dietary fibre, proteins, vitamins, and minerals, but also contain a great variety of secondary metabolites with diverse biological activities. Marine macroalgae are a rich source of various natural antioxidants such as polyphenols, especially phlorotannins (made of polyphloroglucinol units) derived from brown algae, which play an important role in preventing lipid peroxidation. In recent years, a number of potent antioxidant compounds have been isolated and identified from different types of edible seaweeds. Extraction methods commonly used for the isolation of antioxidants are based on conventional water or organic solvent extractions. However, recent advances have shown that enzymatic hydrolysis can achieve higher yield of bioactive compounds from algae. Here we describe a method based on enzymatic hydrolysis which both increases yield and decreases cost associated with organic solvents. This method achieves cell wall disruption and breakdown of internal storage components for more effective release of intracellular bioactive compounds. In addition, hydrolysis of proteins produces peptides which may have antioxidant properties, thus enhancing the bioactivity of the algal extract. The method described can be used for production of extracts from red and brown macroalgal species.

  1. Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

    Science.gov (United States)

    Bhullar, Khushwant S.; Rupasinghe, H. P. Vasantha

    2013-01-01

    Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders. PMID:23840922

  2. [Studying the mechanism of antioxidant effect of vitamins and flavonoids].

    Science.gov (United States)

    Makarov, V G; Makarova, M N; Selezneva, A I

    2005-01-01

    In work antiradical activity of vitamins and flafonoids in relation to hydroxyl radical is established. The most antiradical activity is established for flavonoids quercetin, routin, daidzein, biochanin A and luteolin-7glucosid, Among vitamins of group in the most antiradical activity have shown vitamins B12, B2, B5, Bc. In group of fat-soluble vitamins ascorbic palmitat, vitamin K1, vitamin A and beta-carotin have shown activity above, than a known antioxidant vitamin E. The carried out work allows to draw a conclusion that antiradical activity in the relation hydroxyl radical shows the broad audience of vitamins that probably is one of aspects of their therapeutic action.

  3. Overview of Nrf2 as Therapeutic Target in Epilepsy

    Directory of Open Access Journals (Sweden)

    Liliana Carmona-Aparicio

    2015-08-01

    Full Text Available Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2, which plays a central role in the regulation of antioxidant response elements (ARE and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.

  4. Particulate Systems for Targeting of Macrophages: Basic and Therapeutic Concepts

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moien; Parhamifar, Ladan; Ahmadvand, Davoud

    2012-01-01

    Particulate systems in the form of liposomes, polymeric micelles, polymeric nano- and microparticles, and many others offer a rational approach for selective delivery of therapeutic agents to the macrophage from different physiological portals of entry. Particulate targeting of macrophages and in...... at a particular subset of macrophages. Advances in basic and therapeutic concepts of particulate targeting of macrophages and related nanotechnology approaches for immune cell modifications are discussed.Copyright © 2012 S. Karger AG, Basel...

  5. Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

    Directory of Open Access Journals (Sweden)

    Shuaijian Ni

    2017-08-01

    Full Text Available Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics.

  6. The anti-oxidant effects of melatonin derivatives on human gingival fibroblasts.

    Science.gov (United States)

    Phiphatwatcharaded, Chawapon; Puthongking, Ploenthip; Chaiyarit, Ponlatham; Johns, Nutjaree Pratheepawanit; Sakolchai, Sumon; Mahakunakorn, Pramote

    2017-07-01

    Aim of this in vitro study was to evaluate the anti-oxidant activity of indole ring modified melatonin derivatives as compared with melatonin in primary human gingival fibroblast (HGF) cells. Anti-oxidant activity of melatonin (MLT), acetyl-melatonin (AMLT) and benzoyl-melatonin (BMLT) was evaluated by5 standard methods as follows: 2, 2-diphenyl-1-picrylhydrazyl (DPPH); ferric ion reducing antioxidant power (FRAP); superoxide anion scavenging; nitric oxide (NO) scavenging; and thiobarbituric acid reactive substances (TBARs).Evaluation of cellular antioxidant activity (CAA) and protectivity against H 2 O 2 induced cellular damage was performed via MTT assay in HGF cells. According to the standard anti-oxidant assays, the antioxidant power of AMLT and BMLT were slightly less than MLT in FRAP and superoxide scavenging assays. In the NO scavenging and TBARs assays, BMLT and AMLT were more potent than MLT, whereas DPPH assays demonstrated that MLT was more potent than others. BMLT and AMLT had more potent anti-oxidant and protective activities against H 2 O 2 in HGF cells as compared with MLT. MLT derivatives demonstrated different anti-oxidant activities as compared with MLT, depending upon assays. These findings imply that N-indole substitution of MLT may help to improve hydrogen atom transfer to free radicals but electron transfer property is slightly decreased. Anti-oxidant and protective effects of melatonin derivatives (AMLT and BMLT) on human gingival fibroblasts imply the potential use of these molecules as alternative therapeutics for chronic inflammatory oral diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effect of growth stages on total phenolics content and antioxidant activity of Fumaria vaillantii L.

    Directory of Open Access Journals (Sweden)

    L. Mehdizadeh*

    2017-11-01

    Full Text Available Background and objectives: Plant extracts and their constituents are known to exert biological effects, especially antioxidant activity. Fumaria vaillantii (Fumariaceae has several therapeutic effects in traditional medicine. Antioxidants are able to protect the human body from oxidative damage connected to the reaction of free radicals. Synthetic antioxidants have toxic and carcinogenic effects on human health; therefore, their application has been limited. Thus, there has been an increasing interest in the natural antioxidant compounds to prevent the foods from deterioration. In this study, the antioxidant activity of F. vaillantii extracts at three stages of growth has been evaluated. Methods: The ethanol extracts from the aerial parts of the plants at different phenological stages were prepared and the total phenolics content was determined by Folin-Ciocalteu reagent. Also, the antioxidant activity were determined by three methods as 2,2-diphenyl-1-picrylhydrazyl (DPPH, ferric-ion reducing antioxidant power (FRAP and phosphomolybdenum complex tests. All experiments were carried out in triplicate, and data were subjected to ANOVA according to the SAS software. Results: Total phenolics content of vegetative, budding and flowering stages were 68.38, 71.11 and 56.42 mg GAE/g extract, respectively. Although flowering stage showed the highest antioxidant activity in phosphomolybdenum complex, in DPPH and FRAP methods, it decreased from vegetative to flowering stages. Conclusion: According to the results, the Iranian F. vaillantii extract from vegetative stage was a potential source of natural antioxidants for food and pharmaceutical industries that can be used in different industries.

  8. The proper time for antioxidant consumption.

    Science.gov (United States)

    Beaulieu, Michaël; Schaefer, H Martin

    2014-04-10

    Consuming food rich in antioxidants may help organisms to increase their antioxidant defences and avoid oxidative damage. Under the hypothesis that organisms actively consume food for its antioxidant properties, they would need to do so in view of other physiological requirements, such as energy requirements. Here, we observed that Gouldian finches (Erythrura gouldiae) consumed most seeds rich in antioxidants in the middle of the day, while their consumption of staple seeds more profitable in energy intake (and poor in antioxidants) was maximal in the morning and the evening. This consumption of seeds rich in antioxidants in the middle of the day may be explicable (1) because birds took advantage of a time window associated with relaxed energy requirements to ingest antioxidant resources, or (2) because birds consumed antioxidant resources as a response to the highest antioxidant requirements in the middle of the day. If the latter hypothesis holds true, having the possibility to ingest antioxidants should be most beneficial in terms of oxidative balance in the middle of the day. Even though feeding on seeds rich in antioxidants improved Gouldian finches' overall antioxidant capacity, we did not detect any diurnal effect of antioxidant intake on plasma oxidative markers (as measured by the d-ROM and the OXY-adsorbent tests). This indicates that the diurnal pattern of antioxidant intake that we observed was most likely constrained by the high consumption of staple food to replenish or build up body reserves in the morning and in the evening, and not primarily determined by elevated antioxidant requirements in the middle of the day. Consequently, animals appear to have the possibility to increase antioxidant defences by selecting food rich in antioxidants, only when energetic constraints are relaxed. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. New concepts in therapeutic photomedicine: photochemistry, optical targeting and the therapeutic window

    International Nuclear Information System (INIS)

    Parrish, J.A.

    1981-01-01

    Advances in optics technology, synthetic photochemistry, and the science of photobiology make it possible to think beyond phototherapy and photochemotherapy which is dependent on direct photochemical alteration of metabolites or direct phototoxic insult to cells. This report discusses another gender of photomedicine therapy which includes in vivo photoactivation of medicines, photon-dependent drug delivery, and manipulation of host and exposure source to maximize therapeutic index. These therapeutic manipulations are made possible because the skin is highly overperfused and because non-ionizing electromagnetic radiation that enters skin and blood has adequate photon energy to cause electronic excitation. Radiation of 320-800 nm is not very directly phototoxic, is absorbed by a variety of relatively nontoxic photolabile molecules and has an internal dosimetric depth profile. This radiation can therefore be used to activate, deactivate, bind, release or biotransform medications in vivo in skin or other organs. The photochemist, synthetic chemist and photobiologist can collaborate to significantly increase therapeutic possibilities

  10. Therapeutic Advances using Combinational Therapy in the Treatment of Glioblastoma

    DEFF Research Database (Denmark)

    Staberg, Mikkel

    2017-01-01

    Glioblastoma is the most malignant brain tumor in adults. Median survival is only about 15 months despite aggressive treatment, consisting of surgery followed by radio- and chemotherapy, stressing the need for new therapies. Development of glioblastoma is thought to be a result of both genetic...... of glioblastoma cells, an effect that is even more pronounced when combined with traditional chemotherapeutic agents. The EGFR and Notch pathways are shown to be of great importance for glioblastoma cell survival and for the formation of new blood vessels, a process known as angiogenesis. Results presented herein...... suggests that targeting redundant signaling pathways can overcome required or initial treatment resistance, thus leading to improved tumor cell elimination. We hypothesize that future therapies will likely be a result of combination therapies for glioblastoma patients based on their molecular tumor profile...

  11. A Novel Therapeutic Modality for Advanced Stage Prostate Cancer Treatment

    Science.gov (United States)

    2017-10-01

    Successful examples of drugs repurposing are anti- diabetic drug metformin and the birth control hormone medroxyprogesterone acetate . In this study...membrane potential (Dym), we utilized tetramethyl rhodamine ethyl ester (TMRE) as described (12). Xenograft study A total of 12 athymic nude male mice

  12. Advance of Therapeutic Methods for Malignant Pleural Effusion

    Directory of Open Access Journals (Sweden)

    Tao-tao XU

    2016-06-01

    Full Text Available Malignant pleural effusion (MPE is a condition caused by primary malignant tumors in the pleura or other malignant tumors metastasis to the pleura. It is also one of common serious complications of middle-late malignant tumor, which has severe impact on the quality of life, even threatening the life of the patients. The selection of treatments for MPE depends on many factors, including the symptoms, performance status, primary tumor types, response to systemic therapy, and degree of lung recruitment maneuvers (LRM after drainage of pleural effusion. Generally, the treatment methods include thoracentesis, indwelling pleural catheter, pleurodesis, intrapleural injection of drugs, chemotherapy, radiotherapy, anti-angiogenesis therapy, surgery, and thermotherapy. With the in-depth study on pathogenesis of MPE, the treatments of MPE have continuous improvements. This study mainly reviewed the treatment methods for MPE so as to provide the basis for clinical practice in the future.

  13. Special papers Diagnostic and therapeutic advances in dermatomyositis

    Directory of Open Access Journals (Sweden)

    Dominik Samotij

    2015-06-01

    Full Text Available Dermatomyositis (DM is one of the so-called idiopathic inflammatory myopathies (IIM. Dermatomyositis is an autoimmune disorder characterized by the presence of cutaneous lesions and/or symptoms of muscle involvement with the following variants: the “classic” variant of DM, juvenile DM, paraneoplastic DM, drug-induced DM and amyopathic DM. Dynamic discoveries of novel autoantibodies, including anti-TIF1, anti-NXP2, anti-SAE or anti-MDA5, related to certain DM variants, have been described in recent years. It seems that these antibodies will contribute to better recognition of DM and its particular variants, a better risk stratification for predicting internal organ involvement, and to a global improvement of treatment outcome. Corticosteroids remain the mainstay of DM therapy, but new immunomodulatory and immunosuppressive agents, including biologicals, resulted in a significant increase of the survival rate of DM patients. Here, we review the current literature data on DM with special emphasis on new trends in its diagnostics and treatment.

  14. Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics

    Science.gov (United States)

    Kazdoba, Tatiana M.; Leach, Prescott T.; Yang, Mu; Silverman, Jill L.; Solomon, Marjorie

    2016-01-01

    Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism. PMID:27305922

  15. The Antioxidant Therapy: New Insights in the Treatment of Hypertension.

    Science.gov (United States)

    Sorriento, Daniela; De Luca, Nicola; Trimarco, Bruno; Iaccarino, Guido

    2018-01-01

    therapeutics in the management of hypertension. In the present review we have dealt with the effectiveness of the antioxidant therapy in the management of hypertension. In particular, we discuss about Vitamin D and anti-hypertensive drugs with antioxidant properties.

  16. The Antioxidant Therapy: New Insights in the Treatment of Hypertension

    Directory of Open Access Journals (Sweden)

    Daniela Sorriento

    2018-03-01

    considered promising therapeutics in the management of hypertension. In the present review we have dealt with the effectiveness of the antioxidant therapy in the management of hypertension. In particular, we discuss about Vitamin D and anti-hypertensive drugs with antioxidant properties.

  17. Therapeutic potential of cannabinoid medicines.

    Science.gov (United States)

    Robson, P J

    2014-01-01

    Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines. The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology. In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders. Copyright © 2013 John Wiley & Sons, Ltd.

  18. [Achievement of therapeutic objectives].

    Science.gov (United States)

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  19. Therapeutic approaches to cellulite.

    Science.gov (United States)

    Green, Jeremy B; Cohen, Joel L; Kaufman, Joely; Metelitsa, Andrei I; Kaminer, Michael S

    2015-09-01

    Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution. ©2015 Frontline Medical Communications.

  20. Revitalizing Psychiatric Therapeutics

    Science.gov (United States)

    Hyman, Steven E

    2014-01-01

    Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as ‘too difficult' a challenge to warrant major investment. Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials. My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry's concerns. PMID:24317307

  1. [The effect of exogenous antioxidants on the antioxidant status of erythrocytes and hepcidin content in blood of patients with disorders of iron metabolism regulation].

    Science.gov (United States)

    Shcherbinina, S P; Levina, A A; Lisovskaia, I L; Ataullakhanov, F I

    2013-01-01

    In many diseases associated with impairments in iron metabolism, erythrocytes exhibit an increased sensitivity to oxidative stress induced in vitro. In this study, we have examined the antioxidant status of erythrocytes from healthy donors and from 12 patients with disorders of iron homeostasis by measuring the extent of t-BHP-induced hemolysis in vitro. The extent of hemolysis observed with patient erythrocytes was significantly higher than that observed in experiment with normal cells. After therapeutic infusions of the antioxidants mexidol or emoxypin, oxidative hemolysis in patients was restored to normal values and blood hepcidin content increased significantly. A significant correlation was observed between hepcidin concentration after treatment and t-BHP-induced hemolysis before treatment. These data suggest that antioxidants may exert a favorable effect under pathological conditions associated with iron overload disease.

  2. Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress

    Directory of Open Access Journals (Sweden)

    Alexander V. Vavaev

    2012-02-01

    Full Text Available The focus in antioxidant research is on enzyme derivative investigations. Extracellular superoxide dismutase (EC-SOD is of particular interest, as it demonstrates in vivo the protective action against development of atherosclerosis, hypertension, heart failure, diabetes mellitus. The reliable association of coronary artery disease with decreased level of heparin-released EC-SOD was established in clinical research. To create a base for and to develop antioxidant therapy, various SOD isozymes, catalase (CAT, methods of gene therapy, and combined applications of enzymes are used. Covalent bienzyme SOD-CHS-CAT conjugate (CHS, chondroitin sulphate showed high efficacy and safety as the drug candidate. There is an evident trend to use the components of glycocalyx and extracellular matrix for target delivery of medical substances. Development of new enzyme antioxidants for therapeutic application is closely connected with progress in medical biotechnology, pharmaceutical industry, and bioeconomy.

  3. New Therapeutics to Treat Castrate-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ömer Acar

    2013-01-01

    Full Text Available The effective treatment of castrate-resistant prostate cancer (CRPC has proven to be very challenging. Until recently, docetaxel was the only therapeutic demonstrated to extend overall patient survival. Yet recently, a considerable number of new therapeutics have been approved to treat CRPC patients. These remarkable advances now give new tools for the therapeutic management of late-stage prostate cancer. In this review, we will examine mechanistic and clinical data of several newly approved therapeutics including the chemotherapeutic cabazitaxel, antiandrogen enzalutamide, endocrine disruptor abiraterone acetate, immunotherapy sipuleucel-T, and bone-targeting radiopharmaceutical alpharadin. In addition, we will examine other promising therapeutics that are currently in Phase III trials.

  4. Antioxidant and antimicrobial activities of polyphenols from ...

    African Journals Online (AJOL)

    USER

    2010-05-17

    May 17, 2010 ... The antioxidant properties and antimicrobial potential of three ethnomedicinal plants, (Momordica charanta, Senna alata and Nauclea lafifolia) extracted with acetone were investigated. Polyphenols from the medicinal plants were screened for their antioxidant and antimicrobial activities against pathogenic.

  5. Antioxidant and antimicrobial activities of polyphenols from ...

    African Journals Online (AJOL)

    the medicinal plants were screened for their antioxidant and antimicrobial activities against pathogenic micro organisms (Staphylococcus aureus, Streptococcus pyogenes, Esherichia coli and Candida albicans). The medicinal plants displayed different polyphenols contents and antioxidant activities. In addition, varying ...

  6. Proximate and Phytochemical composition and antioxidant ...

    African Journals Online (AJOL)

    Conclusion: Indigenous landraces of Omani fenugreek seeds are a rich source of protein, dietary fiber, and many important bioactive components, which were found to be significantly correlatedwith its antioxidant properties. Keywords: Omani fenugreek, landraces, phytochemical composition, antioxidant properties.

  7. Antioxidant and antibacterial activities of polyphenols from ...

    African Journals Online (AJOL)

    Polyphenols from four medicinal plants of Burkina Faso, Combretum micranthum, Khaya senegalensis, Pterocarpus erinaceus and Sida acuta, were screened for their antioxidant and antimicrobial activities against pathogenic bacteria. The medicinal plants displayed different polyphenols contents and antioxidant activities.

  8. Antioxidant food supplements in human health

    National Research Council Canada - National Science Library

    Hiramatsu, Midori; Packer, Lester; Yoshikawa, Toshikazu

    1999-01-01

    ... of many of nature's antioxidant substances; grapes: starting source for red wine production; rich in antioxidants; onions: rich source of the bioflavonoid quercetin. This book is printed on acid-...

  9. Cosmeceutical values, antimicrobial activities and antioxidant ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... Key words: Antimicrobial, antioxidant, ethanol extract, water extract, cashew leaves, cosmeceutical. INTRODUCTION ... Anacardium occidentale (Cashew) leaves extract could ..... Antioxidant activity at different contact time for treatment of different concentration CLE in water with different amount of GAC.

  10. Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yau-Chuk Cheuk

    2017-01-01

    Conclusion: Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.

  11. Antioxidant properties of catechins: Comparison with other antioxidants.

    Science.gov (United States)

    Grzesik, Michalina; Naparło, Katarzyna; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2018-02-15

    Antioxidant properties of five catechins and five other flavonoids were compared with several other natural and synthetic compounds and related to glutathione and ascorbate as key endogenous antioxidants in several in vitro tests and assays involving erythrocytes. Catechins showed the highest ABTS-scavenging capacity, the highest stoichiometry of Fe 3+ reduction in the FRAP assay and belonged to the most efficient compounds in protection against SIN-1 induced oxidation of dihydrorhodamine 123, AAPH-induced fluorescein bleaching and hypochlorite-induced fluorescein bleaching. Glutathione and ascorbate were less effective. (+)-catechin and (-)-epicatechin were the most effective compounds in protection against AAPH-induced erythrocyte hemolysis while (-)-epicatechin gallate, (-)-epigallocatechin gallate and (-)-epigallocatechin protected at lowest concentrations against hypochlorite-induced hemolysis. Catechins [(-)-epigallocatechin gallate and (-)-epicatechin gallate)] were most efficient in the inhibition of AAPH-induced oxidation of 2'7'-dichlorodihydroflurescein contained inside erythrocytes. Excellent antioxidant properties of catechins and other flavonoids make them ideal candidates for nanoformulations to be used in antioxidant therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when ev...

  13. Oxidative Stress: A Unifying Mechanism for Cell Damage Induced by Noise, (Water-Pipe) Smoking, and Emotional Stress-Therapeutic Strategies Targeting Redox Imbalance.

    Science.gov (United States)

    Golbidi, Saeid; Li, Huige; Laher, Ismail

    2018-03-20

    Modern technologies have eased our lives but these conveniences can impact our lifestyles in destructive ways. Noise pollution, mental stresses, and smoking (as a stress-relieving solution) are some environmental hazards that affect our well-being and healthcare budgets. Scrutinizing their pathophysiology could lead to solutions to reduce their harmful effects. Recent Advances: Oxidative stress plays an important role in initiating local and systemic inflammation after noise pollution, mental stress, and smoking. Lipid peroxidation and release of lysolipid by-products, disturbance in activation and function of nuclear factor erythroid 2-related factor 2 (Nrf2), induction of stress hormones and their secondary effects on intracellular kinases, and dysregulation of intracellular Ca 2+ can all potentially trigger other vicious cycles. Recent clinical data suggest that boosting the antioxidant system through nonpharmacological measures, for example, lifestyle changes that include exercise have benefits that cannot easily be achieved with pharmacological interventions alone. Indiscriminate manipulation of the cellular redox network could lead to a new series of ailments. An ideal approach requires meticulous scrutiny of redox balance mechanisms for individual pathologies so as to create new treatment strategies that target key pathways while minimizing side effects. Extrapolating our understanding of redox balance to other debilitating conditions such as diabetes and the metabolic syndrome could potentially lead to devising a unifying therapeutic strategy. Antioxid. Redox Signal. 28, 741-759.

  14. Genome Engineering for Personalized Arthritis Therapeutics.

    Science.gov (United States)

    Adkar, Shaunak S; Brunger, Jonathan M; Willard, Vincent P; Wu, Chia-Lung; Gersbach, Charles A; Guilak, Farshid

    2017-10-01

    Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Antioxidants: Characterization, natural sources, extraction and analysis

    OpenAIRE

    OROIAN, MIRCEA; Escriche Roberto, Mª Isabel

    2015-01-01

    [EN] Recently many review papers regarding antioxidants fromdifferent sources and different extraction and quantification procedures have been published. However none of them has all the information regarding antioxidants (chemistry, sources, extraction and quantification). This article tries to take a different perspective on antioxidants for the new researcher involved in this field. Antioxidants from fruit, vegetables and beverages play an important role in human health, fo...

  16. Partitioning of selected antioxidants in mayonnaise

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte; Schwarz, K.; Stockmann, H.

    1999-01-01

    This study examined partitioning of alpha-, beta-, and gamma- tocopherol and six polar antioxidants (Trolox, ferulic acid, caffeic acid, propyl gallate, gallic acid, and catechin) in mayonnaise. Partitioning of antioxidants between different phases was determined after separation of mayonnaise...... by either (a) centrifugation + ultracentrifugation or (b) centrifugation + dialysis. Antioxidants partitioned in accordance with their chemical structure and polarity: Tocopherols were concentrated in the oil phase (93-96%), while the proportion of polar antioxidants in the oil phase ranged from 0% (gallic...

  17. Antiradical and antioxidant activities of new bio-antioxidants.

    Science.gov (United States)

    Kancheva, V D; Saso, L; Angelova, S E; Foti, M C; Slavova-Kasakova, A; Daquino, C; Enchev, V; Firuzi, O; Nechev, J

    2012-02-01

    Antioxidants could be promising agents for management of oxidative stress-related diseases. New biologically active compounds, belonging to a rare class of natural lignans with antiangiogenic, antitumoral and DNA intercalating properties, have been recently synthesized. These compounds are benzo[kl]xanthene lignans (1,2) and dihydrobenzofuran neolignans (3,4). The radical scavenging and chain-breaking antioxidant activities of compounds 1-4 were studied by applying different methods: radical scavenging activity by DPPH rapid test, chain-breaking antioxidant activity and quantum chemical calculations. All studied compounds were found to be active as DPPH scavengers but reaction time with DPPH and compounds' concentrations influenced deeply the evaluation. The highest values of radical scavenging activity (%RSAmax) and largest rate constants for reaction with DPPH were obtained for compounds 2 and 3. Comparison of %RSAmax with that of standard antioxidants DL-α-tocopherol (TOH), caffeic acid (CA) and butylated hydroxyl toluene (BHT) give the following new order of %RSA max: TOH (61.1%) > CA (58.6%) > 3 (36.3%) > 2 (28.1%) > 4 (6.7%) > 1 (3.6%) = BHT (3.6%). Chain-breaking antioxidant activities of individual compounds (0.1-1.0 mM) and of their equimolar binary mixtures (0.1 mM) with TOH were determined from the kinetic curves of lipid autoxidation at 80 °C. On the basis of a comparable kinetic analysis with standard antioxidants a new order of the antioxidant efficiency (i.e., protection factor, PF) of compounds 1-4 were obtained: 2 (7.2) ≥ TOH (7.0) ≥ CA (6.7) > 1 (3.1) > 3 (2.2) > ferulic acid FA (1.5) > 4 (0.6); and of the antioxidant reactivity (i.e. inhibition degree, ID): 2 (44.0) > TOH (18.7) > CA (9.3) > 1 (8.4) > 3 (2.8) > FA (1.0) > 4 (0.9). The important role of the catecholic structure in these compounds, which is responsible for the high chain-breaking antioxidant activity, is discussed and a reaction

  18. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  19. Therapeutic nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Baum, Richard P. (ed.) [ENETS Center of Excellence, Bad Berka (Germany). THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging

    2014-07-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  20. Therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Baum, Richard P.

    2014-01-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  1. [Hemoglobinopathies. Current therapeutic possibilities].

    Science.gov (United States)

    Birgens, H S; Karle, H

    1995-05-29

    In recent years, the number of immigrants has increased considerably in Denmark. Consequently, a series of new clinical pictures has appeared in the Danish health care system. Typical examples are the genetic diseases, the haemoglobinopathies. Most of the immigrants come from areas, where the gene frequency of these disorders is widely distributed, for instance the Mediterranean countries, the Middle East, Southeast Asia and Africa. Most frequent are the heterozygous thalassaemias, but also the number of patients with severe thalassaemia and other clinically important haemoglobinopathies such as sickle cell anaemia has also increased in recent years. The clinical problems concerning these patients focus on two important topics, namely genetic counselling of heterozygous individuals (in some cases combined with prenatal diagnostics) and the treatment of patients with clinically severe haemoglobinopathy. The only curative treatment of the haemoglobinopathies is allogeneic bone marrow transplantation, but this treatment can only be offered to a few of these patients. However, a variety of therapeutic options exist which can improve their prognosis and quality of life. Since the number of patients with these diseases will probably increase over the next years we find it relevant, based on typical case stories, to give a review of the present therapeutic possibilities for these disorders.

  2. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  3. Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers.

    Science.gov (United States)

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2016-07-01

    Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma

  4. Streptomyces sp. MUM212 as a Source of Antioxidants with Radical Scavenging and Metal Chelating Properties

    Directory of Open Access Journals (Sweden)

    Loh Teng-Hern Tan

    2017-05-01

    Full Text Available Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants. Strain MUM212 was characterized and determined as belonging to the genus Streptomyces using 16S rRNA gene phylogenetic analysis. The MUM212 extract demonstrated significant antioxidant activity through DPPH, ABTS and superoxide radical scavenging assays and also metal-chelating activity of 22.03 ± 3.01%, 61.52 ± 3.13%, 37.47 ± 1.79%, and 41.98 ± 0.73% at 4 mg/mL, respectively. Moreover, MUM212 extract was demonstrated to inhibit lipid peroxidation up to 16.72 ± 2.64% at 4 mg/mL and restore survival of Vero cells from H2O2-induced oxidative damages. The antioxidant activities from the MUM212 extract correlated well with its total phenolic contents; and this in turn was in keeping with the gas chromatography–mass spectrometry analysis which revealed the presence of phenolic compounds that could be responsible for the antioxidant properties of the extract. Other chemical constituents detected included hydrocarbons, alcohols and cyclic dipeptides which may have contributed to the overall antioxidant capacity of MUM212 extract. As a whole, strain MUM212 seems to have potential as a promising source of novel molecules for future development of antioxidative therapeutic agents against oxidative stress-related diseases.

  5. In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

    Science.gov (United States)

    Martinčič, Rok; Mravljak, Janez; Švajger, Urban; Perdih, Andrej; Anderluh, Marko; Novič, Marjana

    2015-01-01

    A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.

  6. In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

    Directory of Open Access Journals (Sweden)

    Rok Martinčič

    Full Text Available A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.

  7. Evaluation of phenolic content and antioxidant potency in various parts of Cassia auriculata L.: a traditionally valued plant.

    Science.gov (United States)

    Purushotham, K N; Annegowda, H V; Sathish, N K; Ramesh, B; Mansor, S M

    2014-01-01

    Presence of polyphenolic content in various part of the plant exhibit wide pharmacological activities including antioxidant activity. The present study was designed to evaluate the phenolic contents (total phenols, flavonoid and tannins) and antioxidant properties of ethanolic extracts of flower, leaf, pod, bark and root obtained from Cassia auriculata. Ethanolic extracts of various parts of C. auriculata obtained by sonication extraction techniques are studied for their phenolic contents and DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging assay as well as total antioxidant assays using UV visible spectrophotometer. Among the various parts of the plant studied, bark showed significant content of phenolics, flavonoids and tannins followed by the root, leaf, flower and pod. Even bark extract exhibited highest antioxidant capacity in DPPH assay followed by root, leaf, flower and pod with a value of 766.7, 679.3, 644.9, 572.5 and 474.7 mg vitamin C equivalent antioxidant capacity (mg VCEAC)/sample, respectively. In addition, mg VCEAC values obtained from the total antioxidant assay was in the increasing order of bark > root > leaf > flower > pod. Moreover, a strong correlation was also found between phenolic contents and antioxidant values indicating their influence in the found antioxidant activity, hence the bark extract can be employed as an ideal candidate for herbal based pharmaceutical product. Results of the present study also emphasize variation in the chemical composition as well as biological activity ensuring the importance of proper selection of particular part of the plant to evaluate their therapeutic potency.

  8. 21 CFR 181.24 - Antioxidants.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Antioxidants. 181.24 Section 181.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Antioxidants. Substances classified as antioxidants, when migrating from food-packaging material (limit of...

  9. Analysis of Two Methods to Evaluate Antioxidants

    Science.gov (United States)

    Tomasina, Florencia; Carabio, Claudio; Celano, Laura; Thomson, Leonor

    2012-01-01

    This exercise is intended to introduce undergraduate biochemistry students to the analysis of antioxidants as a biotechnological tool. In addition, some statistical resources will also be used and discussed. Antioxidants play an important metabolic role, preventing oxidative stress-mediated cell and tissue injury. Knowing the antioxidant content…

  10. Flavonoid, hesperidine, total phenolic contents and antioxidant ...

    African Journals Online (AJOL)

    Additionally, the antioxidant activities were also determined by ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity. C. hystrix had the highest flavonoid and total phenolic contents while C. aurantifolia had the highest hesperidine content. The antioxidant activity of ...

  11. Total Antioxidant Capacity, Polyphenolic composition and ...

    African Journals Online (AJOL)

    The growing interest in the substitution of synthetic food antioxidants with natural ones in the maintenance of human health has fostered increased research on the screening of plants for the identification of antioxidants. The total antioxidant capacity and polyphenolic content of the extracts of the three varieties of rizga flour ...

  12. Antioxidants in bakery products: a review.

    Science.gov (United States)

    Nanditha, B; Prabhasankar, P

    2009-01-01

    Fats impart taste and texture to the product but it is susceptible to oxidation leading to the development of rancidity and off-flavor. Since ancient times it has been in practice to use antioxidants in foods. Discovery of synthetic antioxidants has revolutionized the use of antioxidants in food. The effect of these antioxidants in bakery products were reviewed and found to be effective in enhancing the shelf life. Animal experimental studies have shown that some of the synthetic antioxidants had toxigenic, mutagenic, and carcinogenic effects. Hence there is an increasing demand for the use of natural antioxidants in foods, especially in bakery products. Some of the natural antioxidants such as alpha-tocopherol, beta-carotene, and ascorbic acid were already used in bakery products. These natural antioxidants are found to be effective in enhancing the shelf life of bakery products but not to the extent of synthetic antioxidants. Baking processing steps may lower the antioxidative activity but techniques such as encapsulation of antioxidants can retain their activity. Antioxidative activity of the plant extracts such as garcinia, curcumin, vanillins, and mint were reviewed but studies on their role in bakery products were limited or very few. Hence there is a wide scope for study under this direction in depth.

  13. Interaction of phenolic antioxidants and hydroxyl radicals

    International Nuclear Information System (INIS)

    Wang, W.F.; Luo, J.; Yao, S.D.; Lian, Z.R.; Zhang, J.S.; Lin, N.Y.

    1993-01-01

    Based on pulse radiolysis of aqueous solutions of four phenolic antioxidants including green tea polyphenols, quercetin, caffeic acid and sinapic acid the rate constants for reactions of OH and the antioxidants were determined. Green tea polyphenols and quercetin are the strongest antioxidants. (author)

  14. Interaction of phenolic antioxidants and hydroxyl radicals

    International Nuclear Information System (INIS)

    Wang Wenfeng; Luo Jian; Yao Side; Lian Zhirui; Zhang Jiashan; Lin Nianyun

    1992-01-01

    Based on pulse radiolysis of aqueous solutions of four phenolic antioxidants including green tea polyphenols, quercetin, caffeic acid and sinapic acid the rate constants for reactions of OH and the antioxidants were determined. And green tea polyphenols and quercetin are the strongest antioxidants

  15. Comparative Antioxidant, Antiproliferative and Apoptotic Effects of ...

    African Journals Online (AJOL)

    Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina and Ilex paraguariensis in colon cancer cells. Methods: Antioxidant activity was determined by ORAC (Oxygen Radical Absorbance Capacity) and FRAP (Ferric Reducing Antioxidant Power). Cytotoxic ...

  16. Isolation of 62 kda protein with antioxidant properties from natural honey

    International Nuclear Information System (INIS)

    Mohammed, S.E.A.R.

    2014-01-01

    Fourteen natural honey samples from Libya, Sudan and Pakistan were evaluated for their antioxidant activity by employing 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical assay. The scavenging activity of honey samples were in the range of 18-32% when compared to control. A 62 kDa protein was isolated from honey by gel filtration chromatography followed by reverse phase HPLC showed significant radical scavenging activity. The research pointed out the antioxidative role of honey proteins and possibility of their contribution to the therapeutic value of the natural honey. (author)

  17. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review.

    Science.gov (United States)

    Cör, Darija; Knez, Željko; Knez Hrnčič, Maša

    2018-03-13

    Ganoderma lucidum (Reishi) is a popular medicinal mushroom and has been used in oriental medicine because of its promoting effects on health and life expectancy. G. lucidum contains various compounds with a high grade of biological activty, which increase the immunity and show antitumour, antimicrobial, anti-inflammatory, antioxidant and acetylcholinesterase inhibitory activity. Several of these substances belong to the triterpenoids and polysaccharides classes. Proteins, lipids, phenols, sterols, etc. are also present. In the present review, an extensive overview of the presence of antitumour, antimicrobial, antioxidant and antiacetylcholinesterase compounds in G. lucidum extracts will be given, along with an evaluation of their therapeutic effects.

  18. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review

    Directory of Open Access Journals (Sweden)

    Darija Cör

    2018-03-01

    Full Text Available Ganoderma lucidum (Reishi is a popular medicinal mushroom and has been used in oriental medicine because of its promoting effects on health and life expectancy. G. lucidum contains various compounds with a high grade of biological activty, which increase the immunity and show antitumour, antimicrobial, anti-inflammatory, antioxidant and acetylcholinesterase inhibitory activity. Several of these substances belong to the triterpenoids and polysaccharides classes. Proteins, lipids, phenols, sterols, etc. are also present. In the present review, an extensive overview of the presence of antitumour, antimicrobial, antioxidant and antiacetylcholinesterase compounds in G. lucidum extracts will be given, along with an evaluation of their therapeutic effects.

  19. Polysaccharide-based biomaterials with antimicrobial and antioxidant properties

    Directory of Open Access Journals (Sweden)

    Véronique Coma

    2013-01-01

    Full Text Available Active packaging is one of the responses to the recent food-borne microbial outbreaks and to the consumer’s demand for high quality food and for packaging that is more advanced and creative than what is currently offered. Moreover, with the recent increase in ecological awareness associated with the dramatic decrease in fossil resources, research has turned towards the elaboration of more natural materials. This paper provides a short review of biomaterials exhibiting antimicrobial and antioxidant properties for applications in food preservation. The two main concepts of active biopackaging materials are briefly introduced. The different polysaccharides potentially used in packaging materials are then presented associated with a brief overview of research works related to biopackaging, exhibiting notably antimicrobial or antioxidant properties. Finally, future trends such as the release-on-demand of bioactive agents are discussed.

  20. Antioxidant therapies in traumatic brain injury: a review

    Directory of Open Access Journals (Sweden)

    Romero-Rivera Hector Rolando

    2017-09-01

    Full Text Available Oxidative stress constitute one of the commonest mechanism of the secondary injury contributing to neuronal death in traumatic brain injury cases. The oxidative stress induced secondary injury blockade may be considered as to be a good alternative to improve the outcome of traumatic brain injury (TBI treatment. Due to absence of definitive therapy of traumatic brain injury has forced researcher to utilize unconventional therapies and its roles investigated in the improvement of management and outcome in recent year. Antioxidant therapies are proven effective in many preclinical studies and encouraging results and the role of antioxidant mediaction may act as further advancement in the traumatic brain injury management it may represent aonr of newer moadlaity in neurosurgical aramamentorium, this kind of therapy could be a good alternative or adjuct to the previously established neuroprotection agents in TBI.

  1. Advances in biomedical engineering

    CERN Document Server

    Brown, J H U

    1976-01-01

    Advances in Biomedical Engineering, Volume 5, is a collection of papers that deals with application of the principles and practices of engineering to basic and applied biomedical research, development, and the delivery of health care. The papers also describe breakthroughs in health improvements, as well as basic research that have been accomplished through clinical applications. One paper examines engineering principles and practices that can be applied in developing therapeutic systems by a controlled delivery system in drug dosage. Another paper examines the physiological and materials vari

  2. Maca polysaccharides: A review of compositions, isolation, therapeutics and prospects.

    Science.gov (United States)

    Li, Yujuan; Xu, Fangxue; Zheng, Mengmeng; Xi, Xiaozhi; Cui, Xiaowei; Han, Chunchao

    2018-05-01

    Maca polysaccharides, some of the major bioactive substances in Lepidium meyenii (Walp.) (Maca), have various biological properties, including anti-oxidant, anti-fatigue, anti-tumor, and immunomodulatory effects, as well as hepatoprotective activity and regulation function. Although many therapeutics depend on multiple structures of maca polysaccharides in addition to providing sufficient foundations for maca polysaccharide products in industrial applications, the relationships between the pharmacological effects and structures have not been established. Therefore, this article summarizes the extraction and purification methods, compositions, pharmacological effects, prospects and industrial applications of maca polysaccharides. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Oxidative stress and the antioxidant enzyme system in the developing brain

    Directory of Open Access Journals (Sweden)

    So-Yeon Shim

    2013-03-01

    Full Text Available Preterm infants are vulnerable to the oxidative stress due to the production of large amounts of free radicals, antioxidant system insufficiency, and immature oligodendroglial cells. Reactive oxygen species (ROS play a pivotal role in the development of periventricular leukomalacia. The three most common ROS are superoxide (O2&#8226;-, hydroxyl radical (OH&#8226;, and hydrogen peroxide (H2O2. Under normal physiological conditions, a balance is maintained between the production of ROS and the capacity of the antioxidant enzyme system. However, if this balance breaks down, ROS can exert toxic effects. Superoxide dismutase, glutathione peroxidase, and catalase are considered the classical antioxidant enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx, is also an important scavenger of free radicals. Prdx1 expression is induced at birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is consistent with the classical antioxidant enzymes. Several antioxidant substances have been studied as potential therapeutic agents; however, further preclinical and clinical studies are required before allowing clinical application.

  4. Protective Effect of Antioxidants on Neuronal Dysfunction and Plasticity in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Thirunavukkarasu Velusamy

    2017-01-01

    Full Text Available Huntington’s disease (HD is characterised by movement disorders, cognitive impairments, and psychiatric problems. The abnormal generation of reactive oxygen species and the resulting oxidative stress-induced mitochondrial damage in neurons upon CAG mutations in the HTT gene have been hypothesized as the contributing factors of neurodegeneration in HD. The potential use of antioxidants against free radical toxicity has been an emerging field in the management of ageing and many neurodegenerative disorders. Neural stem cells derived adult neurogenesis represents the regenerative capacity of the adult brain. The process of adult neurogenesis has been implicated in the cognitive functions of the brain and is highly modulated positively by different factors including antioxidants. The supportive role of antioxidants to reduce the severity of HD via promoting the functional neurogenesis and neuroprotection in the pathological adult brain has great promise. This review comprehends the recent studies describing the therapeutic roles of antioxidants in HD and other neurologic disorders and highlights the scope of using antioxidants to promote adult neurogenesis in HD. It also advocates a new line of research to delineate the mechanisms by which antioxidants promote adult neurogenesis in HD.

  5. Study on preparation of new antioxidants for radiation vulcanized natural rubber latex product. Antioxidant from keratin

    International Nuclear Information System (INIS)

    Nguyen Quoc Hien; Nguyen Van Toan; Vo Tan Thien; Le Hai

    2000-01-01

    The thermo-oxidative aging resistance of radiation vulcanization of natural rubber latex (RVNRL) products should be adequately by using suitable antioxidants or new kind of effective antioxidant. This work presents the results of preparation of natural antioxidant from hair keratin. Characteristics and effectiveness of resultant antioxidant are also presented. The results obtained indicates that antioxidant made from hair keratin is safe and effective for rubber products from RVNRL. (author)

  6. Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and their major contributed antioxidant compounds

    OpenAIRE

    Mao, Shuqin; Wang, Kaidi; Lei, Yukun; Yao, Shuting; Lu, Baiyi; Huang, Weisu

    2017-01-01

    The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea were evaluated, and their major antioxidant compounds contributed to the total amount of synergy were determined. The antioxidant compounds in O. fragrans flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The synergistic antioxidant interactions between O. fragrans flowers with green tea and their antioxidant compounds were tested using the Prieto?s model after the simulated digestion. T...

  7. Antioxidant homoisoflavonoids from Polygonatum odoratum.

    Science.gov (United States)

    Zhou, Xiaoling; Yuping, Zhang; Zhao, Huading; Liang, Junsheng; Zhang, Yi; Shi, Shuyun

    2015-11-01

    Polygonatum odoratum is widely used as a traditional food supplement and herbal medicine with strong antioxidant activity. However, systematic investigation of its antioxidants was limited. Ethanol extract of P. odoratum was fractioned on macroporous absorptive resin (D101) column. A bioassay-guided purification of flavonoid-rich fraction (IC50 value at 74.1 ± 11.9 μg/mL for DPPH scavenging) was realised via high-speed counter-current chromatography (HSCCC) using petroleum ether-ethyl acetate-methanol-water (2:3:3:2, v/v/v/v) as the solvent system combination with Sephadex LH-20 column chromatography (CC) eluting with MeCN-MeOH (1:1, v/v). Three novel homoisoflavonoids (1-3), along with eight homoisoflavonoids (4-11), were isolated. Their structures were elucidated by interpretating various spectroscopic data. All the isolated homoisoflavonoids showed potent antioxidant activities, while compounds 1, 4, and 6 with dihydroxylated B-rings exhibited stronger antioxidant activities (IC50 values at 3.8 ± 0.5, 4.9 ± 0.3 and 3.9 ± 0.4 μg/mL) than ascorbic acid (IC50 value at 5.3 ± 0.6 μg/mL). Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Antioxidative activity of Geranium macrorrhizum

    NARCIS (Netherlands)

    Miliauskas, G.; Beek, van T.A.; Venskutonis, P.R.; Linssen, J.P.H.; Waard, de P.

    2004-01-01

    The composition of radical-scavenging compounds from Geranium macrorrhizum leaves was analyzed and the antioxidative activities of various extracts was determined. Seven compounds, namely gallic acid, ellagic acid, 4-galloyl quinic acid, the flavonoid quercetin and three of its glycosides,

  9. Antioxidant activity of Potentilla fruticosa

    NARCIS (Netherlands)

    Miliauskas, G.; Beek, van T.A.; Venskutonis, P.R.; Linssen, J.P.H.; Waard, de P.; Sudhölter, E.J.R.

    2004-01-01

    The molecular structures of the radical scavenging compounds present in extracts of Potentilla fruticosa blossoms were elucidated and the antioxidant activities of various extracts were determined. The activities of the different fractions were monitored by off-line and on-line RP-HPLC DPPH. and

  10. The state of antioxidant affairs

    NARCIS (Netherlands)

    Verhagen, H.; Buijsse, B.; Jansen, E.; Bueno de Mesquita, B.

    2006-01-01

    Oxidative stress is considered to be an adverse bodily event. Antioxidants are considered to be healthful because they may protect the body from oxidative damage. This simple paradigm is much more complicated in practice, however. Reactive oxygen species are a physiological necessity but too much of

  11. for antimicrobial and antioxidant activities

    African Journals Online (AJOL)

    Yomi

    2012-01-31

    Jan 31, 2012 ... An acetone extract of Loxostylis alata was separated into six fractions based on polarity by a solvent- solvent fractionation procedure and the different fractions were screened for antimicrobial and antioxidant activities. The number of antimicrobial compounds in the carbon tetrachloride (CCl4), chloroform ...

  12. Antioxidant capacity and physical exercise

    Directory of Open Access Journals (Sweden)

    A Marciniak

    2009-09-01

    Full Text Available The aim of this article is a presentation of current knowledge regarding the changes of plasma antioxidant capacity observed in response to physical exercise. Human body created the enzymatic and non-enzymatic systems, which play a protective role in the harmful impact of free radicals. Those two systems constitute what is known as the plasma total antioxidant capacity. The amount of reactive oxygen species (ROS and reactive nitrogen species (NOS in combination with oxidation processes increases in some tissues during physiological response to physical exercise. These changes are observed after single bout of exercise as well as after regular training. The response of human body to physical exercise can be analysed using various models of exercise test. Application of repeated type of exhaustion allows for characterizing the ability of human body to adjust to the increased energy loss and increased oxygen consumption. This article presents the characteristics of components of plasma antioxidant capacity, the mechanisms of free radicals production and their role in human body. It discusses also the currently used methods of detecting changes in total antioxidant capacity and its individual elements in response to single bout of exercise and regular training. It presents the review of literature about research performed in groups of both regularly training and low exercise activity individuals as well as in group of healthy subjects and patients with circulation diseases.

  13. Comparative antioxidant capacity, membrane stabilization ...

    African Journals Online (AJOL)

    Comparative antioxidant capacity, membrane stabilization, polyphenol composition and cytotoxicity of the leaf and stem of Cissus multistriata. ... standard anti-inflammatory drug (Indomethacin) used. The extracts are less toxic to the cell (Arthenia salina) with their LC/EC50 higher than that of standard potassium dichromate ...

  14. Antioxidant effects of green tea

    Science.gov (United States)

    FORESTER, SARAH C.; LAMBERT, JOSHUA D.

    2013-01-01

    Consumption of green tea (Camellia sinensis) may provide protection against chronic diseases, including cancer. Green tea polyphenols are believed to be responsible for this cancer preventive effect, and the antioxidant activity of the green tea polyphenols has been implicated as a potential mechanism. This hypothesis has been difficult to study in vivo due to metabolism of these compounds and poor understanding of the redox environment in vivo. Green tea polyphenols can be direct antioxidants by scavenging reactive oxygen species or chelating transition metals as has been demonstrated in vitro. Alternatively, they may act indirectly by up-regulating phase II antioxidant enzymes. Evidence of this latter effect has been observed in vivo, yet more work is required to determine under which conditions these mechanisms occur. Green tea polyphenols can also be potent pro-oxidants, both in vitro and in vivo, leading to the formation of hydrogen peroxide, the hydroxyl radical, and superoxide anion. The potential role of these pro-oxidant effects in the cancer preventive activity of green tea is not well understood. The evidence for not only the antioxidant, but also pro-oxidant, properties of green tea are discussed in the present review. PMID:21538850

  15. ANTIOXIDANT STATUS IN DIABETIC NEUROPATHY

    Directory of Open Access Journals (Sweden)

    Giriraja Vrushabaiah Kanakapura

    2017-09-01

    Full Text Available BACKGROUND Diabetic neuropathy, retinopathy and nephropathy are the chronic complications of diabetes mellitus. Neuropathy, retinopathy and nephropathy are microvascular complication of diabetes mellitus. Antioxidant status is reduced in DM-induced retinopathy and nephropathy. Present study is undertaken to evaluate the degree of oxidative stress in diabetic neuropathy patients. The aim of the study is to study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde and antienzyme status in type II DM patients with neuropathy and compared them with a controlled nondiabetic group. MATERIALS AND METHODS The study included 100 subjects from Sapthagiri Medical College, Bangalore, from January 1, 2015, to December 31, 2015, of age group 50 to 70 yrs. out of which 50 patients were non-insulin-dependent DM with neuropathy and rest 50 age and sex matched apparently healthy individuals (control group. Antioxidant status was assessed by measuring superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, Catalase and Reduced Glutathione (GSH. RESULTS It showed a significant increase p<0.001 in FBS, PPBS, TC, TG, LDL, VLDL, CAT, MDA, while HDL, GSH, GPX, GR and SOD were found to be decreased significantly (p 0.001. CONCLUSION MDA was significantly elevated in diabetic group, whereas antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly decreased, which might be helpful in risk assessment of various complications of DM. The data suggests that alteration in antioxidant status and MDA may help to predict the risk of diabetic neuropathy.

  16. Comparative antioxidant capacity, membrane stabilization ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-03

    Sep 3, 2008 ... In this present study, a comparative evaluation of the antioxidant capacities, phenol and polyphenol composition, membrane stabilization, and cytotoxicity to brine shrimps (Arthemia salina) of the leaf and stem extracts of Cissus multistriata were carried out. 2,2- Diphenyl-1-picryl hydrazyl (DPPH) radical.

  17. Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis

    Directory of Open Access Journals (Sweden)

    Cinthia Cristina Sousa de Menezes da Silveira

    2016-01-01

    Full Text Available Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP rich in triterpenoids, primarily lupeol and β-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control, EEYP (1, 3, 10, and 30 mg/kg, or diazepam, fluoxetine, and caffeine (positive controls 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product.

  18. Oxidative Stress and the Use of Antioxidants in Stroke

    Directory of Open Access Journals (Sweden)

    Rachel Shirley

    2014-07-01

    Full Text Available Transient or permanent interruption of cerebral blood flow by occlusion of a cerebral artery gives rise to an ischaemic stroke leading to irreversible damage or dysfunction to the cells within the affected tissue along with permanent or reversible neurological deficit. Extensive research has identified excitotoxicity, oxidative stress, inflammation and cell death as key contributory pathways underlying lesion progression. The cornerstone of treatment for acute ischaemic stroke remains reperfusion therapy with recombinant tissue plasminogen activator (rt-PA. The downstream sequelae of events resulting from spontaneous or pharmacological reperfusion lead to an imbalance in the production of harmful reactive oxygen species (ROS over endogenous anti-oxidant protection strategies. As such, anti-oxidant therapy has long been investigated as a means to reduce the extent of injury resulting from ischaemic stroke with varying degrees of success. Here we discuss the production and source of these ROS and the various strategies employed to modulate levels. These strategies broadly attempt to inhibit ROS production or increase scavenging or degradation of ROS. While early clinical studies have failed to translate success from bench to bedside, the combination of anti-oxidants with existing thrombolytics or novel neuroprotectants may represent an avenue worthy of clinical investigation. Clearly, there is a pressing need to identify new therapeutic alternatives for the vast majority of patients who are not eligible to receive rt-PA for this debilitating and devastating disease.

  19. In vitro antioxidant studies in leaves of Annona species.

    Science.gov (United States)

    Baskar, R; Rajeswari, V; Kumar, T Sathish

    2007-05-01

    Antioxidant potential of leaves of three different species of Annona was studied by using different in vitro models eg., 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothizoline-6-sulphonate) (ABTS), nitric oxide, superoxide, hydroxy radical and lipid peroxidation. The ethanolic extract of A. muricata at 500 microg/ml showed maximum scavenging activity (90.05%) of ABTS radical cation followed by the scavenging of hydroxyl radical (85.88%) and nitric oxide (72.60%) at the same concentration. However, the extract showed only moderate lipid peroxidation inhibition activity. In contrast, the extract of A. reticulata showed better activity in quenching DPPH (89.37%) and superoxide radical (80.88%) respectively. A.squamosa extract exhibited least inhibition in all in vitro antioxidant models excepting hydroxyl radical (79.79%). These findings suggest that the extracts of A. muricata possess potent in vitro antioxidant activity as compared to leaves of A. squamosa and A. reticulata suggesting its role as an effective free radical scavenger, augmenting its therapeutic

  20. Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis

    Science.gov (United States)

    da Silveira, Cinthia Cristina Sousa de Menezes; Fernandes, Luanna Melo Pereira; Silva, Mallone Lopes; Luz, Diandra Araújo; Gomes, Antônio Rafael Quadros; Machado, Christiane Schineider; de Lira, Tatiana Onofre; Ferreira, Antonio Gilberto

    2016-01-01

    Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP) rich in triterpenoids, primarily lupeol and β-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control), EEYP (1, 3, 10, and 30 mg/kg), or diazepam, fluoxetine, and caffeine (positive controls) 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product. PMID:27822336

  1. Antioxidant properties of melatonin--an emerging mystery.

    Science.gov (United States)

    Beyer, C E; Steketee, J D; Saphier, D

    1998-11-15

    Over three centuries ago, the French philosopher René Descartes described the pineal gland as "the seat of the soul." However, it was not until the late 1950s that the chemical identity and biosynthesis of melatonin, the principal hormone secreted by the pineal body, were revealed. Melatonin, named from the Greek melanos, meaning black, and tonos, meaning color, is a biogenic amine with structural similarities to serotonin. The mechanisms mediating the synthesis of melatonin are transcriptionally regulated by the photoperiodic environment. Once synthesized, the neurohormone is a biologic modulator of mood, sleep, sexual behavior, reproductive alterations, immunologic function, and circadian rhythms. Moreover, melatonin exerts its regulatory roles through high-affinity, pertussis toxin-sensitive, G-protein (or guanine nucleotide binding protein) coupled receptors that reside primarily in the eye, kidney, gastrointestinal tract, blood vessels, and brain. Additional evidence also indicates a role for melatonin in aging and age-related diseases, probably related to its efficient free radical scavenger (or antioxidant) activity. The potential clinical benefit of melatonin as an antioxidant is remarkable, suggesting that it may be of use in the treatment of many pathophysiological disease states including various cancers, hypertension, pulmonary diseases, and a variety of neurodegenerative diseases such as Alzheimer's disease. This review summarizes the biosynthesis of melatonin and its many endocrine and physiological functions, including its therapeutic potential in human disease states. Emphasis is placed on the recent speculations indicating that this pineal hormone serves as an endogenous antioxidant agent with proficient free radical scavenging activity.

  2. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    polymerized in a controlled manner with carrier monomers of historically proven biocompatible polymers. The carrier polymers, the loading of ribavirin as well as the size of the polymer were varied systematically with the aid of an automated synthesis platform. These polymers were tested in a cellular assay...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein......The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...

  3. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    to the harsh and selective gastrointestinal system, and development has lacked far behind injection therapy. Peptide acylation is a powerful tool to alter the pharmacokinetics, biophysical properties and chemical stability of injectable peptide drugs, primarily used to prolong blood circulation....... This work aims to characterize acylated analogues of two therapeutic peptides by systematically increasing acyl chain length in order to elucidate its influence on membrane interaction and intestinal cell translocation in vitro. The studied peptides are the 33 amino acid Glucagon-like peptide-2 (GLP-2...... peptides can increase in vitro intestinal permeability, modestly for GLP-2 and drastically for sCT, and might benefit oral delivery. GLP-2 results provide a well-founded predictive power for future peptide analogues, whereas sCT results hold great promise for future analogues, albeit with a larger...

  4. Therapeutic and diagnostic nanomaterials

    CERN Document Server

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  5. [Therapeutic education didactic techniques].

    Science.gov (United States)

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  6. Metabolic characterization and antioxidant activity in sweet cherry (Prunus avium L.) Campania accessions: Metabolic characterization of sweet cherry accessions.

    Science.gov (United States)

    Mirto, Antonio; Iannuzzi, Federica; Carillo, Petronia; Ciarmiello, Loredana F; Woodrow, Pasqualina; Fuggi, Amodio

    2018-02-01

    The failure of the antioxidant scavenging system in advanced ripening stages, causing oxidative stress, is one of the most important factor of fruit decay. Production of rich antioxidant fruit could represent a way to delay fruit senescence and preserve its characteristics. We investigated the antioxidant metabolites (ascorbate, glutathione, tocopherols, and polyphenols) and enzymes (ascorbic peroxidases, peroxidases and polyphenol oxidases) involved in the antioxidant response in forty-three accessions of sweet cherry fruits from Campania region. Our results highlight accessions with high antioxidant metabolites contents but low enzymatic activities. These represent important factors in both pre- and post-harvest on the qualitative and nutritional characteristics of sweet cherry. Observed differences are probably due to endogenous characteristics making these accessions particularly interesting for breeding programs aimed to improve fruit quality and shelf-life and for addressing the cultivation of a specific characterized cultivar based on the intended use, fresh consumption or processed products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Treating troubled families: therapeutic scenario in India.

    Science.gov (United States)

    Thomas, Bino

    2012-04-01

    India, a country of diverse cultures, languages, life styles, and ethnicities, is becoming a land of economic change, political stability, technological advancement, and changing traditional structures of relationships as well as health consciousness. Being known for its ancient traditions, rituals, religious orientation, spiritual outlook and folk beliefs, Indian families attempt to continue certain healthy and traditional elements such as warmth, strong bond, hierarchy, extended support, cultural orientation, shared values and time, tolerance, respect for the aged and inculcation of religious teachings and traditions in families. These factors, or practices, in fact have strong therapeutic value in supplementing the growth and development of individuals in the family system in spite of its transitional position. This paper deals with the review of family-based mental health services and focuses on the changing trends of those practices in India and the advancement of Indian families in their engaging ability with mentally ill members as well as with the treating team.

  8. Recent Advances and Uses of Grape Flavonoids as Nutraceuticals

    Science.gov (United States)

    Georgiev, Vasil; Ananga, Anthony; Tsolova, Violeta

    2014-01-01

    Grape is one of the oldest fruit crops domesticated by humans. The numerous uses of grape in making wine, beverages, jelly, and other products, has made it one of the most economically important plants worldwide. The complex phytochemistry of the berry is characterized by a wide variety of compounds, most of which have been demonstrated to have therapeutic or health promoting properties. Among them, flavonoids are the most abundant and widely studied, and have enjoyed greater attention among grape researchers in the last century. Recent studies have shown that the beneficial health effects promoted by consumption of grape and grape products are attributed to the unique mix of polyphenolic compounds. As the largest group of grape polyphenols, flavonoids are the main candidates considered to have biological properties, including but not limited to antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, cardioprotective, neuroprotective, and hepatoprotective activities. Here, we discuss the recent scientific advances supporting the beneficial health qualities of grape and grape-derived products, mechanisms of their biological activity, bioavailability, and their uses as nutraceuticals. The advantages of modern plant cell based biotechnology as an alternative method for production of grape nutraceuticals and improvement of their health qualities are also discussed. PMID:24451310

  9. Recent Advances and Uses of Grape Flavonoids as Nutraceuticals

    Directory of Open Access Journals (Sweden)

    Vasil Georgiev

    2014-01-01

    Full Text Available Grape is one of the oldest fruit crops domesticated by humans. The numerous uses of grape in making wine, beverages, jelly, and other products, has made it one of the most economically important plants worldwide. The complex phytochemistry of the berry is characterized by a wide variety of compounds, most of which have been demonstrated to have therapeutic or health promoting properties. Among them, flavonoids are the most abundant and widely studied, and have enjoyed greater attention among grape researchers in the last century. Recent studies have shown that the beneficial health effects promoted by consumption of grape and grape products are attributed to the unique mix of polyphenolic compounds. As the largest group of grape polyphenols, flavonoids are the main candidates considered to have biological properties, including but not limited to antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, cardioprotective, neuroprotective, and hepatoprotective activities. Here, we discuss the recent scientific advances supporting the beneficial health qualities of grape and grape-derived products, mechanisms of their biological activity, bioavailability, and their uses as nutraceuticals. The advantages of modern plant cell based biotechnology as an alternative method for production of grape nutraceuticals and improvement of their health qualities are also discussed.

  10. Biomaterials and therapeutic applications

    Science.gov (United States)

    Ferraro, Angelo

    2016-03-01

    A number of organic and inorganic, synthetic or natural derived materials have been classified as not harmful for the human body and are appropriate for medical applications. These materials are usually named biomaterials since they are suitable for introduction into living human tissues of prosthesis, as well as for drug delivery, diagnosis, therapies, tissue regeneration and many other clinical applications. Recently, nanomaterials and bioabsorbable polymers have greatly enlarged the fields of application of biomaterials attracting much more the attention of the biomedical community. In this review paper I am going to discuss the most recent advances in the use of magnetic nanoparticles and biodegradable materials as new biomedical tools.

  11. Melatonin: Action as antioxidant and potential applications in human disease and aging

    International Nuclear Information System (INIS)

    Bonnefont-Rousselot, Dominique; Collin, Fabrice

    2010-01-01

    This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

  12. Antioxidant status in vegetarians versus omnivores.

    Science.gov (United States)

    Rauma, A L; Mykkänen, H

    2000-02-01

    Every day, vegetarians consume many carbohydrate-rich plant foods such as fruits and vegetables, cereals, pulses, and nuts. As a consequence, their diet contains more antioxidant vitamins (vitamin C, vitamin E, and beta-carotene) and copper than that of omnivores. Intake of zinc is generally comparable to that by omnivores. However, the bioavailability of zinc in vegetarian diets is generally lower than that of omnivores. Dietary intake of selenium is variable in both groups and depends on the selenium content of the soil. Measurements of antioxidant body levels in vegetarians show that a vegetarian diet maintains higher antioxidant vitamin status (vitamin C, vitamin E, beta-carotene) but variable antioxidant trace element status as compared with an omnivorous diet. To evaluate the antioxidative potential of a vegetarian diet versus an omnivorous diet, more studies are needed in which the total antioxidant capacity is determined rather than the status of a single antioxidant nutrient.

  13. Quercetin: A wonder bioflvonoid with therapeutic potential in disease management

    Directory of Open Access Journals (Sweden)

    Alka Gupta

    2016-03-01

    Full Text Available In the last decade, considerable efforts have been made to develop health promising nutritional supplements. Quercetin is a plant-derived bioflavonoid which is recently gaining scientific interest for its antioxidant free radical scavenging effects and anti-inflammatory properties. This wonder flavanol exhibits therapeutic potential in various ailments like cancer, coronary artery, asthma and alzheimer (neurodegeneration diseases. Additional clinical uses include treatment of inflammatory conditions like gout, pancreatitis and prostatitis. It has been extensively studied for its gastroprotective effects, anti-obesity action, immune booster, reducing risk of cataract and reduction of diabetic complications. The present review briefly discusses about biological activity, mechanism of action and therapeutic potential of quercetin in prevention and mitigation of diseases.

  14. Therapeutic Applications of Rose Hips from Different Rosa Species

    Directory of Open Access Journals (Sweden)

    Inés Mármol

    2017-05-01

    Full Text Available Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.

  15. Therapeutic Applications of Rose Hips from Different Rosa Species.

    Science.gov (United States)

    Mármol, Inés; Sánchez-de-Diego, Cristina; Jiménez-Moreno, Nerea; Ancín-Azpilicueta, Carmen; Rodríguez-Yoldi, María Jesús

    2017-05-25

    Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.

  16. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    Science.gov (United States)

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.

  17. On the Toxicity of Therapeutically Used Nanoparticles: An Overview

    Directory of Open Access Journals (Sweden)

    A. El-Ansary

    2009-01-01

    Full Text Available Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. The rapidly developing field of nanotechnology will result in new sources of this exposure, through inhalation, ingestion, and injection. Although nanomaterials are currently being widely used in modern technology, there is a serious lack of information concerning the human health and environmental implications of manufactured nanomaterials. Since these are relatively new particles, it is necessary to investigate their toxicological behavior. The objective of this review was to trace the cellular response to nanosized particle exposure. Therapeutic application of selected nanoparticles together with their range of toxic doses was also reviewed. Effect of therapeutically used nanoparticles on cell membrane, mitochondrial function, prooxidant/antioxidant status, enzyme leakage, DNA, and other biochemical endpoints was elucidated. This paper highlights the need for caution during the use and disposal of such manufactured nanomaterials to prevent unintended environmental impacts.

  18. Advancements in meat packaging.

    Science.gov (United States)

    McMillin, Kenneth W

    2017-10-01

    Packaging of meat provides the same or similar benefits for raw chilled and processed meats as other types of food packaging. Although air-permeable packaging is most prevalent for raw chilled red meat, vacuum and modified atmosphere packaging offer longer shelf life. The major advancements in meat packaging have been in the widely used plastic polymers while biobased materials and their integration into composite packaging are receiving much attention for functionality and sustainability. At this time, active and intelligent packaging are not widely used for antioxidant, antimicrobial, and other functions to stabilize and enhance meat properties although many options are being developed and investigated. The advances being made in nanotechnology will be incorporated into food packaging and presumably into meat packaging when appropriate and useful. Intelligent packaging using sensors for transmission of desired information and prompting of subsequent changes in packaging materials, environments or the products to maintain safety and quality are still in developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Plant derived antioxidants and antifibrotic drugs: past, present and future

    Directory of Open Access Journals (Sweden)

    Devaraj Ezhilarasan

    2014-09-01

    Full Text Available Hepatic fibrosis occurs as a wound-healing process after several forms of chronic hepatic injury. Activation and proliferation of hepatic stellate cells play pivotal role in the pathogenesis of hepatic fibrosis. Many researchers, from the therapeutic perspective, have focused their attention on searching for novel agents with inhibitory effects on hepatic stellate cells proliferation and activation to prevent hepatic fibrogenesis and a number of plant derived antioxidants have been tested as anti-fibrogenic agents, they generally suppress proliferation and collagen synthesis. Plants remain an imperative source of novel drugs, novel drug leads and new chemical entities. The plant based drug discovery resulted primarily in the development of antioxidant, anti-cancer and other anti-infectious agents and continues to contribute to the new leads in clinical trials. This review summarizes some of those most important plant derived anti-fibrotic drugs and their beneficial effects on experimentally induced hepatic fibrosis in vitro and in vivo. The plant derived antioxidant compounds described herein are curcumin, silymarin, silibinin, baicalein, resveratrol, salvianolic acids, tetrandine, quercetin and berberine. Studies from ours and as demonstrated by pervious workers much information has been accumulated over the past two decades through in vivo and in vitro. In light of those studies, it has been confirmed that plants derived antioxidants, particularly flavanoids, show a significant influence to block hepatic fibrosis regardless of any etiology. This review outlines recent progress in the use of plant derived drugs against experimentally induced liver fibrosis by in vitro and in vivo studies and summarizes the possible mechanisms anti-fibrotic effects of these compounds.

  20. Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants

    Science.gov (United States)

    Hampson, A. J.; Grimaldi, M.; Axelrod, J.; Wink, D.

    1998-01-01

    The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (−)Δ9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-d-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-d-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or α-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia. PMID:9653176

  1. Therapeutic strategies in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Leonello eFuso

    2011-04-01

    Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

  2. Therapeutic Strategies in Pulmonary Hypertension

    Science.gov (United States)

    Fuso, Leonello; Baldi, Fabiana; Perna, Alessandra Di

    2011-01-01

    Pulmonary hypertension (PH) is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH) whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an “ideal” therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators. PMID:21687513

  3. Antioxidant Capacities of Fractions of Bamboo Shaving Extract and Their Antioxidant Components.

    Science.gov (United States)

    Gong, Jinyan; Huang, Jun; Xiao, Gongnian; Chen, Feng; Lee, Bolim; Ge, Qing; You, Yuru; Liu, Shiwang; Zhang, Ying

    2016-07-30

    This research was conducted for evaluation of antioxidant activities of four fractions from bamboo shavings extract (BSE) and their antioxidant components. The antioxidant capacities of BSE and four fractions on ABTS, DPPH, FRAP and total antioxidant capacity assays exhibited the following descending order: DF > n-butanol fraction (BF) > BSE ≈ ethyl acetate fraction (AF) > water fraction (WF). Among the identified phenolic compounds, caffeic acid exhibited the highest antioxidant capacities on DPPH, FRAP and total antioxidant capacity assays. An extremely significant positive correlation between the antioxidant activities with the contents of total flavonoids, total phenolic acids, or total phenolics was observed in this study. The result indicated that the bamboo shaving extract and its solvent fractions could act as natural antioxidants in light of their potent antioxidant activities.

  4. Pharmacological actions and therapeutic uses of cannabis and cannabinoids.

    Science.gov (United States)

    Kumar, R N; Chambers, W A; Pertwee, R G

    2001-11-01

    This review highlights the pharmacology, pharmacokinetics, pharmacological actions, therapeutic uses and adverse effects of cannabinoids. The effect of cannabinoids on anaesthesia is mentioned briefly. Important advances have taken place in cannabinoid research over the last few years and have led to the discovery of novel ligands. The possible clinical applications of these ligands and the direction of future research are discussed.

  5. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  6. Critical reflexivity in client-centred therapeutic relationships.

    Science.gov (United States)

    McCorquodale, Lisa; Kinsella, Elizabeth Anne

    2015-07-01

    This paper explores how a particular form of reflection--critical reflexivity--can support clinicians in developing a more nuanced understanding of therapeutic relationships, and work to advance the goal of client-centred practice. A critical autobiographical narrative was written, and critical reflexivity adopted, as methods to critically examine the therapeutic relationship. Critically reflexive stories have the potential to advance client-centred therapeutic relationships by inspiring the (re-)consideration of practices, and by interrogating interpretive systems. Understandings and practices that potentially limit the extent to which therapeutic relationships are client centred include (i) Dichotomous thinking, (ii) Objectification, (iii) The economic imperative, and (iv) Knowledge generation. The critical autobiographical account points to ways in which critical reflexivity on the therapeutic relationship has the potential to foster critical questioning, interrogate interpretive systems, attune to subjectivities, contribute to practice-based knowledge, resist violation, foster compassionate practice, and develop new understandings of relevance to client-centred practice. This critical examination of the therapeutic relationship supports occupational therapists in more fully realizing the profession's core value of client-centred practice.

  7. Oxidative Stress in Human Atherothrombosis: Sources, Markers and Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Jose Luis Martin-Ventura

    2017-11-01

    Full Text Available Atherothrombosis remains one of the main causes of morbidity and mortality worldwide. The underlying pathology is a chronic pathological vascular remodeling of the arterial wall involving several pathways, including oxidative stress. Cellular and animal studies have provided compelling evidence of the direct role of oxidative stress in atherothrombosis, but such a relationship is not clearly established in humans and, to date, clinical trials on the possible beneficial effects of antioxidant therapy have provided equivocal results. Nicotinamide adenine dinucleotide phosphate (NADPH oxidase is one of the main sources of reactive oxygen species (ROS in human atherothrombosis. Moreover, leukocyte-derived myeloperoxidase (MPO and red blood cell-derived iron could be involved in the oxidative modification of lipids/lipoproteins (LDL/HDL in the arterial wall. Interestingly, oxidized lipoproteins, and antioxidants, have been analyzed as potential markers of oxidative stress in the plasma of patients with atherothrombosis. In this review, we will revise sources of ROS, focusing on NADPH oxidase, but also on MPO and iron. We will also discuss the impact of these oxidative systems on LDL and HDL, as well as the value of these modified lipoproteins as circulating markers of oxidative stress in atherothrombosis. We will finish by reviewing some antioxidant systems and compounds as therapeutic strategies to prevent pathological vascular remodeling.

  8. Therapeutic vaccines for leishmaniasis.

    Science.gov (United States)

    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.

  9. Camel Milk as a Potential Therapy as an Antioxidant in Autism Spectrum Disorder (ASD

    Directory of Open Access Journals (Sweden)

    Laila Y. AL-Ayadhi

    2013-01-01

    Full Text Available Extensive studies have demonstrated that oxidative stress plays a vital role in the pathology of several neurological diseases, including autism spectrum disorder (ASD; those studies proposed that GSH and antioxidant enzymes have a pathophysiological role in autism. Furthermore, camel milk has emerged to have potential therapeutic effects in autism. The aim of the current study was to evaluate the effect of camel milk consumption on oxidative stress biomarkers in autistic children, by measuring the plasma levels of glutathione, superoxide dismutase, and myeloperoxidase before and 2 weeks after camel milk consumption, using the ELISA technique. All measured parameters exhibited significant increase after camel milk consumption (. These findings suggest that camel milk could play an important role in decreasing oxidative stress by alteration of antioxidant enzymes and nonenzymatic antioxidant molecules levels, as well as the improvement of autistic behaviour as demonstrated by the improved Childhood Autism Rating Scale (CARS.

  10. Advance Directives

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma ... about advance directives. Two well-known ones are: Aging With Dignity Aging with Dignity is a national ...

  11. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    Whittaker, Peter A.

    2005-01-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  12. Mining the Genome for Therapeutic Targets.

    Science.gov (United States)

    Florez, Jose C

    2017-07-01

    Current pharmacological options for type 2 diabetes do not cure the disease. Despite the availability of multiple drug classes that modulate glycemia effectively and minimize long-term complications, these agents do not reverse pathogenesis, and in practice they are not selected to correct the molecular profile specific to the patient. Pharmaceutical companies find drug development programs increasingly costly and burdensome, and many promising compounds fail before launch to market. Human genetics can help advance the therapeutic enterprise. Genomic discovery that is agnostic to preexisting knowledge has uncovered dozens of loci that influence glycemic dysregulation. Physiological investigation has begun to define disease subtypes, clarifying heterogeneity and suggesting molecular pathways for intervention. Convincing genetic associations have paved the way for the identification of effector transcripts that underlie the phenotype, and genetic or experimental proof of gain or loss of function in select cases has clarified the direction of effect to guide therapeutic development. Genetic studies can also examine off-target effects and furnish causal inference. As this information is curated and made widely available to all stakeholders, it is hoped that it will enhance therapeutic development pipelines by accelerating efficiency, maximizing cost-effectiveness, and raising ultimate success rates. © 2017 by the American Diabetes Association.

  13. Genesis and development of DPPH method of antioxidant assay.

    Science.gov (United States)

    Kedare, Sagar B; Singh, R P

    2011-08-01

    α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging method offers the first approach for evaluating the antioxidant potential of a compound, an extract or other biological sources. This is the simplest method, wherein the prospective compound or extract is mixed with DPPH solution and absorbance is recorded after a defined period. However, with the advancement and sophistication in instrumental techniques, the method has undergone various modifications to suit the requirements, even though the basic approach remains same in all of them. This article presents a critical review on various developments to the DPPH method.

  14. Antioxidant therapy: myth or reality?

    International Nuclear Information System (INIS)

    Nunez-Selles, Alberto J.

    2005-01-01

    New terms such as oxidative stress, antioxidant products or pro-oxidant risks are becoming familiar and an increasing number of international scientific conferences and the publication of thousands of scientific articles is an indication of the growing interest that the subject awakens. The most publicized example is perhaps the French paradox, based on the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis attributed to the regular consumption, by the French, of red wine and/or grape juice. Flavonoids, and other phenolic substances contained in red wine, are assigned with antioxidant properties, which lower the oxidation of low density lipoproteins and consequently, the risk of atherogenic diseases. Other examples are the aging process and its correlation with an increase of free radicals, and the correlation between the initiation and promotion of cancer and tissue injury by free radicals, which has induced the intake of antioxidant products as chemical factors that prevent the onset of the disease. Currently, the incidence of oxidative stress on the onset and evolution of more than 100 diseases is claimed by several researchers. All these are 'realities', which on the other hand, are lacking of more clinical evidence, are considered by both physicians and health regulatory bodies, either as 'myths' or of 'secondary' importance. In the attempts to destroy those myths, results of chemical, pre-clinical, and clinical works with a crude extract of mango (Mangifera indica L.) stem bark, which has been developed in Cuba, are reviewed, with a strong experimental evidence of its antioxidant, anti-inflammatory and immunomodulatory properties. (author)

  15. Antioxidant properties of Brassica vegetables

    OpenAIRE

    Soengas Fernández, María del Pilar; Sotelo Pérez, Tamara; Velasco Pazos, Pablo; Cartea González, María Elena

    2011-01-01

    Brassica vegetables include some economically interesting crops such as cabbage, broccoli, cauliflower, Brussels sprouts, kale and turnip, which are consumed all over the world. A high intake of Brassica vegetables reduces the risk of age-related chronic illness such as cardiovascular health and other degenerative diseases and reduces the risk of several types of cancer, thanks in part to the antioxidant properties of different compounds. Compared to other vegetables, Brassica vegetables have...

  16. Antioxidant therapy: myth or reality?

    Energy Technology Data Exchange (ETDEWEB)

    Nunez-Selles, Alberto J. [Center of Pharmaceutical Chemistry, Havana (Cuba)]. E-mail: alberto@cqf.co.cu

    2005-07-15

    New terms such as oxidative stress, antioxidant products or pro-oxidant risks are becoming familiar and an increasing number of international scientific conferences and the publication of thousands of scientific articles is an indication of the growing interest that the subject awakens. The most publicized example is perhaps the French paradox, based on the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis attributed to the regular consumption, by the French, of red wine and/or grape juice. Flavonoids, and other phenolic substances contained in red wine, are assigned with antioxidant properties, which lower the oxidation of low density lipoproteins and consequently, the risk of atherogenic diseases. Other examples are the aging process and its correlation with an increase of free radicals, and the correlation between the initiation and promotion of cancer and tissue injury by free radicals, which has induced the intake of antioxidant products as chemical factors that prevent the onset of the disease. Currently, the incidence of oxidative stress on the onset and evolution of more than 100 diseases is claimed by several researchers. All these are 'realities', which on the other hand, are lacking of more clinical evidence, are considered by both physicians and health regulatory bodies, either as 'myths' or of 'secondary' importance. In the attempts to destroy those myths, results of chemical, pre-clinical, and clinical works with a crude extract of mango (Mangifera indica L.) stem bark, which has been developed in Cuba, are reviewed, with a strong experimental evidence of its antioxidant, anti-inflammatory and immunomodulatory properties. (author)

  17. A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense

    Directory of Open Access Journals (Sweden)

    Udayakumar Karunakaran

    2013-04-01

    Full Text Available A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially β-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic β-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and β-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect β-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with β-cell failure.

  18. Colorectal cancer: diagnostic and therapeutic strategies

    International Nuclear Information System (INIS)

    Vaillant, J.C.

    1996-01-01

    Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)

  19. Global antioxidant response of meat.

    Science.gov (United States)

    Carrillo, Celia; Barrio, Ángela; Del Mar Cavia, María; Alonso-Torre, Sara

    2017-06-01

    The global antioxidant response (GAR) method uses an enzymatic digestion to release antioxidants from foods. Owing to the importance of digestion for protein breakdown and subsequent release of bioactive compounds, the aim of the present study was to compare the GAR method for meat with the existing methodologies: the extraction-based method and QUENCHER. Seven fresh meats were analyzed using ABTS and FRAP assays. Our results indicated that the GAR of meat was higher than the total antioxidant capacity (TAC) assessed with the traditional extraction-based method. When evaluated with GAR, the thermal treatment led to an increase in the TAC of the soluble fraction, contrasting with a decreased TAC after cooking measured using the extraction-based method. The effect of thermal treatment on the TAC assessed by the QUENCHER method seemed to be dependent on the assay applied, since results from ABTS differed from FRAP. Our results allow us to hypothesize that the activation of latent bioactive peptides along the gastrointestinal tract should be taken into consideration when evaluating the TAC of meat. Therefore, we conclude that the GAR method may be more appropriate for assessing the TAC of meat than the existing, most commonly used methods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  20. Systemic antioxidants and skin health.

    Science.gov (United States)

    Nguyen, Gloria; Torres, Abel

    2012-09-01

    Most dermatologists agree that antioxidants help fight free radical damage and can help maintain healthy skin. They do so by affecting intracellular signaling pathways involved in skin damage and protecting against photodamage, as well as preventing wrinkles and inflammation. In today's modern world of the rising nutraceutical industry, many people, in addition to applying topical skin care products, turn to supplementation of the nutrients missing in their diets by taking multivitamins or isolated, man-made nutraceuticals, in what is known as the Inside-Out approach to skin care. However, ingestion of large quantities of isolated, fragmented nutrients can be harmful and is a poor representation of the kind of nutrition that can be obtained from whole food sources. In this comprehensive review, it was found that few studies on oral antioxidants benefiting the skin have been done using whole foods, and that the vast majority of current research is focused on the study of compounds in isolation. However, the public stands to benefit greatly if more research were to be devoted toward the impact that physiologic doses of antioxidants (obtained from fruits, vegetables, and whole grains) can have on skin health, and on health in general.

  1. AdvancED Flex 4

    CERN Document Server

    Tiwari, Shashank; Schulze, Charlie

    2010-01-01

    AdvancED Flex 4 makes advanced Flex 4 concepts and techniques easy. Ajax, RIA, Web 2.0, mashups, mobile applications, the most sophisticated web tools, and the coolest interactive web applications are all covered with practical, visually oriented recipes. * Completely updated for the new tools in Flex 4* Demonstrates how to use Flex 4 to create robust and scalable enterprise-grade Rich Internet Applications.* Teaches you to build high-performance web applications with interactivity that really engages your users.* What you'll learn Practiced beginners and intermediate users of Flex, especially

  2. Nanoparticle-Based Delivery of RNAi Therapeutics: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    John C. Burnett

    2013-01-01

    Full Text Available RNA interference (RNAi is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. Although RNAi therapeutics have recently progressed through the pipeline toward clinical trials, the application of these as ideal, clinical therapeutics requires the development of safe and effective delivery systems. Inspired by the immense progress with nanotechnology in drug delivery, efforts have been dedicated to the development of nanoparticle-based RNAi delivery systems. For example, a precisely engineered, multifunctional nanocarrier with combined passive and active targeting capabilities may address the delivery challenges for the widespread use of RNAi as a therapy. Therefore, in this review, we introduce the major hurdles in achieving efficient RNAi delivery and discuss the current advances in applying nanotechnology-based delivery systems to overcome the delivery hurdles of RNAi therapeutics. In particular, some representative examples of nanoparticle-based delivery formulations for targeted RNAi therapeutics are highlighted.

  3. [Mutative processes of structural skills in therapeutic-pedagogic contexts].

    Science.gov (United States)

    Traxl, Bernd

    2011-01-01

    Therapeutic-pedagogic processes are above all orientated on cognitive, perceptive, mnestic or motoric deficits, particularly with children and adolescents. Thereby psychodynamic dimensions and structural skills are neglected. I want to focus on this underrepresented domain and place it in the centre of the therapeutic-pedagogic interest. The OPD-2 is currently the most sophisticated raster of psychic structure and so I use it for my theoretic frame of reference. The specific criteria are described to work out the concrete support in the context of therapeutic-pedagogic. On the basis of a short case study, I illustrate the developmental and modification possibilities to corroborate my belief, that therapeutic-pedagogic relations advance mutative process in the range of structural skills.

  4. Therapeutic implications of melatonin in cerebral edema.

    Science.gov (United States)

    Rathnasamy, Gurugirijha; Ling, Eng-Ang; Kaur, Charanjit

    2014-12-01

    Cerebral edema/brain edema refers to the accumulation of fluid in the brain and is one of the fatal conditions that require immediate medical attention. Cerebral edema develops as a consequence of cerebral trauma, cerebral infarction, hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based on the causative factors cerebral edema is differentiated into cytotoxic cerebral edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema. Treatment of cerebral edema depends on timely diagnosis and medical assistance. Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D-aspartate receptor antagonists and trometamol are used in clinical practice. Although the above mentioned treatment approaches are being used, owing to the complexity of the mechanisms involved in cerebral edema, a single therapeutic strategy which could ameliorate cerebral edema is yet to be identified. However, recent experimental studies have suggested that melatonin, a neurohormone produced by the pineal gland, could be an effective alternative for treating cerebral edema. In animal models of stroke, melatonin was not only shown to reduce cerebral edema but also preserved the blood brain barrier. Melatonin's beneficial effects were attributed to its properties, such as being a potent anti-oxidant, and its ability to cross the blood brain barrier within minutes after its administration. This review summarizes the beneficial effects of melatonin when used for treating cerebral edema.

  5. Trichilia catigua: therapeutic and cosmetic values

    Directory of Open Access Journals (Sweden)

    Renata Longhini

    Full Text Available ABSTRACT Medicinal plants play an important role in human health care. It is estimated that about 25–30% of all drugs are evaluated as therapeutic agents derived from natural products. Research in the pharmaceutical industry has demonstrated that for complex diseases, natural products still represent a valuable source for the production of new chemical compounds, since they possess privileged structures. Among Brazilian biodiversity, "catuaba" is popularly used as a tonic to treat fatigue, stress, impotence, memory deficits, and digestive disorders. Studies show antibacterial, trypanocidal, antioxidant, antiarrhythmic, antidepressant, improvement of memory, anti-inflammatory and antinociceptive activities, as well as phytocosmetic activity in cellulite treatment and in anti-ageing. The Brazilian plants known and used as catuaba are represented by more than twenty different species; however, the plant most commonly found in Brazil as "catuaba" is the species Trichilia catigua A. Juss., Meliaceae. Thus, the aim of this paper is to present a review of T. catigua, with emphasis on biological activities, chemical and analytical development and formulations in order to provide a broader and deeper insight, seeking a herbal medicine and/or phytocosmetic as well as future prospects for commercial exploitation and directions for future studies.

  6. Purinergic Signalling: Therapeutic Developments.

    Science.gov (United States)

    Burnstock, Geoffrey

    2017-01-01

    Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A 2A receptor antagonists are promising for the treatment of Parkinson's disease. Clopidogrel, a P2Y 12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y 12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y 2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  7. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  8. Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

    Science.gov (United States)

    Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

    2016-12-01

    Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

  9. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  10. Towards further understanding on the antioxidative activities of Prunus persica fruit: A comparative study with four different fractions

    Science.gov (United States)

    Dhingra, Naveen; Sharma, Rajesh; Kar, Anand

    2014-11-01

    In the present study we have evaluated the antioxidant activities of different fractions (hexane, ethyl acetate, n-butanol and aqueous fractions) of Prunus persica fruit. For extraction simple warring blender method was employed and total phenolic and flavonoid contents were correlated with different antioxidant activities (total antioxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2 scavenging, superoxide radical scavenging, iron chelating and their reducing power properties). Different in vitro antioxidant studies showed that ethyl acetate and n-butanol fractions had the maximum activities that were well correlated with total phenolic and flavonoid contents. Maximum yield (25.14 ± 2.2%) was obtained in its aqueous fraction. Both ethyl acetate and n-butanol fractions showed significant inhibitory effects on different antioxidant activities. A significantly high correlation coefficient existed between total antioxidant activities and with total phenolic as well as total flavonoid contents. It appears that ethyl acetate and n-butanol fractions of P. persica may serve as new potential sources of natural antioxidants and could be of therapeutic use in treating several diseases.

  11. Therapeutic robotics for children with disabilities: a case study.

    Science.gov (United States)

    Drane, James; Safos, Charlotte; Lathan, Corinna E

    2009-01-01

    The advancement of technology is having a profound effect on enhancing the lives of children with disabilities. As advances in biomedical technology allow research breakthroughs to continue at a steady pace, more and more is being discovered about the nature of different disorders in children. At the same time, partly due to the continuing rapid rate of advancement (and societal acceptance) of robotics technology, researchers, educators, and therapists are exploring the idea that robots might be used as an effective therapeutic and educational tool. Over the past nine years, AnthroTronix has collaborated extensively with therapists, educators, researchers, parents, and children to uncover the therapeutic and educational benefits of including robotics as part of rehabilitation curriculum for children. As a central part of this effort, the company has worked with its colleagues to develop and refine the CosmoBot system, an interactive robotic toolkit designed to enhance therapy, education, and play for children with disabilities.

  12. Nanoencapsulation strategies for the delivery of novel bifunctional antioxidant/σ1 selective ligands.

    Science.gov (United States)

    Carbone, Claudia; Arena, Emanuela; Pepe, Veronica; Prezzavento, Orazio; Cacciatore, Ivana; Turkez, Hasan; Marrazzo, Agostino; Di Stefano, Antonio; Puglisi, Giovanni

    2017-07-01

    Nowadays sigma-1 receptors are considered as new therapeutic objectives for central nervous system neurodegenerative diseases. Among different molecules, alpha lipoic acid has been identified as a natural potent antioxidant drug, whose therapeutic efficacy is limited by its many drawbacks, such as fast metabolism, poor bioavailability and high physico-chemical instability. Alfa-lipoic acid derivatives have been recently developed demonstrating their neuroprotective activity and effectiveness in different types of oxidative stress. In this work, two derivatives containing an amide or an ester functional group with different lipophilicity, were selected for their important affinity for sigma-1 receptors. Herein, in order to improve the in vitro stability and antioxidant effectiveness of alpha-lipoic acid derivatives, we focused our efforts in the nanoencapsulation strategies. Aqueous-core nanocapsules for the delivery of the hydrophilic compound and nanostructured lipid carrier for the lipophilic derivative, were properly designed and prepared using a direct or inverse eco-friendly organic solvent-free procedure. All nanosystems were characterized in terms of mean size, polydispersity, stability, morphology, encapsulation efficiency and in vitro release profiles. In order to evaluate the nanocarriers biocompatibility and antioxidant effectiveness, in vitro biological studies (cell viability, total antioxidant capacity and total oxidative status) were developed on primary human whole blood cell cultures, on both unloaded and derivatives-loaded nanodevices. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Folate Receptor–Targeted Antioxidant Therapy Ameliorates Renal Ischemia–Reperfusion Injury

    Science.gov (United States)

    Knight, Sarah F.; Kundu, Kousik; Joseph, Giji; Dikalov, Sergey; Weiss, Daiana; Murthy, Niren

    2012-01-01

    Antioxidant therapy can protect against ischemic injury, but the inability to selectively target the kidney would require extremely high doses to achieve effective local concentrations of drug. Here, we developed a directed therapeutic that specifically targets an antioxidant to renal proximal tubule cells via the folate receptor. Because a local increase in superoxide contributes to renal ischemic injury, we created the folate-antioxidant conjugate 4-hydroxy-Tempo (tempol)-folate to target folate receptors, which are highly expressed in the proximal tubule. Dihydroethidium high-performance liquid chromatography demonstrated that conjugated tempol retained its efficacy to scavenge superoxide in proximal tubule cells. In a mouse model of renal ischemia-reperfusion injury, tempol-folate reduced renal superoxide levels more effectively than tempol alone. Furthermore, electron spin resonance revealed the successful targeting of the tempol-folate conjugate to the kidney and other tissues expressing folate receptors. Administration of tempol-folate protected the renal function of mice after ischemia-reperfusion injury and inhibited infiltration of macrophages. In conclusion, kidney-specific targeting of an antioxidant has therapeutic potential to prevent renal ischemic injury. Conjugation of other pharmaceuticals to folate may also facilitate the development of treatments for other kidney diseases. PMID:22282594

  14. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    Science.gov (United States)

    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.

  15. Implementation of nanoparticles in therapeutic radiation oncology

    Science.gov (United States)

    Beeler, Erik; Gabani, Prashant; Singh, Om V.

    2017-05-01

    Development and progress of cancer is a very complex disease process to comprehend because of the multiple changes in cellular physiology, pathology, and pathophysiology resulting from the numerous genetic changes from which cancer originates. As a result, most common treatments are not directed at the molecular level but rather at the tissue level. While personalized care is becoming an increasingly aim, the most common cancer treatments are restricted to chemotherapy, radiation, and surgery, each of which has a high likelihood of resulting in rather severe adverse side effects. For example, currently used radiation therapy does not discriminate between normal and cancerous cells and greatly relies on the external targeting of the radiation beams to specific cells and organs. Because of this, there is an immediate need for the development of new and innovative technologies that help to differentiate tumor cells and micrometastases from normal cells and facilitate the complete destruction of those cells. Recent advancements in nanoscience and nanotechnology have paved a way for the development of nanoparticles (NPs) as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery, and improve the therapeutic index of radiation and tumor response to the treatment. The application of NPs in radiation therapy has aimed to improve outcomes in radiation therapy by increasing therapeutic effect in tumors and reducing toxicity on normal tissues. Because NPs possess unique properties, such as preferential accumulation in tumors and minimal uptake in normal tissues, it makes them ideal for the delivery of radiotherapy. This review provides an overview of the recent development of NPs for carrying and delivering therapeutic radioisotopes for systemic radiation treatment for a variety of cancers in radiation oncology.

  16. [Latest advances in chronic pancreatitis].

    Science.gov (United States)

    Domínguez-Muñoz, J Enrique

    2014-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the prediction of the fibrosis degree of the gland, the evaluation of patients with asymptomatic hyperenzimemia, the medical and surgical treatment of abdominal pain and the knowledge of the natural history of the autoimmune pancreatitis. In patients with indetermined EUS findings of chronic pancreatitis, a new endoscopic ultrasound examination in the follow-up is of help to confirm or to exclude the disease. Smoking, number of relapses, results of pancreatic function tests and EUS findings allow predicting the degree of pancreatic fibrosis in patients with chronic pancreatitis. Antioxidant therapy has shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Development of intestinal bacterial overgrowth is frequent in patients with chronic pancreatitis, but its impact on symptoms is unknown and deserves further investigations. Finally, autoimmune pancreatitis relapses in about half of the patients with either type 1 or type 2 disease; relapses frequently occur within the first two years of follow-up. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  17. Effect of Antioxidants Supplementation on Aging and Longevity

    Science.gov (United States)

    Bartosz, Grzegorz

    2014-01-01

    If aging is due to or contributed by free radical reactions, as postulated by the free radical theory of aging, lifespan of organisms should be extended by administration of exogenous antioxidants. This paper reviews data on model organisms concerning the effects of exogenous antioxidants (antioxidant vitamins, lipoic acid, coenzyme Q, melatonin, resveratrol, curcumin, other polyphenols, and synthetic antioxidants including antioxidant nanoparticles) on the lifespan of model organisms. Mechanisms of effects of antioxidants, often due to indirect antioxidant action or to action not related to the antioxidant properties of the compounds administered, are discussed. The legitimacy of antioxidant supplementation in human is considered. PMID:24783202

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

    Science.gov (United States)

    Menciotti, Giulio; Borgarelli, Michele

    2017-09-26

    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.

  19. Antioxidants: Characterization, natural sources, extraction and analysis.

    Science.gov (United States)

    Oroian, Mircea; Escriche, Isabel

    2015-08-01

    Recently many review papers regarding antioxidants from different sources and different extraction and quantification procedures have been published. However none of them has all the information regarding antioxidants (chemistry, sources, extraction and quantification). This article tries to take a different perspective on antioxidants for the new researcher involved in this field. Antioxidants from fruit, vegetables and beverages play an important role in human health, for example preventing cancer and cardiovascular diseases, and lowering the incidence of different diseases. In this paper the main classes of antioxidants are presented: vitamins, carotenoids and polyphenols. Recently, many analytical methodologies involving diverse instrumental techniques have been developed for the extraction, separation, identification and quantification of these compounds. Antioxidants have been quantified by different researchers using one or more of these methods: in vivo, in vitro, electrochemical, chemiluminescent, electron spin resonance, chromatography, capillary electrophoresis, nuclear magnetic resonance, near infrared spectroscopy and mass spectrometry methods. Copyright © 2015. Published by Elsevier Ltd.

  20. Antioxidant Activity from Various Tomato Processing

    Directory of Open Access Journals (Sweden)

    Retno Sri Iswari

    2016-04-01

    Full Text Available Tomato is one of the high antioxidant potential vegetables. Nowadays, there are many techniques of tomato processings instead of fresh consumption, i.e. boiled, steamed, juiced and sauteed. Every treatment of cooking will influence the chemical compound inside the fruits and the body's nutrition intake. It is important to conduct the research on antioxidant compound especially lycopene, β-carotene, vitamin C, α-tocopherol, and its activity after processing. This research has been done using the experimental method. Tomatoes were cooked into six difference ways, and then it was extracted using the same procedure continued with antioxidant measurement. The research results showed that steaming had promoted the higher antioxidant numbers (lycopene. α-tocopherol, β-carotene and vitamin C and higher TCA and antioxidant activities in the tomatoes than other processings. It was indicated that steaming was the best way to enhance amount, capacity and activities of antioxidants of the tomatoes.

  1. In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles

    OpenAIRE

    Lucia Montenegro; Maria N. Modica; Loredana Salerno; Anna Maria Panico; Lucia Crascì; Giovanni Puglisi; Giuseppe Romeo

    2017-01-01

    Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL) and lipoic acid (IDELIP), to obtain a synergic effect; (2) loading of IDE, IDETRL, or IDELIP into solid lipid...

  2. Clinical applications of therapeutic phlebotomy

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-07-01

    Full Text Available Kyung Hee Kim,1 Ki Young Oh,2 1Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, 2Department of Physical Medicine and Rehabilitation, Soonchunhyang University, Cheonan Hospital, Cheonan, South Korea Abstract: Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. Keywords: therapeutic phlebotomy, hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, nonalcoholic fatty liver disease

  3. Inhibition of early upstream events in prodromal Alzheimer's disease by use of targeted antioxidants.

    Science.gov (United States)

    Prasad, Kedar N; Bondy, Stephen C

    2014-01-01

    A link between Alzheimer's disease (AD) and an excess presence of oxidant free radicals in the brain has frequently been reported. It is generally assumed that such oxidative stress and related cellular damage is caused by inflammatory changes in the brain and is consequent to amyloid deposition. This review makes the argument that elevated oxidative stress in AD is an early causal event in the initiation and advancement of this disease. Oxidative stress can be decreased by enhancing antioxidant enzymes through activation of the cytoplasmic transcriptional factor (Nrf2)/ARE (antioxidant response element) pathway, and by dietary and endogenous antioxidant chemicals. Reduction in the binding ability of Nrf2 to ARE lowers antioxidant enzyme levels. Decreased levels of Nrf2 and augmentation of oxidative stress in AD suggest that the ROS-dependent mechanism of activating the Nrf2/ARE pathway has become unresponsive. A combination of agents that can either activate the Nrf2-ARE pathway by ROS-independent mechanisms, or by acting directly as antioxidant chemicals, may be necessary to reduce oxidative stress in AD. Earlier shortcomings of using individual antioxidants may be due to consideration of antioxidants as pharmacological agents, ignoring the fact that individual antioxidants can be transmuted in the highly oxidant milieu that is present in AD. Interactions between various cellular compartments may require simultaneous examination of more than one agent. The clinical utility of such a more integrative method can reveal interactive effects such as those found in nutritional research and this can compensate for any mechanistic shortcomings of simultaneous testing of more than a single agent.

  4. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  5. Antioxidants and Other Micronutrients in Complementary Oncology

    OpenAIRE

    Gröber, Uwe

    2009-01-01

    Many patients being treated for cancer use micronutrient supplements, with the intention to complement their cancer treatment or help them cope with the therapy- and disease-associated side effects. The majority are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants are added to conventional cytotoxic therapies. However, it ...

  6. Antioxidants and embryo phenotype: is there experimental evidence for strong integration of the antioxidant system?

    Science.gov (United States)

    Possenti, Cristina Daniela; Karadas, Filiz; Colombo, Graziano; Caprioli, Manuela; Rubolini, Diego; Milzani, Aldo; Donne, Isabella Dalle; Saino, Nicola; Parolini, Marco

    2017-02-15

    Organisms have evolved complex defense systems against oxidative stress. Bird eggs contain maternally derived antioxidants that protect embryos from oxidative damage. The antioxidant system components are thought to be integrated, but few studies have analyzed the covariation between antioxidant concentrations, embryo 'oxidative status' and morphology. In addition, no study has tested the effects of experimental change in yolk antioxidant concentration on other antioxidants, on their reciprocal relationships and on their relationships with embryo oxidative status or growth, which are expected if antioxidants defenses are integrated. In yellow-legged gull ( Larus michahellis ) embryos, we analyzed the covariation between several antioxidants, markers of 'oxidative status' [total antioxidant capacity (TAC), concentration of pro-oxidants (TOS), lipid peroxidation (LPO) and protein carbonylation (PC)] in the yolk, liver and brain, and morphology. Yolk and liver antioxidant concentrations were positively correlated reciprocally and with embryo size, and positively predicted TAC but not oxidative status. TOS and LPO were positively correlated in the liver, while TAC and LPO were negatively correlated in the brain. Weak relationships existed between antioxidants and TOS, PC and LPO. The effects of antioxidants on oxidative status and morphology were non-synergistic. An experimental physiological increase in yolk vitamin E had very weak effects on the relationships between other antioxidants or oxidative status and vitamin E concentration, the concentration of other antioxidants or oxidative status; the covariation between other antioxidants and oxidative status, and relationships between morphology or oxidative status and other antioxidants, challenging the common wisdom of strong functional relationships among antioxidants, at least for embryos in the wild. © 2017. Published by The Company of Biologists Ltd.

  7. Recent Advances in Electrochemical Glycobiosensing

    OpenAIRE

    Sánchez-Pomales, Germarie; Zangmeister, Rebecca A.

    2011-01-01

    Biosensors based on electrochemical transduction mechanisms have recently made advances into the field of glycan analysis. These glyco-biosensors offer simple, rapid, sensitive, and economical approaches to the measurement need for rapid glycan analysis for biomarker detection, cancer and disease diagnostics, and bioprocess monitoring of therapeutic glycoproteins. Although the prevalent methods of glycan analysis (high-performance liquid chromatography, mass spectrometry, and nuclear magnet...

  8. Microwave-assisted extraction of Nigella sativa L. essential oil and evaluation of its antioxidant activity.

    Science.gov (United States)

    Abedi, Abdol-Samad; Rismanchi, Marjan; Shahdoostkhany, Mehrnoush; Mohammadi, Abdorreza; Mortazavian, Amir Mohammad

    2017-11-01

    It has been previously reported that the essential oil of Nigella sativa L. seeds and its major active component, thymoquinone (TQ), possess a broad variety of biological activities and therapeutic properties. In this work, microwave-assisted extraction (MAE) of the essential oil from Nigella sativa L. seeds and its antioxidant activity were studied. Response surface methodology based on central composite design was used to evaluate the effects of extraction time, irradiation power and moisture content on extraction yield and TQ content. Optimal parameters obtained by CCD and RSM were extraction time 30 min, irradiation power 450 W, and moisture content 50%. The extraction yield and TQ content of the essential oil were 0.33 and 20% under the optimum conditions, respectively. In contrast, extraction yield and TQ amount of oil obtained by hydrodistillation (HD) were 0.23 and 3.71%, respectively. The main constituents of the essential oil extracted by MAE and HD were p -cymene, TQ, α-thujene and longifolene, comprising more than 60% of total peak area. The antioxidant capacity of essential oils extracted by different methods were evaluated using 2,2-diphenyl-1-picrylhydrazyl and Ferric reducing antioxidant power assays, and compared with traditional antioxidants. The results showed that MAE method was a viable alternative to HD for the essential oil extraction from N. sativa seeds due to the excellent extraction efficiency, higher thymoquinone content, and stronger antioxidant activity.

  9. Oxidative Stress and Antioxidants in the Diagnosis and Therapy of Periodontitis

    Science.gov (United States)

    Tóthová, L'ubomíra; Celec, Peter

    2017-01-01

    Oxidative stress has been implicated in the pathogenesis of numerous diseases. However, large interventional studies with antioxidants failed to show benefits in the prevention or treatment of cardiovascular diseases, cancer, or diabetes mellitus. Numerous clinical studies have confirmed the association of oxidative stress markers and periodontitis. Technical and biological variability is high for most of the analyzed markers and none of them seems to be optimal for routine clinical use. In a research setting, analysis of a palette of oxidative stress markers is needed to cover lipid peroxidation, protein oxidation, and the antioxidant status. The source of reactive oxygen species and their role in the pathogenesis of periodontitis remains unclear. Interventional experiments indicate that oxidative stress might be more than just a simple consequence of the inflammation. Small studies have confirmed that some antioxidants could have therapeutic value at least as an addition to the standard non-surgical treatment of periodontitis. A clear evidence for the efficiency of antioxidant treatment in large patient cohorts is lacking. Potentially, because lowering of oxidative stress markers might be a secondary effect of anti-inflammatory or antibacterial agents. As the field of research of oxidative stress in periodontitis gains attraction and the number of relevant published papers is increasing a systematic overview of the conducted observational and interventional studies is needed. This review summarizes the currently available literature linking oxidative stress and periodontitis and points toward the potential of adjuvant antioxidant treatment, especially in cases where standard treatment fails to improve the periodontal status. PMID:29311982

  10. Antioxidant defense and oxidative stress in children with acute hepatitis A.

    Science.gov (United States)

    Popovic-Dragonjic, Lidija; Jovanovic, Maja; Vrbic, Miodrag; Konstantinovic, Ljiljana; Kostic, Velimir; Dragonjic, Ivan

    2011-01-01

    Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients. Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care. The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, β-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females). Plasma levels of reduced glutathione, β-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (Ppediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended.

  11. Gamma irradiation improves the antioxidant activity of Aloe vera (Aloe barbadensis miller) extracts

    International Nuclear Information System (INIS)

    Lee, Eun Mi; Bai, Hyoung-Woo; Lee, Seung Sik; Hong, Sung Hyun; Cho, Jae-Young; Byung, Yeoup Chung

    2012-01-01

    Aloe has been widely used in food products, pharmaceuticals, and cosmetics because of its aromatic and therapeutic properties. In the present study, the ethanolic extracts of aloe gel were gamma-irradiated from 10 to 100 kGy. After gamma irradiation, the color of the ethanolic extracts of aloe gel changed to red; this color persisted up to 40 kGy but disappeared above 50 kGy. Liquid chromatography/mass spectrometry analysis demonstrated the production of a new, unknown compound (m/z=132) after gamma irradiation of the ethanolic extracts of aloe gel. The amount of this unknown compound increased with increasing irradiation up to 80 kGy, and it was degraded at 100 kGy. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by the 1,1-diphenyl-2-picrylhydrazyl-radical scavenging capacity. The antioxidant activity of aloe extract was dramatically increased from 53.9% in the non-irradiated sample to 92.8% in the sample irradiated at 40 kGy. This strong antioxidant activity was retained even at 100 kGy. These results indicate that gamma irradiation of aloe extract can enhance its antioxidant activity through the formation of a new compound. Based on these results, increased antioxidant activity of aloe extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  12. Gamma irradiation improves the antioxidant activity of Aloe vera (Aloe barbadensis miller) extracts

    Science.gov (United States)

    Mi Lee, Eun; Bai, Hyoung-Woo; Sik Lee, Seung; Hyun Hong, Sung; Cho, Jae-Young; Yeoup Chung, Byung

    2012-08-01

    Aloe has been widely used in food products, pharmaceuticals, and cosmetics because of its aromatic and therapeutic properties. In the present study, the ethanolic extracts of aloe gel were gamma-irradiated from 10 to 100 kGy. After gamma irradiation, the color of the ethanolic extracts of aloe gel changed to red; this color persisted up to 40 kGy but disappeared above 50 kGy. Liquid chromatography/mass spectrometry analysis demonstrated the production of a new, unknown compound (m/z=132) after gamma irradiation of the ethanolic extracts of aloe gel. The amount of this unknown compound increased with increasing irradiation up to 80 kGy, and it was degraded at 100 kGy. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by the 1,1-diphenyl-2-picrylhydrazyl-radical scavenging capacity. The antioxidant activity of aloe extract was dramatically increased from 53.9% in the non-irradiated sample to 92.8% in the sample irradiated at 40 kGy. This strong antioxidant activity was retained even at 100 kGy. These results indicate that gamma irradiation of aloe extract can enhance its antioxidant activity through the formation of a new compound. Based on these results, increased antioxidant activity of aloe extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  13. In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits

    Science.gov (United States)

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2017-02-01

    To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20-50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development.

  14. Pomegranate peel extract decreases small intestine lipid peroxidation by enhancing activities of major antioxidant enzymes.

    Science.gov (United States)

    Al-Gubory, Kaïs H; Blachier, François; Faure, Patrice; Garrel, Catherine

    2016-08-01

    Pomegranate peel extract (PPE) contains several compounds with antioxidative properties. PPE added to foods may interact with endogenous antioxidants and promote health. However, little is known about the biochemical mechanisms by which PPE exerts their actions on tissues of biological systems in vivo. The purpose of this study was to determine the effects of PPE on activities of antioxidant enzymes. Mice were used to investigate the effects of PPE on plasma levels of malondialdehyde (MDA), tissue MDA content and activities of superoxide dismutase 1 (SOD1), SOD2 and glutathione peroxidase (GPX) in the small intestine, liver and skeletal muscle - different tissues involved in the digestion, absorption and metabolism of dietary nutrients. Control mice were fed a standard diet, whereas treated mice were fed for 40 days with the standard diet containing 5% or 10% PPE. Mice fed the 10% PPE diet exhibited lower plasma MDA concentrations, reduced content of MDA in the small intestine and liver and higher levels of SOD1 and GPX activities in the small intestine compared to mice fed the control diet. These findings demonstrate that intake of PPE in diet attenuates small intestine lipid peroxidation and strengthens the first line of small intestine antioxidant defense by enhancing enzymatic antioxidative pathways. PPE is worthy of further study as a therapeutic approach to prevent peroxidative stress-induced gut pathogenesis. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  15. Oxidative Stress and Antioxidants in the Diagnosis and Therapy of Periodontitis

    Directory of Open Access Journals (Sweden)

    L'ubomíra Tóthová

    2017-12-01

    Full Text Available Oxidative stress has been implicated in the pathogenesis of numerous diseases. However, large interventional studies with antioxidants failed to show benefits in the prevention or treatment of cardiovascular diseases, cancer, or diabetes mellitus. Numerous clinical studies have confirmed the association of oxidative stress markers and periodontitis. Technical and biological variability is high for most of the analyzed markers and none of them seems to be optimal for routine clinical use. In a research setting, analysis of a palette of oxidative stress markers is needed to cover lipid peroxidation, protein oxidation, and the antioxidant status. The source of reactive oxygen species and their role in the pathogenesis of periodontitis remains unclear. Interventional experiments indicate that oxidative stress might be more than just a simple consequence of the inflammation. Small studies have confirmed that some antioxidants could have therapeutic value at least as an addition to the standard non-surgical treatment of periodontitis. A clear evidence for the efficiency of antioxidant treatment in large patient cohorts is lacking. Potentially, because lowering of oxidative stress markers might be a secondary effect of anti-inflammatory or antibacterial agents. As the field of research of oxidative stress in periodontitis gains attraction and the number of relevant published papers is increasing a systematic overview of the conducted observational and interventional studies is needed. This review summarizes the currently available literature linking oxidative stress and periodontitis and points toward the potential of adjuvant antioxidant treatment, especially in cases where standard treatment fails to improve the periodontal status.

  16. In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles.

    Science.gov (United States)

    Montenegro, Lucia; Modica, Maria N; Salerno, Loredana; Panico, Anna Maria; Crascì, Lucia; Puglisi, Giovanni; Romeo, Giuseppe

    2017-05-27

    Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL) and lipoic acid (IDELIP), to obtain a synergic effect; (2) loading of IDE, IDETRL, or IDELIP into solid lipid nanoparticles (SLN) to improve IDE and its esters' water solubility while increasing and prolonging their antioxidant activity. IDE and its derivatives loaded SLN showed good physico-chemical and technological properties (spherical shape, mean particle sizes 23-25 nm, single peak in the size distribution, ζ potential values -1.76/-2.89 mV, and good stability at room temperature). In vitro antioxidant activity of these SLN was evaluated in comparison with free drugs by means of oxygen radical absorbance capacity (ORAC) test. IDETRL and IDELIP showed a greater antioxidant activity than IDE and encapsulation of IDE and its derivatives into SLN was able to prolong their antioxidant activity. These results suggest that loading IDETRL and IDELIP into SLN could be a useful strategy to improve IDE efficacy.

  17. In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Lucia Montenegro

    2017-05-01

    Full Text Available Idebenone (IDE has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1 synthesis of IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL and lipoic acid (IDELIP, to obtain a synergic effect; (2 loading of IDE, IDETRL, or IDELIP into solid lipid nanoparticles (SLN to improve IDE and its esters’ water solubility while increasing and prolonging their antioxidant activity. IDE and its derivatives loaded SLN showed good physico-chemical and technological properties (spherical shape, mean particle sizes 23–25 nm, single peak in the size distribution, ζ potential values −1.76/−2.89 mV, and good stability at room temperature. In vitro antioxidant activity of these SLN was evaluated in comparison with free drugs by means of oxygen radical absorbance capacity (ORAC test. IDETRL and IDELIP showed a greater antioxidant activity than IDE and encapsulation of IDE and its derivatives into SLN was able to prolong their antioxidant activity. These results suggest that loading IDETRL and IDELIP into SLN could be a useful strategy to improve IDE efficacy.

  18. Grafting functional antioxidants on highly crosslinked polyethylene

    Science.gov (United States)

    Al-Malaika, S.; Riasat, S.; Lewucha, C.

    2016-05-01

    The problem of interference of antioxidants, such as hindered phenols, with peroxide-initiated crosslinking of polyethylene was addressed through the use of functional (reactive) graftable antioxidants (g-AO). Reactive derivatives of hindered phenol and hindered amine antioxidants were synthesised, characterised and used to investigate their grafting reactions in high density polyethylene; both non-crosslinked (PE) and highly peroxide-crosslinked (PEXa). Assessment of the extent of in-situ grafting of the antioxidants, their retention after exhaustive solvent extraction in PE and PEXa, and the stabilising performance of the grafted antioxidants (g-AO) in the polymer were examined and benchmarked against conventionally stabilised crosslinked & non-crosslinked polyethylene. It was shown that the functional antioxidants graft to a high extent in PEXa, and that the level of interference of the g-AOs with the polymer crosslinking process was minimal compared to that of conventional antioxidants which bear the same antioxidant function. The much higher level of retention of the g-AOs in PEXa after exhaustive solvent extraction, compared to that of the corresponding conventional antioxidants, accounts for their superior long-term thermal stabilising performance under severe extractive conditions.

  19. Antioxidant Protection in Blood against Ionising Radiation

    International Nuclear Information System (INIS)

    Bognar, G.; Meszaros, G.; Koteles, G. J.

    2001-01-01

    Full text: The quantities of the antioxidants in the human blood are important indicators of health status. The routine determinations of activities/capacities of antioxidant compounds would be of great importance in assessing individual sensitivities against oxidative effects. We have investigated the sensitivities of those antioxidant elements against various doses of ionising radiation tested by the RANDOX assays. Our results show dose-dependent decreases of antioxidant activities caused by the different doses. The total antioxidant status value linearly decreased up to 1 Gy, but further increase of dose (2 Gy) did not influence the respective values although the test system still indicated their presence. It means that the human blood retains 60-70% of its total antioxidant capacity. Radiation induced alterations of the antioxidant enzymes: glutathione peroxidase and superoxide dismutase have been also investigated. The activities of glutathione peroxidase and superoxide dismutase decreased linearly upon the effects of various doses of ionising radiation till 1 Gy. Between 1 and 2 Gy only further mild decreases could be detected. In this case the human blood retained 40-60% of these two antioxidant enzymes. These observations suggest either the limited response of antioxidant system against ionising radiation, or the existence of protection system of various reactabilities. (author)

  20. Antioxidants and prevention of gastrointestinal cancers.

    Science.gov (United States)

    Williams, Christina D

    2013-03-01

    Gastrointestinal cancers account for 20% of all incident cancers in the United States. Much work has been done to understand the role dietary factors play in the prevention of gastrointestinal cancers, yet evidence regarding the potential preventive effect of antioxidants is conflicting. This review highlights the recent studies investigating the associations between dietary antioxidants and cancers of the gastrointestinal tract. In-vitro and in-vivo studies in animals continue to support the hypothesis that antioxidants reduce the risk of gastrointestinal cancers. Results in human populations are not as supportive. Antioxidant nutrients and fruits and vegetables do not seem to confer protection against colorectal cancer, and certain antioxidants were found to increase the risk of distal colon cancer. Individual antioxidants also do not help prevent pancreatic cancer. Total antioxidant intake and plant-based foods seem promising for stomach cancer prevention, while vitamin C lowers the risk of esophageal cancer. Preventive effects for stomach and esophageal cancers were often limited to or stronger in smokers. Evidence is scarce regarding antioxidants and liver cancer. Antioxidants do not aid in the prevention of gastrointestinal cancers in the general population; however, they may act as chemopreventive agents for stomach and esophageal cancers, especially in high-risk populations.